Lymphatic Research Articles

Quantitative Assessment of Upper-Limb Volume: Implications for Lymphedema Rehabilitation?

Upper-limb lymphedema is a chronic condition characterized by the accumulation of lymphatic fluid in the arm or hand, resulting in swelling and functional impairment. The accurate and reliable volumetric assessment of limb volume is crucial for the correct management of lymphedema. This narrative review provides an overview of the different methods proposed in the literature for the volumetric assessment of upper-limb lymphedema. In more detail, several methods of volumetric assessment have been proposed in recent years, including water displacement, the centimetric method, perometry, bioimpedance spectroscopy, dual-energy X-ray absorptiometry, magnetic resonance imaging, computed tomography, and three-dimensional laser scanning techniques. On the other hand, each method is characterized by specific strengths and limitations in terms of accuracy, reliability, practicality, and cost-effectiveness. Moreover, factors including operator experience, equipment availability, and patient population characteristics might have several implications in the optimal assessment of upper-limb volume. In this context, a precise volumetric assessment is crucial to improving the rehabilitation framework, patient education, and research outcomes. As a result, the integration of emerging technologies is needed to improve the tailored management of patients with upper-limb lymphedema. In conclusion, volumetric assessment methods provide valuable insights in the management of upper-limb lymphedema, improving patient care, treatment outcomes, and research advancements. Future research should focus on testing these innovative solutions on larger samples of patients to enhance the reproducibility, accuracy, accessibility, and clinical utility of volumetric assessment methods in the complex treatment framework of upper-limb lymphedema.

A case of non-immune hydrops fetalis with cystic hygroma complicated by intrauterine fetal death

Hydrops fetalis refers to the excessive accumulation of fluid in the extracellular compartment of the fetus. Cystic hygroma is a congenital malformation of the cervical lymphatic system responsible for an accumulation of lymphatic fluid commonly in the retrocervical region. Cystic hygromas are most often associated with chromosomal abnormalities. When a cystic hygroma is diagnosed in utero, the fetal survival rate is only 2-6%. When hydrops fetalis is present with cystic hygroma, the mortality rate is close to 100%. We present here the case of a 23-year-old primigravida in whom an ultrasound performed at 17 weeks of amenorrhea revealed a posterior cervical cystic hygroma associated with hydrops fetalis, the evolution of which was marked by intrauterine fetal death two weeks later. Keywords: Hydrops fetalis, Cystic hygroma, Chromosomal abnormalities, Prenatal diagnosis.

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

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). 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 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. 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. 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.

Complex decongestive therapy in lymphedema: report from an Interdisciplinary Center

Lymphedema is a chronic and worsening disease due to an abnormal accumulation of liquids, with a high protein content in the interstitial space. The disease is characterized by an insufficient flow of lymphatic fluid, which manifests as edema, inflammation, and fibrosis, all the way up to the stiffening of the affected tissues. Because it's a chronic and increasing disease, the treatment is highly complex. The literature shows that the treatment must be multidisciplinary and it is necessary to combine multiple techniques, such as manual lymphatic drainage, mechanical lymphatic drainage, elasto-compressive bandages and other complementary techniques up to surgical treatment in the most advanced forms which are not responsive to physical therapy. Furthermore, the disease is characterized by episodes of cellulitis, that may lead to infectious complications because the lymphatic function becomes insufficient. A condition of local immunodeficiency is created due to the crucial role that the lymphatic system covers with immune defenses, therefore creates a fertile ground for infections caused by small skin wounds, insect bites, animal scratches, nail fungus, blood draws. Therefore, particular attention is paid to skin folds and interdigital spaces for which hygiene is necessary using neutral detergents, drying by dabbing, and applying emollient creams for skin hydration. Unfortunately, such practices of prevention and care are often underestimated. We provide education of the patient on self-care, such as the self-bandage and the correct application of the elasto-compressed stoking. For wrapping the bandage, it is advisable to wear a glove or a special sock. The multilayer bandages are used in the first decongestant phase while over time the elastic stocking is the best aid for the management of lymphedema. Our clinic is a referral center for diagnosis, treatment and surgical therapy, where patients come for surgical evaluation. Since 2016 we have systematically collected clinical data and volume evaluation of more than 600 cases affected by lymphedema and lipoedema of all stages. They have been treated with complex decongestive therapy for 4 hours a day, 15 consecutive days, subsequently a maintenance of once a week for 3 months, then once a month for 6 months. Of more than 600 patients treated, only 150 were submitted to surgery (lymphatic venous anastomosis, fasciotomy or liposuction, chylothorax and chyloperitoneal shunt, reconstructive plastic of external genitalia). Complex decongestive interdisciplinary therapy, when properly performed can stabilize the lymphedema patient situation, reducing the stage and ensuring a good quality of life.

The vascular system and associated disorders.

The vascular system, also called the circulatory system, is made up of the vessels that carry blood and lymph fluid through the body. The arteries and veins carry blood all over the body, sending oxygen and nutrients to the body tissues and taking away waste materials. This is a complex system in the body and can be affected by diseases with different pathogenic mechanisms. This article describes the pathophysiology of the main diseases of arteries and the venous system.

Evaluation of Interstitium by Lymphatic Uptake Method in Chronic Bilateral Lower Extremity Edema.

Symmetrical bilateral lower extremity edema (BLEE) needs to be treated effectively. Finding the cause of this condition increases the success of treatment. Fluid increase in the interstitial space (FIIS) is always present as a cause or a result. Subcutaneously administered nanocolloid is transported by uptake by lymphatic pre-collectors, and this uptake takes place in the interstitium. We aimed to evaluate the interstitium with labeled nanocolloid and contribute to the differential diagnosis in cases with BLEE. Our retrospective study included 74 female patients who underwent lymphoscintigraphy for bilateral lower extremity edema. Technetium 99m (Tc-99m) albumin colloid (nanocolloid), a marked colloidal suspension, was applied subcutaneously to two different areas on the dorsum of both feet with a 26 gauge needle The dose volume administered intradermally is approximately 0.2-0.3 ml, and each injector has 22-25MBq of activity. Siemens E-Cam dual-headed SPECT gamma camera was used for imaging. Dynamic and scanning images were taken with a high-resolution parallel hole collimator. Ankle images were re-evaluated by two nuclear medicine specialists, independent of physical examination and scintigraphy findings. 74 female patients with bilateral lower extremity edema were divided into two groups based on physical examination and lymphoscintigraphy findings. There were 40 and 34 patients in Groups I and II, respectively. In the physical examination, patients in Group I were evaluated as lymphedema, and patients in Group II were evaluated as lipedema. The main lymphatic channel (MLC) was not observed in any of the patients in Group I in the early images, and the MLC was observed at a low level in the late imaging in 12 patients. The sensitivity of the presence of distal collateral flows (DCF) in the presence of significant MLC in early imaging in demonstrating increased fluid in the interstitial space (FIIS) was calculated as 80%, specificity as 80%, PPV 80%, and NPV 84%. While MLC is present in early images, concomitant DCF occurs in cases of lipoedema. The transport of increased lymph fluid production in this group of patients can be covered by the existing MLC. Although MLC is evident, the presence of significant DCF supports the presence of lipedema. It can be used as an important parameter in the diagnosis in early cases where physical examination findings are not evident.

Effective application of indocyanine green for visualization of the thoracic duct during video-assisted thoracoscopic surgery for chylothorax: a case report

BackgroundChylothorax is an accumulation of typically milky-appearing lymphatic fluid within the pleural cavity. High-output chylothorax may lead to a severe risk of death if not treated promptly. Several studies have reported the effectiveness of indocyanine green (ICG) for chylothorax following lung cancer surgery, esophagectomy, and congenital and recurrent idiopathic chylothorax. Here, we report a case of a successful treatment of idiopathic chylothorax in an adult by identifying and ligating the thoracic duct (TD) using fluorescent thoracoscopy with inguinal lymph node injection of ICG.Case presentationA 79-year-old man with nephrotic syndrome presented with a massive right pleural effusion. Based on the pleural effusion examination, the patient was diagnosed with idiopathic chylothorax. He underwent 26 days of conservative treatments, including intercostal chest tube drainage, subcutaneous injection of a somatostatin analog (octreotide), and diet control (low-fat diet, fasting). However, the conservative treatments failed. Therefore, thoracoscopic TD ligation using a combination of ICG and near-infrared (NIR) light was performed. Ultrasound-guided inguinal lymph node injection of ICG was performed before thoracoscopy. Although standard-mode thoracoscopy could not identify leakage points, when observed under NIR light, the TD could be detected using fluorescence contrast. The TD was clipped to the deepest level on the thoracic side. Furthermore, a fluorescence hotspot of ICG on the cranial side of the clipped TD, likely a leakage point, was confirmed, and the lesion was clipped. ICG fluorescence did not disappear during surgery. The thoracic tube was removed on postoperative day 7. To date, chylothorax has not recurred.ConclusionsWe report the effectiveness of intraoperative NIR fluorescence with ICG in identifying the TD’s running. This technique can lead us to identify and ligate the TD with assurance and accurately treat chylothorax.

Impact of puberty on procedure frequency for treatment of simple head and neck lymphatic and venous malformations

ObjectivePuberty has been shown to accelerate growth of vascular malformations, including lymphatic (LM) and venous malformations (VM). This study aims to compare the number of procedures performed before and after puberty in patients with LM and VM to assess whether the onset of puberty results in higher treatment frequency. MethodsA retrospective review of head and neck LM and VM patients who were evaluated between January 2009 and December 2019 was performed. Patient demographics, lesion characteristics, and procedural details were recorded. For the purposes of this study, 11 years or older in females and 12 years or older in males were the established cut-offs for the onset of puberty. ResultsAfter initial screening of 357 patients, 83 patients were included in the study based on inclusion criteria. There were 34 patients with LM (41 %) and 49 with VM (59 %). The mean age at diagnosis was 6.1 ± 10.9 years (LM: 4.2 ± 7.0, VM: 7.4 ± 12.9, p = 0.489). 68 patients underwent treatments, which included sclerotherapy, surgical excision, and/or laser. For all patients, the average number of lifetime treatments when initiated before puberty was 3.78 ± 2.81 and when initiated after puberty was 2.17 ± 1.37 (p = 0.022). Patients diagnosed pre-puberty were more likely to undergo treatments vs. those diagnosed after puberty (OR 10.00, 95 % CI: 2.61–38.28, p < 0.001). ConclusionWe found that the number of treatments was fewer in those who started treatment after puberty. This finding suggests that providers may elect to proceed with observation in asymptomatic patients, given that waiting until after the onset of puberty has not shown an increase in the procedural load on patients.

Exploring the potential role of health resort medicine in the management of breast cancer-related lymphedema: a viable alternative for innovative rehabilitation opportunities?

Lymphedema is a chronic and progressive disorder of the lymphatic system that impairs the return of lymphatic fluid. Breast cancer treatment can cause breast cancer-related lymphedema (BCRL), with axillary lymph node dissection and regional lymph node radiation being established risk factors. BCRL can cause severe morbidity, disability, and reduced quality of life. Early detection and treatment are essential to prevent the disease from progressing and causing complications. According to the International Society of Lymphology, complex decongestive therapy (CDT) is the most effective conservative treatment for lymphedema. Aquatic exercise is a safe and effective form of therapeutic CDT exercise that can improve joint range of motion, reduce pain, and positively impact limb volume. Additionally, health resort medicine and thermal mineral-rich waters may provide synergistic benefits for therapeutic exercise programs. Therefore, we believe that consideration should be given to whether the spa setting could represent a viable alternative for the rehabilitation of BCRL patients.

A2AR-mediated lymphangiogenesis via VEGFR2 signaling prevents salt-sensitive hypertension.

Excess dietary sodium intake and retention lead to hypertension. Impaired dermal lymphangiogenesis and lymphatic dysfunction-mediated sodium and fluid imbalance are pathological mechanisms. The adenosine A2A receptor (A2AR) is expressed in lymphatic endothelial cells (LECs), while the roles and mechanisms of LEC-A2AR in skin lymphangiogenesis during salt-induced hypertension are not clear. The expression of LEC-A2AR correlated with lymphatic vessel density in both high-salt diet (HSD)-induced hypertensive mice and hypertensive patients. Lymphatic endothelial cell-specific A2AR knockout mice fed HSD exhibited 17 ± 2% increase in blood pressure and 17 ± 3% increase in Na+ content associated with decreased lymphatic density (-19 ± 2%) compared with HSD-WT mice. A2AR activation by agonist CGS21680 increased lymphatic capillary density and decreased blood pressure in HSD-WT mice. Furthermore, this A2AR agonist activated MSK1 directly to promote VEGFR2 activation and endocytosis independently of VEGF as assessed by phosphoprotein profiling and immunoprecipitation assays in LECs. VEGFR2 kinase activity inhibitor fruquintinib or VEGFR2 knockout in LECs but not VEGF-neutralizing antibody bevacizumab suppressed A2AR activation-mediated decrease in blood pressure. Immunostaining revealed phosphorylated VEGFR2 and MSK1 expression in the LECs were positively correlated with skin lymphatic vessel density and A2AR level in hypertensive patients. The study highlights a novel A2AR-mediated VEGF-independent activation of VEGFR2 signaling in dermal lymphangiogenesis and sodium balance, which might be a potential therapeutic target in salt-sensitive hypertension.

Evaluation of Kinesio Taping for Edema, Ecchymosis, and Pain After Liposuction: A Prospective Pilot Study.

Liposuction is a safe, simple, and effective method of body contouring. Pain, ecchymosis, and edema are often local complications at the removal site, especially in the first weeks after surgery. Several studies have shown that kinesiology (kinesio) taping improves blood and lymphatic flow, removing congestions of lymphatic fluid and alleviating hemorrhage. However, there are limited data on the effect of kinesio taping in mitigating local complications at fat grafting donor sites. The aim of this pilot study was to evaluate the impact of kinesio taping in reducing postoperative edema, pain, and ecchymosis in the liposuction area. Over a period of 18 months (January 2021-June 2022), 52 patients underwent liposuction of both flanks with subsequent breast fat grafting. Immediately after the surgery, kinesio taping was used on the right abdomen flank in all patients. Degree of edema as well as ecchymosis and pain were quantified at 7, 14, and 21 days after surgery. There were statistically significant differences in the taping area for ecchymosis at 7 days after surgery, edema at 14 and 21 days after surgery, and in pain, rated on a visual analog scale, at 7, 14 and 21 days after surgery. Kinesio taping, as used in this study, is beneficial in the reduction of edema and pain and the resolution of ecchymosis after liposuction.

Management of a giant lymphocele following varicose vein surgery: a case report

BackgroundA lymphocele or lymphocyst is formed when lymphatic fluid accumulates in a space, following disruption of lymphatic channels. Here, we report a case of a giant lymphocele in a middle-aged female, who underwent Trendelenburg operation (saphenofemoral junction ligation) for varicose veins of her right lower limb.Case presentationA 48-year-old Pakistani Punjabi female presented to the plastic surgery outpatient department with a history of painful, progressive swelling of the right groin and medial aspect of the right thigh for 4 months. After investigation, it was diagnosed as a giant lymphocele. A pedicled gracilis muscle flap was used to reconstruct and obliterate the cavity. There was no recurrence of the swelling.ConclusionLymphocele is a common complication after extensive vascular surgeries. In the unfortunate case of its development, prompt intervention must be done to prevent its growth and ensuing complications.

Pneumatic Compression-Assisted Lymphoscintigraphy for Quantitative Evaluation of Breast Cancer-Related Lymphedema.

Acquired lymphedema of upper extremity is a chronic pathologic status that frequently occurs after breast cancer treatment. Reliable and quantitative evaluation of lymphedema is crucial for successful management of patients. Although lymphoscintigraphy is the primary investigation for the confirmation and evaluation of lymphedema, the specific protocol of stress intervention is not well established. This study aims to introduce intermittent pneumatic compression (IPC) as a part of stress lymphoscintigraphy and compare the effectiveness of conventional stress lymphoscintigraphy (CSL) and pneumatic compression-assisted lymphoscintigraphy (PCAL). Our study was designed as a retrospective analysis of 85 breast cancer patients with lymphedema who underwent lymphoscintigraphy utilizing either IPC device or conventional stress maneuver and received complex decongestive therapy. The flow extent of the lymphatic fluid (FE) was evaluated using a 0- to 4-point scale based on lymphoscintigraphic images. The visualization of lymph nodes was also assessed. The clinical outcomes were evaluated by changes in side-to-side circumferential and volume differences of upper extremities and compared between groups. Of 85 patients, 47 underwent CSL, and 38 underwent PCAL. Participants with relatively preserved flow extent of the lymphatic fluid (FE 3) showed a significant difference in percentage reduction of volume (PRV) between CSL and PCAL groups ( P = 0.036). In the other groups, CSL and PCAL demonstrated comparable differences in PRV without statistical significance. Our study suggests that participants in the PCAL group with relatively preserved lymphatic flow extent (FE 3) had better PRV compared with those in the CSL group. The use of IPC devices in lymphoscintigraphy with the novel stress maneuver can help in the quantitative description of lymphedema status and the selection of an appropriate treatment method.

Genomic profiling informs diagnoses and treatment in vascular anomalies.

Vascular anomalies are malformations or tumors of the blood or lymphatic vasculature and can be life-threatening. Although molecularly targeted therapies can be life-saving, identification of the molecular etiology is often impeded by lack of accessibility to affected tissue samples, mosaicism or insufficient sequencing depth. In a cohort of 356 participants with vascular anomalies, including 104 with primary complex lymphatic anomalies (pCLAs), DNA from CD31+ cells isolated from lymphatic fluid or cell-free DNA from lymphatic fluid or plasma underwent ultra-deep sequencing thereby uncovering pathogenic somatic variants down to a variant allele fraction of 0.15%. A molecular diagnosis, including previously undescribed genetic causes, was obtained in 41% of participants with pCLAs and 72% of participants with other vascular malformations, leading to a new medical therapy for 63% (43/69) of participants and resulting in improvement in 63% (35/55) of participants on therapy. Taken together, these data support the development of liquid biopsy-based diagnostic techniques to identify previously undescribed genotype-phenotype associations and guide medical therapy in individuals with vascular anomalies.

Postesophagectomy chylothorax: a review of the risk factors, diagnosis, and management.

Chylothorax is a crucial postoperative complication of esophagectomy. Characterized by the leakage of chyle and lymphatic fluid through the thoracic duct, chylothorax could result in pleural effusion, respiratory distress, shortness of breath, cardiac arrhythmia, electrolyte imbalance, and malnutrition. Postesophagectomy chylothorax is associated with high morbidity and mortality, and its diagnosis and management require prompt and accurate identification of risk factors and treatment strategies. A variety of strategies are available to treat postesophagectomy chylothorax, ranging from conservative management to pharmacological, lymphangiographic, and surgical treatments. This study reviews the physio-anatomical basis, disease presentation, diagnostic methods, risk factors, and management options for postesophageal chylothorax, filling the literature gap, and highlighting the importance of early recognition and timely intervention in improving patient outcomes.

Microanatomical organization of hepatic venous lymphatic system in humans.

Lymphatic fluid drains from the liver via the periportal lymphatic, hepatic venous lymphatic, and superficial lymphatic systems. We performed a postmortem study to clarify the three-dimensional structure and flow dynamics of the human hepatic venous lymphatic system, as it still remains unclear. Livers were excised whole from three human cadavers, injected with India ink, and sliced into 1-cm sections from which veins were harvested. The distribution of lymphatic vessels was observed in 5 μm sections immunostained for lymphatic and vascular markers (podoplanin and CD31, respectively) using light microscopy. Continuity and density of lymphatic vessel distribution were assessed in en-face whole-mount preparations of veins using stereomicroscopy. The structure of the external hepatic vein wall was assessed with scanning electron microscopy (SEM). The lymphatic dynamics study suggested that lymphatic fluid flows through an extravascular pathway around the central and sublobular veins. A lymphatic vessel network originates in the wall of sublobular veins, with a diameter greater than 110 μm, and the peripheral portions of hepatic veins and continues to the inferior vena cava. The density distribution of lymphatic vessels is smallest in the peripheral portion of the hepatic vein (0.03%) and increases to the proximal portion (0.22%, p = 0.012) and the main trunk (1.01%, p < 0.001), correlating positively with increasing hepatic vein diameter (Rs = 0.67, p < 0.001). We revealed the three-dimensional structure of the human hepatic venous lymphatic system. The results could improve the understanding of lymphatic physiology and liver pathology.

Nafcillin-Loaded Photocrosslinkable Nanocomposite Hydrogels for Biomedical Applications.

Skin infections are frequently treated via intravenous or oral administration of antibiotics, which can lead to serious adverse effects and may sometimes contribute to the proliferation of resistant bacterial strains. Skin represents a convenient pathway for delivering therapeutic compounds, ensured by the high number of blood vessels and amount of lymphatic fluids in the cutaneous tissues, which are systematically connected to the rest of the body. This study provides a novel, straightforward method to obtain nafcillin-loaded photocrosslinkable nanocomposite hydrogels and demonstrates their performance as drug carriers and antimicrobial efficacy against Gram-positive bacteria. The novel formulations obtained, based on polyvinylpyrrolidone, tri(ethylene glycol) divinyl ether crosslinker, hydrophilic bentonite nanoclay, and/or two types of photoactive (TiO2 and ZnO) nanofillers, were characterized using various analytical methods (transmission electron microscopy (TEM), scanning electron microscopy-energy-dispersive X-ray analysis (SEM-EDX), mechanical tests (tension, compression, and shear), ultraviolet-visible spectroscopy (UV-Vis), swelling investigations, and via specific microbiological assays ("agar disc diffusion method" and "time-kill test"). The results reveal that the nanocomposite hydrogel possessed high mechanical resistance, good swelling abilities, and good antimicrobial activity, demonstrating a decrease in the bacteria growth between 3log10 and 2log10 after one hour of direct contact with S. aureus.

The effects of postoperative treadmill exercise on rats with secondary lymphedema.

Cancer-related lymphedema (LE) is often caused by radiotherapy and surgery such as lymph node dissection (LND). Previous studies have reported that exercise is beneficial to relieve LE, but the changes in the lymphatic system following exercise are still unclear. This study aimed to examine the changes in lymphatic drainage pathways over the exercise period and beneficial effects of exercise in rats with LE. Twelve rats were randomly allocated into exercise and control groups (EG and CG; n = 6 each). To obtain LE, inguinal and popliteal LND followed by 20 Gy irradiation was performed. Treadmill exercise was 30 minutes/day, 5 days/week over the four-week period. Consecutive indocyanine green (ICG) lymphography images were collected and classified into five patterns: i) linear; ii) splash; iii) stardust; iv) diffuse, and v) none. Ankle thickness was measured weekly. Histopathological evaluation was performed to examine the skin thickness, collagen area fraction (%) and lymphatic vessel density in harvested tissue. ICG lymphography exhibited more linear and splash patterns in the EG at week 3. The difference of swelling between both groups was significantly different at week 4 (p = 0.016). Histopathologic data revealed a thinner epidermis (p = 0.041) and dermis (p = 0.002), lower collagen area fraction (%, p = 0.002), and higher lymph vessel density (p = 0.002) in the EG than the CG. In conclusion, we found that postoperative exercise can facilitate improvement in lymphatic fluid retention in the lymphedema rat model, resulting in improvement of pathological conditions in the lymphatic system.

PO-04-059 THORACIC DUCT LEAK AFTER DEFIBRILLATOR IMPLANTATION

Device implantation is a relatively low-risk procedure, however generator pocket complications can still occur. In this case, the device site was complicated by a thoracic duct chylous extravasation leading to lymphatic drainage into a device pocket. Case Report A 55-year-old male with ischemic congestive heart failure and reduced ejection fraction of 30-35% and left bundle branch block >150 milliseconds presented several months after cardiac resynchronization therapy-defibrillation (CRT-D) implantation with device site swelling. The physical exam was notable for an extremely swollen left arm consistent with lymphedema. This swelling slowly enlarged for the past 6 months after implantation. Concern was for device site complication with a slowly evolving hematoma that caused compressive lymph stasis. Decision was made for device extraction and reimplantation. Pictured below (Figure 1) shows that the device pocket actually was filled with lymphatic fluid. Upon further investigation, the thoracic duct was either damaged or obstructed and likely the culprit. The pocket was then evacuated with subsequent device extraction and reimplantation. No immediate complications were noted. Upon follow-up, the device site was normal, and left arm lymphedema was resolved. This case demonstrates a rare complication of device implantation that does not appear to be reported in our literature search. Typically hematoma, infection, erosion, migration, and Twiddler’s Syndrome are the most common complications in device pockets. The thoracic duct typically runs from the superior aspect of the cisterna chyli which is situated at the L2 vertebrae and runs to the lower cervical spine. Termination in 95% of patients are either the internal jugular vein, subclavian vein, or the angle between them. However, termination is typically posterior without a superficial course. Lymphatic obstruction tends to be late presenting and can be easily confused with venous obstruction leading to delays in care. Management of lymphatic drainage usually is removing the obstructive source, however, a low fat diet has shown benefit. Thoracic duct complications in device implantation are rare but can lead to delayed treatment and repeat procedures. Further investigation into such cases may be warranted.

Improving lymphatic flow in SLE mice induces fibroblastic reticular cell survival via lymphotoxin beta receptor signaling.

Abstract Systemic lupus erythematosus (SLE) patients are photosensitive, where ultraviolet radiation (UVR) exposure can induce skin inflammation and also trigger systemic disease flares. The link between photosensitive skin and systemic autoimmunity is not well understood. Skin communicates with the immune system via lymphatic vessels that carry lymph into the conduit system of lymph nodes (LNs), which is ensheathed by fibroblastic reticular cells (FRCs). FRCs play critical roles in limiting T and B cell responses. Dendritic cells (DCs) interact both with lymphatic fluid and with FRCs and can modulate FRC survival and numbers via a DC-lymphotoxin beta receptor (LTβR)-FRC axis. We have recently shown dysfunctional lymphatic flow in human SLE and SLE mouse models exposed to UVR and that improving lymphatic flow via manual lymphatic drainage (MLD) reduces skin photosensitivity and LN plasmablast responses, while increasing FRC numbers. In this study, we aim to delineate the mechanism by which MLD induces FRC alterations, hypothesizing that it is via the DC-LTβR-FRC axis. Currently, we have found that MLD increases FRC survival of UVR exposed mice. However, treatment with antagonist LTbR-Ig reverses this FRC survival, suggesting that MLD induces FRC survival via LTbR signaling. Ongoing experiments are targeting the importance of DCs and DC-derived LTβ in modulating MLD-induced changes to FRCs. The novelty of this study is in showing that lymphatic flow from the skin can influence stromal cell populations in SLE. These findings will improve our understanding of the relationship between photosensitivity and systemic autoimmunity.