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Managing Lymphatic Flow Disorders: Expanding Care Through Collaboration

September 14, 2020
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Integration of experts from several subspecialties leads to more options for minimally invasive treatments for children and young adults with often debilitating lymphatic flow disorders.

Alteration in the Lymphatic System Leading to Flow Disorders

The lymphatic system plays a critical role in circulating a clear to yellow-colored fluid called lymph, which contains proteins, immune factors and cells throughout the body. It is also responsible for collecting fats and fat-soluble vitamins from the gastrointestinal tract in cloudy-appearing chylous fluid. This fluid is ultimately delivered to the bloodstream for distribution.

Lymphatic disorders in children are rare conditions that arise when this system is disrupted by either a mechanical/traumatic injury, congenital malformation or elevation in central venous pressure that can be seen in some cardiac disease. Alterations in lymphatic flow can lead to congestion or leakage of lymphatic/chylous fluid in areas of the body, which can manifest as chylothorax, chylous ascites, plastic bronchitis or protein-losing enteropathy. Abnormal fluid accumulation or lymphatic leak can result in significant losses in circulating immune factors, electrolytes, clotting factors and nutritional elements.

Historically, these chronic and debilitating conditions have been challenging to diagnose and manage.

A multidisciplinary team, spear-headed by specialists from interventional radiology, interventional cardiology and hematology/oncology, has come together to provide cutting-edge care for this complex patient population.  New advanced imaging techniques, including dynamic contrast-enhanced magnetic resonance lymphangiography (MRL), have led to a better understanding of the lymphatic system and allow mapping of lymphatic flow dynamics in real time, revealing sites of lymphatic obstruction or leak. In collaboration with primary providers, these improved imaging capabilities and new minimally-invasive lymphatic interventional techniques, allow the team to provide state-of-the-art comprehensive medical care for these often complex patients.

Congenital Lymphatic Channel Disorders

Lymphatic channel disorders are attributed to problems related to the formation and development of lymphatic vessels during pregnancy. While most lymphatic malformations are diagnosed by 2 years of age – many times they are diagnosed at birth – some may be identified in adolescence or early adulthood.

“Depending on the extent of involvement, congenital lymphatic channel or flow disorder symptoms can vary in severity with mild symptoms to life-threating issues associated with effusions, bone pain or bleeding,” explains Bhuvana Setty, MD, vascular anomalies specialist in the Division of Hematology, Oncology & Blood and Marrow Transplant at Nationwide Children’s Hospital. “Patients may not have any symptoms until periods of growth spurts, puberty or pregnancy. These symptoms can be varied from visible defects caused by swelling to chronic chylous losses leading to malnutrition or hemorrhagic effusions and complications thereof which can lead to significant morbidity.”

Lymphatic disorders can have variable appearance. They range from fluid filled cysts that appear like soft smooth masses with a bluish hue. These cysts can cause enlargement of the affected body part. Diffuse and generalized malformations can involve multiple anatomic sites with increased risk of effusions, pain and swelling. There have been advances in medical management that include use of sirolimus in a topical form or oral formulation. Zoledronic acid can be used to manage problematic bony lesions. Advances in research have identified actionable genetic changes that have identified newer targeted agents to treat diffuse, enlarged and symptomatic lymphatic disorders.

Lymphatic Disorders in Congenital Heart Disease

Lymphatic flow disorders associated with cardiac disease include traumatic injury to the thoracic duct following cardiac surgery or congestion/hypertension in the lymphatic system secondary to elevated central venous pressure, which can be seen in palliated single ventricle heart disease, pulmonary hypertension and heart failure.

“Lymphatic flow disorders can lead to serious complications including postoperative chylorthorax, which occurs in 6% of patients undergoing surgery for congenital heart disease,” says Brian Boe, MD, interventional cardiologist at Nationwide Children’s. “Patients with post-operative chylothorax may require long-term drainage via chest tubes in addition to medical therapy including low-fat diet and medication infusions.”  

In the setting of Fontan circulation (the final palliative surgical procedure for many patients with single ventricle cardiac disease whereby systemic venous return is routed directly to the pulmonary arteries), the central venous pressure is elevated as it provides direct blood flow to the lungs. The central lymphatics, which empty into the systemic veins at the left internal jugular/subclavian venous angle,  can become congested as a result of the elevated central venous pressure. In some patients, this can lead to reflux of into the airways causing plastic bronchitis where proteinaceous cast formation within the bronchial tree leading to coughing spells and hypoxia. Chylous fluid can also reflux into the intestinal lumen leading to protein-losing enteropathy and resulting in significant protein loss from the gastrointestinal tract.

Direct Lymphatic Imaging and Minimally Invasive Intervention

Historically, treatment options for lymphatic flow disorders included diet modification, medication and/or surgery to ligate the thoracic duct, the major lymphatic channel in the chest. Thanks to advances in medical imaging, surgical ligation is no longer considered the treatment of choice for patients whose symptoms persist despite maximal medical management.

Enhanced MR imaging allows the team to map the lymphatic channels and evaluate lymphatic flow in real-time using MRL. After directly injecting contrast into the lymphatics either via small needles placed into the inguinal lymph nodes or the peri-portal lymphatics in the liver, interventionalists then image the patient over the subsequent 20-30 minutes in the MRI scanner. This allows them to identify any abnormal channels, leaks or sites of obstruction.

“Correlating the MRL findings with the clinical presentation enables us to determine if the patient might benefit from continued medical therapy, require cardiac catheterization or surgical intervention to address underlying cardiac issues, or possibly be a candidate for minimally-invasive lymphatic interventional techniques,” says Anna Lillis, MD, PhD, pediatric interventional radiologist at Nationwide Children’s. 

Available percutaneous interventions include fluoroscopic-guided catheter-directed embolization of the thoracic duct or selective embolization of other smaller leaking lymphatic channels, procedures performed in the interventional suite – without the patient undergoing open surgery.

A Team Approach for Success

Importantly, the team’s successes thus far are rooted in the unique, collaborative atmosphere.

“Managing lymphatic disorders is a team sport,” says Dr. Setty. “Patients in our care also benefit from the expertise of providers in Physical and Occupational Therapy, Pulmonology, Neonatalogy, Psychology, Plastic Surgery, Dermatology, Otolaryngology, Orthopedics, Pediatric Surgery, Clinical Genetics and Clinical Nutrition, among other specialists, who are integral to ensuring patients achieve the best possible outcomes.”

Working together with the primary medical providers allows the team members to bring their different experience and expertise to help devise the best plan for each individual patient. The team is interested in identifying characteristics that make children better candidates for one type of treatment approach compared to another. Further development and growth of the lymphatic disorders program here at Nationwide Children’s aims to allow for continued innovation as the team works to identify new ways to treat even more children with these complex and chronic conditions.