The Application of Contrast-Enhanced Ultrasound Combined with Indocyanine Green Lymphography in the Management of Secondary Upper Limb Lymphedema.

Near-infrared fluorescent lymphography or indocyanine green (ICG) lymphography is becoming popular in the management of lymphedema. ICG lymphography can clearly visualize superficial lymph flows in real time without radiation exposure. ICG lymphography findings change from normal «linear» pattern to abnormal «dermal backflow (DB)» patterns (mild DB, «splash» pattern; moderate DB, «stardust» pattern; severe DB, «diffuse» pattern) with progression of lymphedema. Splash pattern represents reversible change; on the other hand «stardust» and «diffuse» patterns represent irreversible change. ICG lymphography-based DB stages [arm DB (ADB) stage, leg DB (LDB) stage, genital DB (GDB) stage, and facial DB (FDB) stage] allow pathophysiological severity staging for secondary lymphedema. ICG lymphography also allows classification of primary lymphedema: proximal DB (PDB), distal DB (DDB), less enhancement (LE), and no enhancement (NE) patterns. ICG velocity, representing lymph pump function, decreases with lymphedema progression. ICG lymphography is also used as pre- and intraoperative navigation for lymphatic surgeries such as lymphaticovenular anastomosis, lymph node transfer, and liposuction. In «linear» pattern region, a surgeon can easily find lymphatic vessels. Progression of ICG lymphography pattern represents lymphosclerosis progression. Dynamic ICG lymphography, dual-phase lymphography, allows pathophysiological severity staging, evaluation of lymph pump function, and navigation for lymphatic surgery with only one ICG injection. Dynamic ICG lymphography is useful for the evaluation and treatments of primary and secondary lymphedema.

Background: Breast cancer-related lymphedema (BCRL) is a common complication. Docetaxel (DOC) and paclitaxel (PTX) have been used in taxane-based chemotherapy for breast cancer and to induce fluid retention. The purpose of this study was to investigate the association between lymphatic functionality and the side effects of taxane-based chemotherapy using indocyanine green (ICG) lymphography. Methods and Results: One hundred and eighty breast cancer cases who underwent full-dose taxane-based chemotherapy (DOC or PTX) and complained of upper extremity edema were enrolled in this study. BCRL was diagnosed exclusively on the basis of ICG lymphography results. The characteristics (age, body mass index, laterality, surgery type, regional lymph node irradiation, hormone therapy, and chemotherapy type) of patients diagnosed with BCRL (+) and BCRL (-; fluid retention only) were compared. The side effects were compared in eight categories (neutropenia, skin toxicity, nail changes, myalgia/arthralgia, peripheral neuropathy, stomatitis, dysgeusia, and digestive disease). BCRL (+) consisted of 116 patients and BCRL (-) consisted of 64 patients. BCRL (+) had significantly higher rates of axillary lymph node dissection (98.3%), lymph node irradiation (68.1%), neoadjuvant chemotherapy (14.7%), and DOC (62.9%) than BCRL (-) patients (56.3%, 20.3%, 3.1%, and 34.4%, respectively; p = 0.002 for neoadjuvant rate, p < 0.001 for the other rates). BCRL (+) patients had significantly higher rates of peripheral neuropathy (60.3%) than BCRL (-) patients (40.6%; p = 0.01). Conclusions: The occurrence rate of BCRL increased for the patients with peripheral neuropathy induced by taxane-based chemotherapy. This implies that peripheral neuropathy can induce BCRL.

Indocyanine green (ICG) lymphography is becoming popular in lymphedema management, since it can visualize superficial lymph flows in real time without radiation exposure. With lymphedema progression, ICG lymphography pattern changes from normal linear pattern to abnormal dermal backflow (DB) patterns (splash, stardust, and diffuse patterns). Splash represents mild DB and reversible change; on the other hand, stardust/diffuse represents moderate/severe DB and irreversible change. DB stages [leg DB (LDB) stage, arm DB (ADB) stage, genital DB (GDB) stage, and facial DB (FDB) stage] allow pathophysiological lymphedema severity staging based on ICG lymphography findings. ICG velocity, lymph pump function, decreases as lymphedema progresses. ICG lymphography is also used as pre- and intraoperative navigation for lymphatic supermicrosurgery such as lymphaticovenular anastomosis. A surgeon can easily find lymphatic vessels in linear pattern. Progression of ICG lymphography pattern represents progression of lymphosclerosis; the more severe DB pattern is detected on ICG lymphography, the more sclerotic lymphatic vessels are. Dynamic ICG lymphography, dual-phase lymphography, allows pathophysiological severity staging, evaluation of lymph transportation capacity, and navigation for lymphatic surgery with one ICG injection. Dynamic ICG lymphography is useful for evaluation of lymphedema prognosis and therapeutic interventions.

Background/Objectives: Breast cancer-related lymphedema (BCRL) is one of the major morbidity in breast cancer. Since lymphedema treatment is difficult, especially once it progresses, screening and early detection should be prioritized to prevent the progression. This study used indocyanine green lymphography (ICG-L) as a sensitive diagnostic tool for BCRL screening after axillary lymph node dissection (ALND). Methods: This prospective cohort study included breast cancer patients who underwent ALND from October 2022 to October 2024 at Dharmais National Cancer Hospital. ICG-L was performed to diagnose BCRL. Our study outcome was a 2-year BCRL cumulative incidence and ICG-L stage distribution. Results: This study included 69 patients with a mean body mass index of 26.3±5.1 kg/m2. The median (IQR) of dissected lymph nodes was 18 (14-21), with the number of lymph node metastases 2 (0-10). Forty-six patients (66.7%) were in the locally advanced stage and 42 (60.9%) received radiotherapy. Based on ICG-L, our 2-year BCRL cumulative incidence was 58.0% (45.2-71.4). A total of 25 patients (71.4%) who had BCRL experienced symptoms, with heaviness (60%) and swelling (48%) being the most common signs. The upper extremity lymphedema index increase of &amp;amp;gt; 10 % was only found in 11 (31.4%) patients. Most patients were in ICG-L stage II, as shown in 18 (51.4%) subjects. Conclusions: ICG-L was able to detect early BCRL more frequently. This finding showed its sensitivity as a screening method and that it should be used in preventive BCRL management.

Background: The axillo-inguinal (or inguino-axillary) is a compensatory lymphatic drainage pathway regularly utilized by lymphedema therapists when applying manual lymphatic drainage (MLD) for upper and lower extremity lymphedema. However, there is limited evidence of the frequency of this pathway and the characteristics of patients with lymphedema in which this pathway is present. Indocyanine green (ICG) lymphography is an imaging technique that has the capability to identify lymphatic drainage pathways in lymphedema when combined with MLD. In this study, we used ICG lymphography in patients with upper and lower extremity lymphedema to investigate the presence of this pathway and its clinical characteristics. Methods and Results: A retrospective cohort audit of 563 patients with lymphedema (285 with upper extremity and 278 with lower extremity) who underwent ICG lymphography was conducted in combination with MLD. Compensatory lymphatic drainage was investigated. Patients demonstrating the axillo-inguinal pathway were identified, and their clinical characteristics were recorded. The axillo-inguinal pathway was not demonstrated in any patient with upper extremity and only five patients with lower extremity lymphedema. Of these five patients, all were female with a history of secondary cancer-related lymphedema following gynecological cancer. The majority (four) had bilateral lymphedema extending to the lower abdomen and presented with a greater severity of lymphedema. Conclusions: These findings suggest that the axillo-inguinal pathway is an infrequent compensatory drainage pathway in lower extremity lymphedema and rare in upper extremity lymphedema. Our findings have clinical implications for lymphedema management, in particular, the sequence in which MLD is applied.

Background: Indocyanine green (ICG) lymphography is a newer technique for diagnosing lymphedema. Our study aimed to find whether the abnormality of ICG lymphography can predict the occurrence of early lymphedema and then select candidates at high risk of developing lymphedema. Methods: Postoperative breast cancer patients who visited the lymphedema clinic of Peking University People’s Hospital from December 2016 to September 2019 were consecutively enrolled and received ICG lymphography and circumference measurement. Data were collected on the patients’ characteristics and correlation between ICG lymphography and the occurrence of lymphedema. Results: The analysis included 179 patients. There were 91 patients in the lymphedema group and 88 patients in the non-lymphedema group. By multivariate analysis, age, axillary surgery, radiotherapy, and time since breast cancer surgery were regarded as risk factors for lymphedema (p < 0.05). According to the results of ICG lymphography, patients in the non-lymphedema group (n = 88) were divided into ICG-positive (n = 47) and ICG-negative (n = 41) groups. The incidence of lymphedema in the ICG-positive group was significantly higher than that in the ICG-negative group (19.1% vs. 2.4%, p = 0.027). Conclusion: Lymphatic disorder can be detected before circumference change using ICG lymphography. Abnormal ICG lymphography is an independent risk factor for lymphedema. Patients with abnormal dermal backflow patterns are considered to be a high-risk group for lymphedema and should undergo early interventions to prevent lymphedema.

Background: Breast cancer-related lymphedema (BCRL) is a disabling and frequently occurring condition after treatment for breast cancer. Studying lymph anatomy by means of indocyanine green (ICG) lymphography is a promising tool to help better understand BCRL. The aim of this study is to investigate the relation between ICG lymphography characteristics and the risk of developing BCRL. Methods and Results: Patients scheduled for breast surgery with either unilateral axillary lymph node dissection or sentinel lymph node biopsy between November 2017 and May 2019 were included. Patients were assessed at baseline and up to 36 months postsurgery. BCRL was defined as an increase of ≥5% relative arm volume difference compared with the presurgical difference. In total, 128 patients were included. During 36 months of follow-up, 45 patients (35.2%) developed BCRL. The number of lymph vessels before surgery was not a statistically significant risk factor for developing BCRL (p = 0.8485). However, an increase in the number of lymph vessels compared with baseline was a significant protective factor for developing BCRL (odds ratio = 0.8). An increase of one lymph vessel corresponds to a 19% relative risk reduction of developing BCRL. The presence of lymph nodes at baseline and the change in the presence of lymph nodes compared with baseline were no predictors for the development of BCRL (p = 0.0986 and p = 0.8910, respectively). Conclusions: An increase in the number of lymph vessels visualized by ICG lymphography compared with baseline is a protective factor for developing BCRL. Therapies with the ability to increase the number of lymph vessels can thus possibly decrease the risk of developing BCRL.

Lymphatic ultrasound detects more vessels than indocyanine green lymphography in lymphedematous limbs.

Background: Vascularized lymph node flap transfer is a recent approach used for the treatment of breast cancer-related upper limb lymphedema. Objective: This work aims to evaluate the effect of vascularized lymph node transfer in the management of secondary upper extremity lymphedema. Methods: a prospective randomized clinical study was conducted including 30 patients stage II-III breast cancer-related lymphedema (BCRL) between December 2017 till June 2020. 15 patients underwent vascularized groin lymph node flap transfer (group B) using the axilla (n = 7) or distal placement (elbow/wrist) (n = 8) as a recipient site. 15 patients who were selected to undergo conservative therapy were used as controls. Intraoperatively, reverse lymphatic mapping using radioisotope or indocyanine green lymphography was performed to avoid iatrogenic lower extremity lymphatic injury. Outcomes were assessed using change of circumferential differentiation, volume reduction rate, and the change in episodes of cellulitis, pain, heaviness, and limb function. Results: At a mean follow-up of 30.07±2.6 months, the mean improvement of circumferential differentiation of group B (VGLNT) was statistically greater than that of group A (conservative physical therapy) (8.3 ± 2.7 percent versus 2.1 ± 4.6; P < 0.01). The evaluation of each treatment showed a significant reduction of infection rate in group B compared with group A (p < 0.001). Conclusion: Vascularized groin lymph node flap transfer using the axilla or distal forearm as a recipient site is an effective and reliable approach for treating breast cancer-related lymphedema.

BACKGROUND: Indocyanine green (ICG) lymphography is an advanced imaging tool that can visualize superficial lymph flow and has been a vital part of lymphedema diagnosis, management, and tracking in patients with lymphedema. The goal of this prospective study was to determine the effect of exercise on the time it takes ICG dye to show full lymphedema disease pattern during ICG lymphography, with the intent to create a standardized and accelerated ICG lymphography protocol in patients with lymphedema. METHODS: Nine patients (10 arms, 13 legs) with unilateral and bilateral lymphedema exercised on a recumbent cross trainer for five minute intervals at a rated perceived exertion of 11–13. ICG lymphography scans were performed before exercise, after each 5-minute exercise interval to identify plateau time, and then every hour after the initial scan for 6 hours. A postintervention survey was provided to the patient assessing their opinion of exercise on the process. RESULTS: The ICG dye plateaued after 3 cycles of exercise (15 minutes of exercise in total) in all limbs studied, and the dye was shown to start receding after 4 hours. Patients preferred exercising to speed up ICG studies compared with the traditional method, which involves waiting between 6 and 24 hours between initial and delayed ICG lymphography scans. CONCLUSIONS: Exercise can accelerate lymph flow, with disease pattern plateauing at 15 minutes of exercise in patients with lymphedema. From this we know that exercise allows for more efficient and standardized ICG lymphography studies.

Current predictive models of lymphedema risk cannot predict with 100% certainty which patients will go on to develop lymphedema and which will not. Patient-specific anatomic and physiologic differences may be the missing factor. The authors hypothesize that patients with accessory lymphatic pathways may have improved lymphatic drainage, resulting in smaller limb volumes. The authors reviewed indocyanine green (ICG) lymphography images of all patients who presented to their institution for evaluation of breast cancer-related lymphedema. Patients with unilateral upper extremity lymphedema, a full set of bilateral limb measurements, and ICG images of both limbs were included. Other variables of interest included patient demographics and length of follow-up. Patients with accessory pathways were determined independently, and conflicts were resolved with discussion. Abnormal images were also evaluated for common drainage pathways. Thirty patients were identified as having accessory lymphatic drainage pathways. These patients had significantly smaller limb volume differences [8.19% (SD, 11.22)] compared with patients who did not exhibit these pathways [20.74% (SD, 19.76); P < 0.001]. The most common pathway was absence or rerouting of the radial bundle to the ulnar or volar bundles ( n = 16). The ability to create accessory lymphatic drainage pathways may be associated with improved lymphatic drainage, resulting in smaller limb volumes. Furthermore, certain drainage pathways appear to be more common than others. Description of these pathways should be considered for inclusion in ICG lymphography image grading criteria. Further study is needed to clarify the nature of these pathways and whether these pathways affect subjective symptoms and quality of life. Risk, II.

Primary lymphedema is caused by various lymphatic malformations and has a wide variety of etiology. Lymphatic image is important to understand underlying pathophysiology of primary lymphedema. Indocyanine green (ICG) lymphography allows very clear superficial lymph flow visualization in real time, which can be performed less invasively without radiation exposure. With progression of lymphedema, ICG lymphography finding changes from linear pattern to splash, to stardust, and finally to diffuse pattern. Different ICG lymphography pattern represents different lymphatic vessel conditions; lymphatic vessel becomes more sclerotic with progression of ICG lymphography findings. Primary lymphedema can be classified into four patterns based on ICG lymphography findings; proximal dermal backflow (PDB), distal dermal backflow (DDB), less enhancement (LE), and no enhancement (NE) patterns. In PDB and DDB patterns, lymph flow obstruction is a main cause of lymphedema, and lymphatic bypass operation can be a useful therapeutic option for compression-refractory lymphedema. In LE pattern, non-obstructive mechanism such as lymph pump dysfunction is considered a cause of lymphedema, and strict compression therapy is recommended. In NE pattern, whole limb severe hypoplasia or aplasia is suspected, and vascularized lymph node transfer may be better indicated than lymphatic bypass operation. ICG lymphography is useful not only for lymphedema evaluation but also for navigation of lymphatic surgery.

Concordance between preoperative imaging methods in patients with limb lymphedema undergoing supermicrosurgical lymphaticovenular anastomosis

Preoperative mapping of lymphatic vessels for lymphovenous anastomosis (LVA) surgery is frequently performed by indocyanine green (ICG) lymphography solely; however, other imaging modalities, such as ultrasound (US), might be more efficient, particularly for Caucasian patients. We present our preoperative assessment protocol, experience, and approach of using US for locating optimal LVA sites. Fifty-six (16 males) lymphedema patients who underwent LVA surgery were included in this study, 5 of whom received two LVA operations. In total, 61 LVA procedures with 233 dissected lymphatic vessels were evaluated. Preoperative US was performed by the author S.M. 2 days before intraoperative ICG lymphography. Fluid-predominant lymphedema regions were scanned more profoundly. Skin incisions followed preoperative US and ICG lymphography markings. Detection of lymphatic vessels was compared between ICG lymphography and the US by using the intraoperative verification under the microscope with 20 to 50x magnification as the reference standard. Among the dissected lymphatic vessels, 83.3% could be localized by US, and 70% were detectable exclusively by it. In all, 7.2% of US-detected lymphatic vessels could not be found and verified intraoperatively. Among the lymphatic vessels found by US, only 16% were apparent with ICG before skin incision. In total, 23.2% of the dissected lymphatic vessels could be visualized with ICG lymphography preoperatively. Only 9.9% of the lymphatic vessels could be found by ICG alone. High-frequency US mapping accurately finds functional lymphatic vessels and matching veins. It locates fluid-predominant regions for targeted LVA surgeries. It reveals 3.6 times as many lymphatic vessels as ICG lymphography. In our practice, it has an integral role in planning LVA procedures.

To conduct a randomized controlled trial (RCT) on the efficacy of immediate lymphatic reconstruction (ILR) for decreasing the incidence of breast cancer-related lymphedema (BCRL) after axillary lymph node dissection (ALND). Despite encouraging results in small studies, an appropriately powered RCT on ILR has not been performed. Women undergoing ALND for breast cancer were randomized in the operating room 1:1 to either ILR, if technically feasible, or no ILR (control). The ILR group underwent lymphatic anastomosis to a regional vein using microsurgical techniques; control group had no repair and cut lymphatics were ligated. Relative volume change (RVC), bioimpedance, quality of life (QoL), and compression use were evaluated at baseline and every 6 months postoperatively up to 24 months. Indocyanine green (ICG) lymphography was performed at baseline and 12 and 24 months postoperatively. The primary outcome was the incidence of BCRL, defined as ≥10% RVC from baseline in the affected extremity at 12-, 18-, or 24-month follow-up. Of 72 patients randomized to ILR and 72 to control from January 2020 to March 2023, our preliminary analysis includes 99 patients with 12-month follow-up, 70 with 18-month follow-up, and 40 with 24-month follow-up. The cumulative incidence of BCRL was 9.5% in the ILR group and 32% in the control group ( P =0.014). The ILR group had lower bioimpedance values, decreased compression usage, better lymphatic function on ICG lymphography, and better QoL than the control group. Preliminary results of our RCT show that ILR after ALND decreases BCRL incidence. Our goal is to finish the accrual of 174 patients with 24-month follow-up.