Contrast-enhanced ultrasonography as an adjunctive method to ICG lymphography for functional lymphaticovenous anastomosis.

BACKGROUND AND OBJECTIVES: Indocyanine green (ICG) lymphography is the reference standard for evaluating lymphedema stage and identifying lymphatic vessels. However, the penetration depth was limited to 1-2 cm from the skin surface. This prospective study compares clinical outcomes following lymphaticovenous anastomoses (LVA) in patients with upper and lower limb lymphedema using contrast-enhanced ultrasonography (CEUS) with ICG as a preoperative imaging modality. METHODS: Under general anesthesia, Sonazoid® was injected subcutaneously to visualize functional lymphatic channels via CEUS. We analyzed the changes in limb circumference and inter-limb ratio (ILR) using bioimpedance to measure electrical resistance between the CEUS plus ICG group and the ICG-only group to see the effect of CEUS-assisted LVA. RESULTS: No significant demographic differences existed between the two groups (CEUS plus ICG group vs. ICG-only group). The ILR decrease of the Z1 value measured using bioimpedance was statistically significant (p = 0.042 for the upper limb, p = 0.002 for the lower limb)- CONCLUSIONS: CEUS allowed us to identify deep-lying, functional, and large lymphatic channels. In conclusion, the combination of CEUS and ICG for identifying lymphatic channels has the potential to lead to a more functional lymphovenous anastomosis.

In Vivo Dynamic and Static Analysis of Lymphatic Dysfunction in Lymphedema Using Near-Infrared Fluorescence Indocyanine Green Lymphangiography.

BACKGROUND: Near-infrared fluorescence indocyanine green lymphangiography, a primary modality for detecting lymphedema, which is a disease due to lymphatic obstruction, enables real-time observations of lymphatics and reveals not only the spatial distribution of drainage (static analysis) but also information on the lymphatic contraction (dynamic analysis). METHODS: We have produced total lymphatic obstruction in the upper limbs of 18 Sprague-Dawley rats through the dissection of proximal (brachial and axillary) lymph nodes and 20-Gy radiation (dissection limbs). After the model formation for 1 week, 9 animal models were observed for 6 weeks using near-infrared fluorescence indocyanine green lymphangiography by injecting 6-µL ICG-BSA (indocyanine green-bovine serum albumin) solution of 20-µg/mL concentration. The drainage pattern and leakage of lymph fluid were evaluated and time-domain signals of lymphatic contraction were observed in the distal lymphatic vessels. The obtained signals were converted to frequency-domain spectrums using signal processing. RESULTS: The results of both static and dynamic analyses proved to be effective in accurately identifying the extent of lymphatic disruption in the dissection limbs. The static analysis showed abnormal drainage patterns and increased leakage of lymph fluid to the periphery of the vessels compared with the control (normal) limbs. Meanwhile, the waveforms were changed and the contractile signal frequency increased by 58% in the dynamic analysis. Specifically, our findings revealed that regular lymphatic contractions, observed at a frequency range of 0.08 to 0.13 Hz in the control limbs, were absent in the dissection limbs. The contractile regularity was not fully restored for the follow-up period, indicating a persistent lymphatic obstruction. CONCLUSIONS: The dynamic analysis could detect the abnormalities of lymphatic circulation by observing the characteristics of signals, and it provided additional evaluation indicators that cannot be provided by the static analysis. Our findings may be useful for the early detection of the circulation problem as a functional evaluation indicator of the lymphatic system.

Advances in lymphedema: An under-recognized disease with a hopeful future for patients.

Lymphedema has traditionally been underappreciated by the healthcare community. Understanding of the underlying pathophysiology and treatments beyond compression have been limited until recently. Increased investigation has demonstrated the key role of inflammation and resultant fibrosis and adipose deposition leading to the clinical sequelae and associated reduction in quality of life with lymphedema. New imaging techniques including magnetic resonance imaging (MRI), indocyanine green lymphography, and high-frequency ultrasound offer improved resolution and understanding of lymphatic anatomy and flow. Nonsurgical therapy with compression, exercise, and weight loss remains the mainstay of therapy, but growing surgical options show promise. Physiologic procedures (lymphovenous anastomosis and vascularized lymph node transfers) improve lymphatic flow in the diseased limb and may reduce edema and the burden of compression. Debulking, primarily with liposuction to remove the adipose deposition that has accumulated, results in a dramatic decrease in limb girth in appropriately selected patients. Though early, there are also exciting developments of potential therapeutic targets tackling the underlying drivers of the disease. Multidisciplinary teams have developed to offer the full breadth of evaluation and current management, but the development of a greater understanding and availability of therapies is needed to ensure patients with lymphedema have greater opportunity for optimal care.

Lymphedema after saphenous harvesting for coronary artery bypass surgery: case report and literature review.

Different causes have been described for secondary lymphedema as reported in this article. A 75-year-old man was diagnosed with lymphedema about one decade after saphenous harvesting for coronary artery bypass surgery. It took two years for him to find out his diagnosis and receive the proper treatment. After standard complete decongestive therapy, his volume and pain decreased and his quality of life was improved, especially its physical aspect. It is important to recognize the possibility of lymphedema development after saphenous harvesting among patients undergoing coronary artery bypass surgery to prevent significant disturbance of quality of life with timely management.

Digital Volumetric Measurements Based on 3D Scans of the Lower Limb: A Valid and Reproducible Method for Evaluation in Lymphedema Therapy.

BACKGROUND: Exact quantification of volumetric changes of the extremities is difficult and often error-prone. The aim of this study was to establish a standardized method based on 3-dimensional (3D) scans. Furthermore, this study tests the method in terms of reproducibility and evaluates volume changes after surgical therapy in patients suffering from lymphedema on the lower extremity. METHODS: 3D scans of the lower limb were performed with a mobile 3D scanner; "repeatability" and "interobserver reliability" of digital volumetry were tested. Furthermore, the method was applied on 31 patients suffering from chronic lymphedema. RESULTS: Calculations of repeatability of the volume based on 20 3D scans of the same lower leg showed a mean volume of 2.488 ± 0.011 liters (range: 2.470-2.510). The mean volume of the different examiners did not differ significantly (F(2,18) = 1.579, P = 0.233). The paired t-test showed a significant mean volume decrease of 375 mL (95% confidence interval = 245/505 mL) between pretreatment and post-treatment (t (30) = 5.892, P < 0.001). CONCLUSIONS: 3D volumetry is a noninvasive, easy, and quick method to assess volume changes of the lower leg. Other than the low costs, it is reproducible and precise and therefore ideal for evolution of therapy in lymphedema.

Preoperative photoacoustic versus indocyanine green lymphography in lymphaticovenular anastomosis outcomes for lower extremity lymphedema: A pilot study.

BACKGROUND: Identification of the proper lymphatics is important for successful lymphaticovenular anastomosis (LVA) for lymphedema; however, visualization of lymphatic vessels is challenging. Photoacoustic lymphangiography (PAL) can help visualize lymphatics more clearly than other modalities. Therefore, we investigated the usefulness of PAL and determined whether the clear and three-dimensional image of PAL affects LVA outcomes. METHODS: We recruited 22 female patients with lower extremity lymphedema. The operative time, number of incisions, number of anastomoses, lymphatic vessel detection rate (number of functional lymphatics identified during the operation/number of incisions), and limb volume changes preoperatively and 3 months postoperatively were compared retrospectively. The patients were divided according to whether PAL was performed or not, and results were compared between those undergoing PAL (PAL group; n = 10) and those who did not (near-infrared fluorescence [NIRF] group, n = 12). RESULTS: The mean age of the patients was 55.9 ± 15.1 years in the PAL group and 50.7 ± 14.9 years in the NIRF group. One patient in the PAL group and three in the NIRF group had primary lymphedema. Eighteen patients (PAL group, nine; and NIRF group, nine) had secondary lymphedema. Based on preoperative evaluation using the International Society of Lymphology (ISL) classification, eight patients were determined to be in stage 2 and two patients in late stage 2 in the PAL group. In contrast, in the NIRF group, one patient was determined to be in stage 0, three patients each in stage 1 and stage 2, and five patients in late stage 2. Lymphatic vessel detection rates were 93% (42 LVAs and 45 incisions) and 83% (50 LVAs and 60 incisions) in the groups with and without PAL, respectively (p = 0.42). Limb volume change was evaluated in five limbs of four patients and in seven limbs of five patients in the PAL and NIRF groups as 336.6 ± 203.6 mL (5.90% ± 3.27%) and 52.9 ± 260.7 mL (0.71% ± 4.27%), respectively. The PAL group showed a significant volume reduction. (p = .038). CONCLUSIONS: Detection of functional lymphatic vessels on PAL is useful for treating LVA.

Superficial and functional imaging of the tricipital lymphatic pathway: a modern reintroduction.

PURPOSE: The tricipital, or Caplan's, lymphatic pathway has been previously identified in cadavers and described as a potential compensatory pathway for lymphatic drainage of the upper extremity, as it may drain lymphatic fluid directly to the scapular lymph nodes, avoiding the axillary lymph node groups. The aim of this study was to map the anatomy of the tricipital pathway in vivo in patients without lymphatic disease. METHODS: A retrospective review was performed to identify patients with unilateral breast cancer undergoing preoperative Indocyanine green (ICG) lymphography prior to axillary lymph node dissection from May 2021 through January 2022. Exclusion criteria were evidence or known history of upper extremity lymphedema or non-linear channels visualized on ICG. Demographic, oncologic, and ICG imaging data were extracted from a Lymphatic Surgery Database. The primary outcome of this study was the presence and absence of the tricipital pathway. The secondary outcome was major anatomical variations among those with a tricipital pathway. RESULTS: Thirty patients underwent preoperative ICG lymphography in the study period. The tricipital pathway was visualized in the posterior upper arm in 90% of patients. In 63% of patients, the pathway had a functional connection to the forearm (long bundle variant) and in 27%, the pathway was isolated to the upper arm without a connection to the forearm (short bundle variant). In those with a long bundle, the contribution was predominantly from the posterior ulnar lymphosome. Anatomic destinations of the tricipital pathway included the deltotricipital groove and the medial upper arm channel, which drains to the axilla. CONCLUSION: When present, the tricipital pathway coursed along the posterior upper arm with variability in its connections to the forearm distally, and the torso proximally. Long-term follow-up studies will help determine the significance of these anatomic variations in terms of individual risk of lymphedema after axillary nodal dissection.

Subcutaneous Adipose Tissue Edema in Lipedema Revealed by Noninvasive 3T MR Lymphangiography.

BACKGROUND: Lipedema exhibits excessive lower-extremity subcutaneous adipose tissue (SAT) deposition, which is frequently misidentified as obesity until lymphedema presents. MR lymphangiography may have relevance to distinguish lipedema from obesity or lymphedema. HYPOTHESIS: Hyperintensity profiles on 3T MR lymphangiography can identify distinct features consistent with SAT edema in participants with lipedema. STUDY TYPE: Prospective cross-sectional study. SUBJECTS: Participants (48 females, matched for age [mean = 44.8 years]) with lipedema (n = 14), lipedema with lymphedema (LWL, n = 12), cancer treatment-related lymphedema (lymphedema, n = 8), and controls without these conditions (n = 14). FIELD STRENGTH/SEQUENCE: 3T MR lymphangiography (nontracer 3D turbo-spin-echo). ASSESSMENT: Review of lymphangiograms in lower extremities by three radiologists was performed independently. Spatial patterns of hyperintense signal within the SAT were scored for extravascular (focal, diffuse, or not apparent) and vascular (linear, dilated, or not apparent) image features. STATISTICAL TESTS: Interreader reliability was computed using Fleiss Kappa. Fisher's exact test was used to evaluate the proportion of image features between study groups. Multinomial logistic regression was used to assess the relationship between image features and study groups. The odds ratio (OR) and 95% confidence interval (CI) of SAT extravascular and vascular features was reported in groups compared to lipedema. The threshold of statistical significance was P < 0.05. RESULTS: Reliable agreement was demonstrated between three independent, blinded reviewers (P < 0.001). The frequency of SAT hyperintensities in participants with lipedema (36% focal, 36% diffuse), LWL (42% focal, 33% diffuse), lymphedema (62% focal, 38% diffuse), and controls (43% focal, 0% diffuse) was significantly distinct. Compared with lipedema, SAT hyperintensities were less frequent in controls (focal: OR = 0.63, CI = 0.11-3.41; diffuse: OR = 0.05, CI = 0.00-1.27), similar in LWL (focal: OR = 1.29, CI = 0.19-8.89; diffuse: OR = 1.05, CI = 0.15-7.61), and more frequent in lymphedema (focal: OR = 9.00, CI = 0.30-274.12; diffuse: OR = 5.73, CI = 0.18-186.84). DATA CONCLUSION: Noninvasive MR lymphangiography identifies distinct signal patterns indicating SAT edema and lymphatic load in participants with lipedema. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Advances in Lymphedema.

Lymphedema is a common, complex, and inexplicably underappreciated human disease. Despite a history of relative neglect by health care providers and by governmental health care agencies, the last decade has seen an explosive growth of insights into, and approaches to, the problem of human lymphedema. The current review highlights the significant advances that have occurred in the investigative and clinical approaches to lymphedema, particularly over the last decade. This review summarizes the progress that has been attained in the realms of genetics, lymphatic imaging, and lymphatic surgery. Newer molecular insights are explored, along with their relationship to future molecular therapeutics. Growing insights into the relationships among lymphedema, obesity, and other comorbidities are important to consider in current and future responses to patients with lymphedema.

Body image and cancer-related lymphoedema: A systematic review.

OBJECTIVE: Cancer-related lymphoedema is a common side effect of cancer, affecting 24%-49% of people with cancer. Body image contributes to the well-being of individuals with this condition. This systematic review aimed to explore, for the first time, the state of the science concerning body image in cancer-related lymphoedema, including how body image is measured and variables associated with body image concerns. METHODS: Six databases were systematically searched for peer-reviewed articles describing empirical quantitative studies where body image was measured with a reliable and valid measurement tool in adults with cancer-related lymphoedema. RESULTS: Nine studies with 977 participants were included. The studies involved individuals who had experienced breast, head and neck, melanoma, and urogenital cancers and developed lymphoedema. There was considerable heterogeneity in body image measures used, precluding meta-analysis. The following variables were associated with increased body image concern: higher body integrity beliefs, experience of physical changes (e.g. pain) and differences in sensation and function, including changes in appearance related thoughts, feelings and emotions. Several studies described behavioural and psychological interventions which positively impacted body image outcomes in individuals with lymphoedema relating to specific cancers. CONCLUSION: Regular screening for body image concerns could encourage more positive body image awareness in individuals with cancer-related lymphoedema and lessen some of its associated negative consequences. Future longitudinal and individual differences research in this area is important to inform intervention development. There is also need for a more standardised approach to the study and measurement of body image in people with cancer-related lymphoedema.

Deep learning for standardized, MRI-based quantification of subcutaneous and subfascial tissue volume for patients with lipedema and lymphedema.

OBJECTIVES: To contribute to a more in-depth assessment of shape, volume, and asymmetry of the lower extremities in patients with lipedema or lymphedema utilizing volume information from MR imaging. METHODS: A deep learning (DL) pipeline was developed including (i) localization of anatomical landmarks (femoral heads, symphysis, knees, ankles) and (ii) quality-assured tissue segmentation to enable standardized quantification of subcutaneous (SCT) and subfascial tissue (SFT) volumes. The retrospectively derived dataset for method development consisted of 45 patients (42 female, 44.2 ± 14.8 years) who underwent clinical 3D DIXON MR-lymphangiography examinations of the lower extremities. Five-fold cross-validated training was performed on 16,573 axial slices from 40 patients and testing on 2187 axial slices from 5 patients. For landmark detection, two EfficientNet-B1 convolutional neural networks (CNNs) were applied in an ensemble. One determines the relative foot-head position of each axial slice with respect to the landmarks by regression, the other identifies all landmarks in coronal reconstructed slices using keypoint detection. After landmark detection, segmentation of SCT and SFT was performed on axial slices employing a U-Net architecture with EfficientNet-B1 as encoder. Finally, the determined landmarks were used for standardized analysis and visualization of tissue volume, distribution, and symmetry, independent of leg length, slice thickness, and patient position. RESULTS: Excellent test results were observed for landmark detection (z-deviation = 4.5 ± 3.1 mm) and segmentation (Dice score: SCT = 0.989 ± 0.004, SFT = 0.994 ± 0.002). CONCLUSIONS: The proposed DL pipeline allows for standardized analysis of tissue volume and distribution and may assist in diagnosis of lipedema and lymphedema or monitoring of conservative and surgical treatments. KEY POINTS: • Efficient use of volume information that MRI inherently provides can be extracted automatically by deep learning and enables in-depth assessment of tissue volumes in lipedema and lymphedema. • The deep learning pipeline consisting of body part regression, keypoint detection, and quality-assured tissue segmentation provides detailed information about the volume, distribution, and asymmetry of lower extremity tissues, independent of leg length, slice thickness, and patient position.

Measurement of lymphatic vessel depth using photoacoustic imaging.

OBJECTIVES: Information regarding the depth of lymphatic vessel is important for lymphatic surgeons because rapid identification of functional lymphatic vessels and veins is necessary to perform good lymphaticovenular anastomosis, which is a surgical procedure for lymphedema cases. Photoacoustic lymphangiography (PAL) may be useful for such identification because it allows the assessment of the depth of lymphatic vessels. Thus, we aimed to measure the lymphatic vessel depth using images obtained by PAL. METHODS: This study included healthy individuals and patients with lymphedema. In all participants, indocyanine green dissolved in dextrose was injected subcutaneously into the first and fourth webs of the foot and the lateral malleolus, and PAL was performed on the medial side of the lower leg. The lymphatic vessel depth was measured from the ankle joint, 10 cm above the medial malleolus, and 20 cm above the medial malleolus on PAL in the cross-sectional view and was compared between the participant groups. RESULTS: The healthy group (mean age, 43.3 ± 12.9 years) included 21 limbs of 4 male and 16 female healthy individuals (bilateral limbs of 1 patient were considered). The lymphedema group (mean age, 62.0 ± 11.7 years) included 17 limbs of 3 male and 14 female patients with lymphedema. The average lymphatic vessel depths from the ankle joint, 10 cm above the medial malleolus, and 20 cm above the medial malleolus were 2.6, 4.7, and 5.6 mm in the healthy group and 3.6, 7.3, and 7.4 mm in the lymphedema group, respectively. Lymphatic vessels were significantly deeper in the lymphedema group than in the healthy group at all measurement locations. CONCLUSIONS: Using PAL, we determined the lymphatic vessel depth in living bodies. By searching for the lymphatic vessels based on our findings, even surgeons who are relatively inexperienced with lymphatic surgery may be able to identify functional lymphatic vessels more efficiently.

MRI-based volume measurement methods for staging primary lower extremity lymphedema: a single-center study of asymmetric volume difference-a diagnostic study.

BACKGROUND: Lower extremity lymphedema (LEL) staging is mainly assessed by systems that solely depend on physical examinations and lack quantitative assessment based on modern imaging. OBJECTIVE: To explore the value of MRI-based asymmetric volume measurements in the clinical staging of primary LEL. METHODS: 92 patients with unilateral primary LEL underwent MRI examinations to determine the volume of the mid-calf (Vcl) calculated using the clinical dermatome method as well as the total volume (Vmri), musculoskeletal volume (VM), and subcutaneous volume (VS) volume of the middle calves. The difference between Vmri (DVmri) and VS (DVS) of the affected and unaffected calves was obtained and defined as the asymmetric volume difference. Meanwhile, the volume of the mid-calf (Vcl) and the difference in volume (DVcl) were calculated using the clinical circumferential method. The relationship between the asymmetric volume difference and clinical staging was then evaluated. Interobserver consistency was assessed through the intraclass correlation coefficient (ICC). Volume comparisons between the three groups were performed using the one-way analysis of variance (ANOVA) or the Kruskal-Wallis test. Spearman's correlation was used to assess volume and clinical stage correlation. The receiver operating characteristic (ROC) curve was used to evaluate the value of asymmetric volume difference for clinical staging. RESULTS: The asymmetric volume difference was statistically significant in stage I compared to stages II and III (p < 0.05). The asymmetric volume difference (DVmri: r = 0.753; DVS: r = 0.759) correlated more with the clinical stage than the affected Vcl (r = 0.581), Vmri (r = 0.628), VS (r = 0.743), and DVcl (r = 0.718). The area under the ROC curve (AUC) for identifying the clinical stage by the asymmetric volume difference was greater than that for the affected Vcl, Vmri, VS, and DVcl, with DVS (AUC = 0.951) having the largest area under the curve to distinguish between stages I and II. CONCLUSION: MRI-based asymmetric volume difference is an adjunctive measure for LEL clinical staging with good reproducibility. DVS could be the best indicator for differentiating between stages I and II of primary LEL.

Fluid Distribution Patterns in Early-Stage Upper Extremity Lymphedema.

INTRODUCTION: Magnetic resonance imaging (MRI) stage 1 (early stage) upper extremity lymphedema is characterized by fluid infiltration in the subcutaneous tissues that does not exceed 50% of the extremity circumference at any level. The spatial fluid distribution in these cases has not been detailed and may be important to help determine the presence and location of compensatory lymphatic channels. The aim of this study is to determine whether there was a pattern of distribution of fluid infiltration in patients with early-stage lymphedema that could correspond to known lymphatic pathways in the upper extremity. METHODS: A retrospective review identified all patients with MRI stage 1 upper extremity lymphedema who were evaluated at a single lymphatic center. Using a standardized scoring system, a radiologist graded the severity of fluid infiltration at 18 anatomical locations. A cumulative spatial histogram was then created to map out regions where fluid accumulation occurred most and least frequently. RESULTS: Eleven patients with MRI stage 1 upper extremity lymphedema were identified between January 2017 and January 2022. The mean age was 58 years and the mean BMI was 30 m/kg2. One patient had primary lymphedema and the remaining 10 had secondary lymphedema. The forearm was affected in nine cases, and fluid infiltration was predominantly concentrated along the ulnar aspect, followed by the volar aspect, while the radial aspect was completely spared. Within the upper arm, fluid was primarily concentrated distally and posteriorly, and occasionally medially. CONCLUSIONS: In patients with early-stage lymphedema, fluid infiltration is concentrated along the ulnar forearm and the posterior distal upper arm, which aligns with the tricipital lymphatic pathway. There is also sparing of fluid accumulation along the radial forearm in these patients, suggesting a more robust lymphatic drainage along this region, possibly due to a connection to the lateral upper arm pathway.

Lymphatic refill in ultrasound and lymphatic washout after lymphaticovenous anastomosis.

BACKGROUND: Lymphaticovenous anastomosis (LVA) drains lymph accumulated in the lymphatic vessels into the veins (lymphatic washout). A method to identify the ideal lymphatic vessels to achieve washout has not been established. This study examined the relationship between lymphatic washout, lymphatic ultrasonographic findings, and surgical outcomes. METHODS: We reviewed consecutive patients who underwent LVA for lower limb lymphedema between September 2020 and March 2021. Patients who lacked data were excluded. Preoperative ultrasonography was performed to measure the lymphatic diameter. After the probe was pressed against the skin and released, the reaction of the lymphatic vessels was classified as either refilled, crushed, undecidable, or solid. Intraoperatively, whether lymphatic washout was observed or not, was recorded and compared to preoperative findings using the chi-square test. In 54 limbs from 32 patients, the total number of LVA, number of anastomoses with washout, number of refills detected by ultrasound, and severity of lymphedema were compared with the surgical result (postoperative limb volume change) by multiple regression analysis (49 limbs whose pre-or postoperative circumference data were lacking or who underwent intensive compression therapy postoperatively were excluded). RESULTS: Sixty-five patients were reviewed. After excluding six patients with missing data, 59 patients (103 limbs) were included. The median patient age was 63 years (interquartile range, 51-76 years). We performed LVA at 217 sites (mean, 2.1 anastomoses per limb). "Refilled" lymphatics were observed at 156 sites (71.6%) and significantly thicker than those classified as "undecidable" (p = .020 in the lower leg and p < .001 in the thigh). In the thigh, "refilled" lymphatics had a higher rate of a washout than those classified as "undecidable." In Pearson's correlation coefficient for the surgical result, as the number of washout positive LVA increased, the limb volume tended to decrease postoperatively (correlation coefficient: -0.25). However, multiple regression analysis did not identify any factors that significantly affected the surgical outcomes. CONCLUSION: "Refilled" lymphatic vessels had a higher rate of intraoperative lymphatic washout after anastomosis.

Comparative Analysis of Preoperative High Frequency Color Doppler Ultrasound versus MR Lymphangiography versus ICG Lymphography of Lymphatic Vessels in Lymphovenous Anastomosis.

BACKGROUND: Despite the extensive use of various imaging modalities, there is limited literature on comparing the reliability between indocyanine green (ICG) lymphography, MR Lymphangiogram (MRL), and high frequency color Doppler ultrasound (HFCDU) to identify lymphatic vessels. METHOD: In this study of 124 patients, the correlation between preoperative image findings to the actual lymphatic vessel leading to lymphovenous anastomosis (LVA) was evaluated. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and simple detection were calculated. Subgroup analysis was also performed according to the severity of lymphedema. RESULTS: Total of 328 LVAs were performed. The HFCDU overall had significantly higher sensitivity for identifying lymphatic vessels (99%) over MRL (83.5%) and ICG lymphography (82.3%)(p < 0.0001). Both ICG lymphography and HFCDU had 100% specificity and PPV. The NPV was 3.6%, 6.5% and 57.1% respectively for MRL, ICG lymphography, and HFCDU. All modalities showed high sensitivity for early stage 2 lymphedema while HFCDU showed a significantly higher sensitivity for late stage 2 (MRL:79.7%, ICG:83.1%, HFCDU:97%) and stage 3 (MRL:79.7%, ICG:79.7%, HFCDU:100%) over the other two modalities (p < 0.0001). CONCLUSION: This study demonstrated while all three modalities are able to provide good information, the sensitivity may alter as the severity of lymphedema progresses. The HFCDU will provide the best detection for lymphatic vessels throughout all stages of lymphedema. However, as each modality provides different and unique information, combining and evaluating the data according to the stage of lymphedema will be able to maximize the chance for a successful surgical outcome.

The Use of Ultrasound Imaging for Upper Extremity Lymphedema after Breast Cancer: A Systematic Review.

BACKGROUND: The aim of this study was to analyze the different applications of ultrasound (US) in upper extremity lymphedema (UEL) after breast cancer. METHODS: A systematic review of the literature was performed in line with the PRISMA statement using MEDLINE/PubMed databases from January 1970 to December 2021. Articles describing the application of US in patients with UEL after breast cancer were included. The quality of the study, the level of reproducibility, and the different applications and type of US technique were analyzed. RESULTS: In total, 30 articles with 1,193 patients were included in the final review. Five different applications were found: (1) diagnosis of UEL (14 studies found a direct correlation between lymphedema and morphological and/or functional parameters); (2) staging/severity of UEL (9 studies found a direct correlation between the clinical stage and the soft-tissue stiffness/texture/thickness); (3) therapeutic assessment (3 studies found an improvement in the circulatory status or in the muscle/subcutaneous thickness after conservative treatments); (4) prognosis assessment of UEL (1 study found a correlation between the venous flow and the risk of UEL); and (5) surgical planning (3 studies determined the location of the lymphatic vessel for lymphovenous anastomosis [LVA] surgery). CONCLUSION: Morphological and functional parameters have been correlated with the diagnosis, stage, therapeutic effect, prognosis of UEL, and surgical planning of LVA.

Clinical Significance Of Dermal Backflow On Lymphoscintigraphy In Patients With Lower Limb Edema.

Chronic blockage of the lymphatic system due to functional or anatomical causes results in lymphoedema which results in swelling due to accumulation of lymphatic fluid in the soft tissue. Lymphoedema commonly affects the upper and lower limbs but may be seen in the neck, chest wall, abdomen and genitalia. Lymphoscintigraphy is non-invasive and maps the lymphatic channels thereby indicating location of blockage along the lymphatic pathways. Blockage of lymphatic channels may lead to back pressure resulting in dermal backflow. We present a case of dermal backflow in bilateral lymphoedema.

Edematous Dermal Thickening on Magnetic Resonance Imaging as a Biomarker for Lymphatic Surgical Outcomes.

Background and Objectives: One of the surgical treatments for breast cancer-related lymphedema (BCRL) is debulking lipectomy. The aim of this study is to investigate whether dermal thickness could be utilized as an objective indicator of post-operative changes following debulking. Materials and Methods: A retrospective review of BCRL patients who underwent debulking lipectomy was conducted. MRI-based dermal thickness was measured by two separate trained readers at 16 regions of the upper extremity. Pre- and post-operative reduction in dermal thickness was compared across the affected and unaffected (control) arms for each patient. The Wilcoxon rank sum test was used to assess for significant change. Univariate linear regression was used to assess the relationship between dermal thickness reduction and changes to LYMPH-Q scores, L-Dex scores, and relative volume change. Results: Seventeen patients were included in our analysis. There was significant reduction in dermal thickness at 5/16 regions in the affected arm. Dermal thickness change was significantly correlated with LYMPH-Q scores, L-Dex scores, and relative volume change in 2/16 limb compartments. There was predominant dermal thickening in the dorsal compartment of the upper arm and in the ventral and ulnar compartments of the forearm. Conclusions: Dermal thickness shows promising utility in tracking post-operative debulking procedures for breast cancer-related lymphedema. Further studies with larger patient populations and a variety of imaging modalities are required to continue to develop a clinically objective and reproducible method of post-surgical lymphedema staging and monitoring.

Utilization of Noncontrast Magnetic Resonance Lymphangiography for Selection of Effective Surgical Method in Breast Cancer-Related Lymphedema.

Background and Objectives: When considering surgery for patients with breast cancer-related lymphedema (BCRL), it is crucial to determine which surgery will be most effective for the patient and establish the indications for each surgery. Our study retrospectively compared the results of preoperative noncontrast MR lymphangiography (NMRL) performed on the lymphedematous limb of patients before surgery, with the aim of analyzing whether preoperative NMRL can be used as a criterion for determining the type of surgery. Materials and Methods: From January 2020 to June 2022, a total of 138 patients with lymphedema underwent surgery at Seoul National University Bundang Hospital. All patients underwent preoperative NMRL imaging and were classified into stages 1-3 based on the MRI severity index using the authors' previous reference. Three types of surgery, LVA, LVA + liposuction, and LVA + VLNT, were conducted on all patients. The effectiveness of the surgery was evaluated one year postoperatively using the interlimb volume difference before and after surgery, the fluid volume of the edematous limb measured by bioimpedance spectroscopy, and the subjective satisfaction of the patients through the Lymph Q questionnaire. Results: In this study, out of a total of 138 patients, 26 (19%) were MRI stage 1, 62 (45%) were stage 2, and 50 (36%) were stage 3. Of the 83 patients who underwent LVA surgery, the greatest decrease in interlimb volume difference was observed in stage 2 patients, and subjective satisfaction was also the most effective in stage 2. In the case of LVA + liposuction patients, a significant volume decrease and a high satisfaction were observed in stage 3 patients. In the case of LVA + VLNT patients, there was no difference in volume decrease according to the stage, but a greater decrease in body fluid volume was observed as the MRI severity index score increased through BIA. Conclusions: In conclusion, this study demonstrates that NMRL imaging is a useful modality for determining the most effective surgical method and predicting the surgical outcome in patients with lymphedema. This highlights the importance of using NMRL in the treatment planning of lymphedema patients.