Liver Lymphatic Anatomy and Its Role in Systemic Health and Disease.

Lymphatic anatomy of the abdomen is reviewed with focus on hepatic and mesenteric vessels in normal and pathologic conditions. Anatomy and pathophysiology is highlight using both specialized fluoroscopy and T2 Dynamic Contrast MR lymphangiography (DCMRL). Plastic bronchitis, chylothorax, protein losing enteropathy, and both cirrhosis and ascites due to hepatic lymphatics are highlighted. Presented at the 2023 ISL International Congress of Lymphology, Genoa, Italy in a special symposium on central and regional lymphatic system in health and disease.

Returning the Central Lymphatic System to the Center of Lymphology.

After the introduction of conventional oil contrast lymphography and the founding of the discipline of lymphology, great impetus was given to investigating central lymphatic system and its disorders along with lymphatic involvement and specifically lymphostasis in common diseases of major organs such as the liver (cirrhosis) and heart (heart failure). Gradually interest shifted to more peripheral disorders such as limb lymphedema and its treatment by physical and surgical measures. At the same time, basic lymphology turned to the study of isolate-ed ex vivo and in vitro, including lymphatic endothelial models and more recently, molecular lymphology focusing on lymphatic growth and modulating factors, genes and proteins under-lying primary lymphedema, and more potential biomarkers of lymphatic disease have gained prominence. However, it has been advances in lymphatic imaging, namely lymphoscintigraphy with SPECT-CT high resolution 3-D pictures and magnetic resonance imaging (contrast and non-contrast) of the peripheral and particularly central lymphatic system by more invasive means combined with endovascular interventional techniques to treat complex and life-threatening lymphatic disorders that has returned the central lymphatic system to the center of lymphology, where the journey began.

Imaging and Interventional Management of Lymphatic Disorders.

Lymphatic flow disorders are reviewed, and a classification based on magnetic resonance lymphography findings outlined. Examples of successful interventional management based on this classification are provided. Presented at the 2023 ISL International Congress of Lymphology, Genoa, Italy in a special symposium on central and regional lymphatic system in health and disease.

The"Overlapping"Lymphaticovenous Anastomosis: an overlapped end-to-end anastomosis supermicrosurgical technique.

OBJECTIVE: Lymphaticovenular anastomosis (LVA) is increasingly utilized in the treatment of lymphedema. This study aims to assess the efficacy and safety of the "Overlapping" LVA technique, which addresses the size mismatch between lymphatic and venous vessels in lymphedema treatment. METHODS: Between August 2022 and April 2023, seventeen patients diagnosed with lymphedema were enrolled in this study. The severity of lymphedema in these patients was classified according to the International Society of Lymphology (ISL) staging system.All patient underwent LVA procedures, anastomosis techniques including the Overlapping, end-to-end and octopus anastomosis. The techniques of anastomosis, anastomosis time, patency rate, and volume of limb lymphedema were evaluated. RESULTS: Our study enrolled 17 lymphedema patients who underwent the LVA procedure. All patients showed significant postoperative improvement in limb edema. The mean drainage volume was 472.29 ml. The Overlapping technique demonstrated a 100% success rate as assessed by clinical observation and intraoperative Indocyanine Green (ICG) lymphography. The average anastomosis time was 5.3 min, reducing operative time compared to traditional methods. CONCLUSIONS: These findings suggest that the Overlapping technique could serve as a valuable addition to the current LVA technique. This Overlapping anastomosis technique provides a wide range of applications for lymphatic anastomosis treatment and prevention of lymphedema.

Single-Center Experience With Dynamic Contrast-Enhanced Magnetic Resonance Lymphangiography for Diagnosing Lymphatic Disorders and Guiding Percutaneous Embolization.

BACKGROUND: The pragmatic role of dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) needs to be evaluated and compared across distinct lymphatic disorders. We aimed to evaluate the performance of DCMRL for identifying the underlying causes of lymphatic disorders and to define the potential benefit of DCMRL for planning lymphatic interventions. METHODS: Patients who underwent DCMRL between August 2017 and July 2022 were included in this retrospective analysis. DCMRL was performed with intranodal injection of a gadolinium-based contrast medium through inguinal lymph nodes under local anesthesia. Technical success of DCMRL and feasibility of percutaneous embolization were assessed based on the lymphatic anatomy visualized by DCMRL. Based on the underlying causes, clinical outcomes were evaluated and compared. RESULTS: Seventy consecutive patients were included. The indications were traumatic chylothorax (n = 42), traumatic chylous ascites (n = 11), and nontraumatic lymphatic leak (n = 17). The technical success rate of DCMRL was the highest in association with nontraumatic lymphatic disorders (94.1% [16/17]), followed by traumatic chylothorax (92.9% [39/42]) and traumatic chylous ascites (81.8% [9/11]). Thirty-one (47.7%) patients among 65 patients who underwent technically successful DCMRL had feasible anatomy for intervention. Clinical success was achieved in 90.3% (28/31) of patients with feasible anatomy for radiologic intervention, while 62.5% (10/16) of patients with anatomical challenges showed improvement. Most patients with traumatic chylothorax showed improvement (92.9% [39/42]), whereas only 23.5% (4/17) of patients with nontraumatic lymphatic disorders showed clinical improvement. CONCLUSION: DCMRL can help identify the underlying causes of lymphatic disorders. The performance of DCMRL and clinical outcomes vary based on the underlying cause. The feasibility of lymphatic intervention can be determined using DCMRL, which can help in predicting clinical outcomes.

[Diagnostic value of fluorescence lymphography for sentinel lymph node biopsy in breast cancer. Summary experience of several specialized centers]. / Diagnosticheskaya tsennost' flyuorestsentnoi limfografii dlya biopsii signal'nykh limfaticheskikh uzlov pri rake molochnoi zhelezy. Obobshchayushchii opyt neskol'kikh spetsializirovannykh tsentrov.

OBJECTIVE: To study the diagnostic value of fluorescent lymphography for sentinel lymph node biopsy in breast cancer. MATERIAL AND METHODS: The cohort study, conducted at 4 specilized centers between June 2019 and March 2024, included 333 patients with cT1-4 N0-1M0 breast cancer. 50 patients received neoadjuvant systemic therapy, 14 of them had single metastases, confirmed by cytological or histological methods, which clinically completely regressed after systemic treatment. Immediately before the operation, 1 ml (5mg) of indocyanine green was injected subareolarly or subcutaneously into the tumor projection. Fluorescence imaging was performed using various devices for ICG navigation in the open surgical field - MARS, IC-Flow, Stryker SPY-PHI, IC-GOR. In 78 patients after sentinel lymph node biopsy standard axillary lymphadenectomy was performed. RESULTS: Detection level was 99.1%. The average number of sentinel lymph nodes was 3.4. Metastatic lesions of sentinel lymph nodes were detected in 54 of 330 patients (16.4%). The average number of metastatic lymph nodes was 1.6; in 90.7% of cases metastases to 1-2 lymph nodes were registered. Intraoperative morphological examination revealed metastases only in 59% of cases. No systemic adverse events were recorded. The false-negative error rate in the group of patients who underwent axillary lymphadenectomy was 6.6%. The overall accuracy of fluorescent lymphography for sentinel lymph node biopsy in breast cancer was 94%. CONCLUSION: The SLNB technique using fluorescence lymphography is safe and highly accurate as a stand-alone method.

Relation Between Characteristics of Indocyanine Green Lymphography and Development of Breast Cancer-Related 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.

Morel-Lavallee associated lymphedema treated with lymphovenous anastomosis: A case report.

Morel-Lavallee Lesions lead to disruption of lymphatic anatomy that require early identification and may necessitate lymphatic reconstruction. We present the case of a 59-year-old male with lower extremity lymphedema resulting after a severe Morel-Lavallee lesion and treated using lymphovenous anastomoses. He was initially managed with multiple aspirations followed by repeat incision and drainage. At 10 months following his injury, he continued to have swelling of his upper thigh and developed a large festoon medially, with lower leg pitting edema. He was diagnosed with lymphedema via lymphoscintigraphy. His superficial lymphatic anatomy was visualized using indocyanine green (ICG) lymphography and showed diffuse dermal backflow across his thigh, with signs of altered lymphatic anatomy distally. We preformed two lymphovenous anastomoses at the level of his mid-thigh to bypass the lymphatic disruption and restore drainage to his lower leg. After rerouting lymphatic flow from the lower extremity, the patient had overall improvement of his symptoms and reduced swelling with continued therapy. At 5 months postoperatively, his volumetric lower extremity measurements showed a decrease by 314 mL and he began walking again in 20-minute intervals. Lymphedema may be an important consideration following severe Morel-Lavallee lesions. Using modern diagnostic and supermicrosurgical techniques, plastic surgeons can help treat this long-term morbidity.

Diagnostic value of combined CT lymphangiography and 99Tcm-DX lymphoscintigraphy in primary chylopericardium.

OBJECTIVE: To investigate the diagnostic value of combined 99Tcm-DX lymphoscintigraphy and CT lymphangiography (CTL) in primary chylopericardium. METHODS: Fifty-five patients diagnosed with primary chylopericardium clinically were retrospectively analyzed. 99Tcm-DX lymphoscintigraphy and CTL were performed in all patients. Primary chylopericardium was classified into three types, according to the 99Tcm-DX lymphoscintigraphy results. The evaluation indexes of CTL include: (1) abnormal contrast distribution in the neck, (2) abnormal contrast distribution in the chest, (3) dilated thoracic duct was defined as when the widest diameter of thoracic duct was > 3 mm, (4) abnormal contrast distribution in abdominal. CTL characteristics were analyzed between different groups, and P < 0.05 was considered a statistically significant difference. RESULTS: Primary chylopericardium showed 12 patients with type I, 14 patients with type II, and 22 patients with type III. The incidence of abnormal contrast distribution in the posterior mediastinum was greater in type I than type III (P = 0.003). The incidence of abnormal contrast distribution in the pericardial and aortopulmonary windows, type I was greater than type III (P = 0.008). And the incidence of abnormal distribution of contrast agent in the bilateral cervical or subclavian region was greater in type II than type III (P = 0.002). CONCLUSION: The combined application of the 99Tcm-DX lymphoscintigraphy and CTL is of great value for the localized and qualitative diagnosis of primary chylopericardium and explore the pathogenesis of lesions.

Morphofunctional Characteristics of the Vessels of the Subareolar Lymphatic Plexus in Breast Cancer with Metastasis to the Lymph Nodes of the Axillary Lymphatic Collector.

The subareolar Sappey's plexus was studied using color lymphography and immunohistochemical methods with a panel of antibodies to podoplanin, smooth muscle actin, low molecular weight cytokeratin AE1/AE3, and GATA3 on archival material obtained during radical mastectomies and sectoral resections with lymph node dissection from 86 patients diagnosed with non-special type breast cancer. At the macro- and microscopic levels, the connection between the subareolar lymphatic plexus and the lymphatic system of the breast parenchyma has been demonstrated. In triple negative breast cancer with metastases to the axillary lymph nodes, the involvement of subareolar lymphatic plexus into lymphogenous metastasis to the lymph nodes of the axillary lymphatic collector was shown.

Usefulness of indocyanine green in the laparoscopic Palomo technique: a comparative study. / Utilidad del verde de indocianina en el procedimiento de Palomo laparoscópico: estudio comparativo.

OBJECTIVE: To find out whether the use of indocyanine green for lymphatic sparing in the laparoscopic Palomo technique reduces the incidence of postoperative hydrocele. MATERIALS AND METHODS: A comparative cohort study of varicocele patients treated with the laparoscopic Palomo technique from 2008 to 2023 was carried out. Patients were divided into two groups according to whether fluorescence lymphography (intratesticular indocyanine green) had been performed or not. Epidemiological, surgical, and clinical data, as well as complications, were recorded. A hypothesis test was conducted using the SPSS software. RESULTS: 30 patients undergoing varicocele surgery through the laparoscopic Palomo technique were included. They were divided into two groups -lymphatic sparing (n= 13) vs. spermatic vessel ligation without sparing (n= 17). Mean age at surgery was 14 years. 5 cases of postoperative hydrocele were identified in the no lymphatic sparing group. 1 of them required surgery for hydrocele treatment. No hydrocele cases were noted in the lymphography group. The difference was statistically significant (p= 0.032). There were no statistically significant differences in terms of operating times or mean hospital stay. No recurrences, postoperative testicular atrophies, or indocyanine-green-related complications were recorded. Mean follow-up was 11.4 months. CONCLUSIONS: The use of indocyanine green for lymphatic sparing in the treatment of varicocele through the laparoscopic Palomo technique significantly reduces the incidence of postoperative hydrocele.

OBJETIVOS: Comprobar si el uso del verde de indocianina para la preservación linfática en la técnica de Palomo laparoscópico reduce la incidencia de hidrocele postoperatorio. MATERIAL Y METODOS: Se realizó un estudio comparativo de cohortes históricas incluyendo los pacientes tratados de varicocele mediante Palomo laparoscópico entre 2008 y 2023. Se dividieron en 2 grupos en función de la realización de linfografía con fluorescencia (verde de indocianina intratesticular). Se recogieron datos epidemiológicos, quirúrgicos, clínicos y complicaciones. Se realizó un análisis de contraste de hipótesis utilizando el programa SPSS. RESULTADOS: Se incluyeron 30 pacientes intervenidos de varicocele mediante la técnica de Palomo laparoscópico divididos en 2 grupos: en 13 se realizó preservación linfática y en 17 ligadura de vasos espermáticos sin preservación. La edad media en el momento de la cirugía fue de 14 años. Se identificaron 5 casos de hidrocele postoperatorio en el grupo sin preservación linfática. Uno requirió intervención quirúrgica para el tratamiento del hidrocele. No se identificó ningún caso de hidrocele en el grupo de la linfografía. La diferencia resultó estadísticamente significativa, p= 0,032. No hubo diferencias estadísticamente significativas en el tiempo quirúrgico ni en la estancia media. No se objetivaron recidivas, atrofias testiculares postquirúrgicas ni complicaciones asociadas al uso del verde de indocianina. El tiempo medio de seguimiento fue 11,4 meses. CONCLUSIONES: El uso del verde de indocianina para la preservación linfática en el tratamiento del varicocele mediante Palomo laparoscópico reduce significativamente la incidencia de hidrocele postoperatorio.

The utility of dynamic contrast-enhanced intranodal magnetic resonance lymphangiography (MRL) in the investigation of primary lymphatic anomalies.

AIM: The aim of this study was to describe the technique of DCMRL to identify central lymphatic abnormalities in patients with primary lymphatic anomalies and discuss utility of the findings. MATERIALS AND METHODS: Twenty-eight patients with primary lymphatic abnormalities underwent dynamic magnetic resonance imaging (MRI) following injection of gadolinium directly into inguinal lymph nodes at a tertiary lymphovascular referral center. RESULTS: Technical success was achieved in 23 patients (82.1%). Pathological imaging findings included obstructed, hypoplastic, or absent lymphatic channels with collateralization/rerouting or reflux of flow, lymphangiectasia, lymphatic pseudoaneurysms, and lymph leaks. Protocol modifications for improved imaging are highlighted including technical aspects of lymph node injection, image acquisition and MRI parameters. In two patients, imaging findings warranted embolization of the abnormal lymphatic channels with subsequent symptomatic improvement. CONCLUSION: DCMRL has been shown to be a safe, reproducible technique in patients with primary lymphatic anomalies enabling imaging of the central lymphatic system.

Lymphaticovenous anastomosis of the caudal thoracic duct to the azygous vein: A feline cadaver study.

OBJECTIVE: The aim of this study was to describe a technique for anastomosis of the thoracic duct (TD) to the azygos vein (AV) using a microvascular anastomotic coupler (MAC) device in feline cadavers. Our hypothesis was that a TD-AV lymphaticovenous anastomosis would be feasible in feline cadavers. STUDY DESIGN: Cadaveric study. ANIMALS: Eight domestic shorthair feline cadavers. METHODS: A left paracostal laparotomy and 9th or 10th intercostal thoracotomy was performed. Contrast media was injected into a mesenteric lymph node and lymphography was used to identify the TD and its branches. The TD and AV were isolated, ligated, and divided with the aid of a surgical microscope. The TD and AV were anastomosed end-to-end using a 1.5 or 2.0 mm MAC. Intraoperative patency was assessed by manipulation of chyle and venous blood across the anastomosis. Mesenteric lymphography was repeated to confirm postoperative anastomotic patency. RESULTS: The TD was identified via lymphography in seven of eight cats. The anastomosis was successful and patency was confirmed via intraoperative assessment and postoperative lymphography in all cats. The median (range) duration for the dissection and anastomosis portions of the procedure was 122 (80-150) min. CONCLUSION: End-to-end anastomosis of the TD to the AV using a MAC was feasible in the feline cadaver without major intraoperative technical challenges. CLINICAL SIGNIFICANCE: Anastomosis of the TD and AV may have application as an alternative treatment for idiopathic chylothorax in cats. By directly connecting the abdominal lymphatics to the central venous system, the stimulus for collateral vessel development around the site of TD ligation may be minimized, which may prevent leakage of chyle through the more cranial lymphatics.

Magnetic resonance lymphography findings across different clinical stages of lower limb lymphedema.

OBJECTIVE: To investigate the findings on lower limb lymphedema using magnetic resonance lymphography (MRL). METHODS: MRL was used to record the lymphatic vessel morphology, distribution of lymphatic vessels, dermal backflow (DBF), and morphology of inguinal lymph nodes in 112 patients (175 affected limbs) with lower limb lymphedema at different clinical stages (according to the International Society of Lymphology staging criteria 2020). RESULTS: The lymphatic vessel morphology significantly differed at different clinical stages (X2 =59.306; P = 0.000). ISL stage I is dominated by "scattered beads" and "branch-like" distribution, ISL stage Ⅱ has tree branch or "capillary-like" distribution, and ISL stage Ⅲ primarily has a capillary pattern and contrast agent accumulation in the foot. There were statistically significant differences in the distribution of lymphatic vessels and DBF in different clinical stages. Distribution of the enhanced lymphatic vessels was distal to the knee in ISL stage I, involved areas below the knee joint or the whole limb in ISL stage II, and involved the whole limb in ISL stage III (X2 =44.591; P = 0.000). With the progression of edema, DBF severity increased (X2 =76.416; P = 0.000). CONCLUSION: MRL revealed the morphology and distribution of lymphatic vessels and detected abnormal inguinal lymph nodes in patients at different stages of lymphedema, which can be used as reference information for surgical treatment.

Lymphatic Interventions in Congenital Heart Disease.

Lymphatic disorders in congenital heart disease can be broadly classified into chest compartment, abdominal compartment, or multicompartment disorders. Heavily T2-weighted noninvasive lymphatic imaging (for anatomy) and invasive dynamic contrast magnetic resonance lymphangiography (for flow) have become the main diagnostic modalities of choice to identify the cause of lymphatic disorders. Selective lymphatic duct embolization (SLDE) has largely replaced total thoracic duct embolization as the main lymphatic therapeutic procedure. Recurrence of symptoms needing repeat interventions is more common in patients who underwent SLDE. Novel surgical and transcatheter thoracic duct decompression strategies are promising, but long-term follow-up is critical and eagerly awaited.

Lymphaticovenous anastomosis map established using lymphatic ultrasound and multi-lymphosome indocyanine green lymphography.

BACKGROUND: Although the usefulness of lymphaticovenous anasotmosis (LVA) for lymphedema has been reported, it is difficult to determine where the LVA is to be performed, especially for inexperienced surgeons. This study aimed to establish a map of the LVA site. METHOD: A total of 105 limbs from 64 patients who underwent lower limb LVA were retrospectively reviewed. Multi-lymphosome indocyanine green (ICG) lymphography (in 35 patients) and lymphatic ultrasound (in all patients) were performed preoperatively and the incision site was determined where dilated lymph vessels and appropriate veins were located in close proximity. The LVA location was identified using a post-operative photograph. Additionally, the degree of lymphatic degeneration at the LVA site was recorded based on the normal, ectasis, contraction, and sclerosis type (NECST) classification. RESULT: A total of 206 skin incisions were analyzed. Among them, 161 (75.9%) were medial and 45 (21.2%) were lateral. Among the 85 sites on the calf, 52 (61.2%) were medial and 33 (38.8%) were lateral. Among the 117 sites on the thigh, 106 (90.6%) were medial and 11 (9.4%) were lateral. As the severity of lymphedema progressed, the probability of performing LVA on the lateral calf increased. Among the 202 locations where LVA was performed on the thigh and lower leg, ectasis type was found in 164 sites (81.2%). CONCLUSION: We established an LVA map of the legs based on multi-lymphosome ICG lymphography and lymphatic ultrasound data. Using this LVA map, surgeons can easily predict the location of lymph vessels, thereby improving the success rate of LVA.

Robot-assisted lymphovenous anastomosis surgery for lymphocele in the groin.

We present the first-in-human robot-assisted microsurgery on a lymphocele in the groin involving a man in his late 60s who had been coping with the condition for 12 months. Despite numerous efforts at conservative treatment and surgical intervention, the lymphocele persisted, leading to a referral to our clinic.Diagnostic techniques, including indocyanine green lymphography and ultrasound, identified one lymphatic vessel draining into the lymphocele. The surgical intervention, conducted with the assistance of a robot and facilitated by the Symani Surgical System (Medical Microinstruments, Calci, Italy), involved a lymphovenous anastomosis and excision of the lymphocele. An end-to-end anastomosis was performed between the lymphatic and venous vessels measuring 1 mm in diameter, using an Ethilon 10-0 suture.The surgery was successful, with no postoperative complications and a prompt recovery. The patient was discharged 3 days postoperatively and exhibited complete recovery at the 14-day follow-up. This case marks the first use of robot-assisted microsurgical lymphovenous anastomosis to address a groin lymphocele, highlighting the benefit of advanced robotic technology in complex lymphatic surgeries.

Analysis on efficacy of magnetic resonance lymphangiography using INV-001 in healthy beagle dogs.

We aimed to conduct a proof-of-concept study of INV-001 in visualizing lymphatic vessels and nodes without venous contamination and to determine the optimal dose condition of INV-001 for magnetic resonance lymphangiography (MRL) in healthy beagles. MRL was performed using a 3.0-Tesla (T) whole body clinical magnetic resonance imaging (MRI) scanner. A dose-finding study of INV-001 for MRL in beagles (N = 6) was carried out according to an adaptive optimal dose finding design. For the reproducibility study (N = 6), MRL was conducted at selected INV-001 doses (0.056 and 0.112 mg Fe/kg) with a 15 mM concentration. Additionally, an excretion study (N = 3) of INV-001 was conducted by analyzing T1, T2, and T2* maps of the liver and kidney 48 h post-administration. INV-001 administration at doses of 0.056 and 0.112 mg Fe/kg (concentration: 15 mM) consistently demonstrated the visualization of contrast-enhanced lymphatic vessels and nodes without venous contamination in the beagles. The contrast enhancement effect was highest at 30 min after INV-001 administration, then gradually decreasing. No toxicity-related issues were identified during the study. After 48 h, the T1, T2, and T2* values in the liver and both kidneys were found to be comparable to the pre-administration values, indicating thorough INV-001 excretion. The optimal dosing conditions of INV-001 for MRL for contrast-enhanced visualization of lymphatic vessels and nodes exclusively with no venous contamination in beagles was determined to be 0.056 mg Fe/kg with a 15 mM concentration.