Lymphatics, Long a Mystery—Primed to Make History

The anatomical complexity of lymphatic vessels has been understood for centuries, but advancements in physiology and therapeutics have been scarce for much of that history. While major medical progress was being made in many other areas, interest in lymphatics was a relative afterthought and the circulation was a mystery. The lymphatic system had always been difficult to image and treat. In his initial description of pedal lymphangiography in 1955, Kinmoth noted that “lymph vessels, or at least normal ones, are much smaller than the arteries or veins … they contain colorless lymph, which makes them difficult to see, and under normal circumstances they may be empty or nearly so, existing as potential spaces.”[1] The necessity to further develop lymphatic therapeutics was spurred by the desire to improve postoperative outcomes following esophagectomy complicated by chylothorax. Patients could be surgically cured of their cancer, but would then succumb to respiratory compromise, nutritional deficiency, and infections.

Constantine Cope, a pioneering interventional radiologist, launched lymphatic intervention over a series of successive publications in the 1990s.[2] Using the “Kinmoth method” for pedal lymphangiography, Cope could consistently opacify the cisterna chyli.[1] He then demonstrated the feasibility of percutaneously accessing the cisterna chyli and embolizing the thoracic duct, creating a paradigm shift in what was possible. His work culminated in a successful prospective trial of thoracic duct embolization (TDE) for the management of chylothorax, thus becoming a promising therapeutic alternative for patients.[3] [4]

Although there was interest in performing TDE, widespread adoption was initially slow, being limited to a few medical centers. The technical skillset, equipment, and knowledge necessary for pedal lymphangiography were viewed as relics of a former era: the procedure was tedious and could easily occupy an angiography suite for an entire day. Building on Cope's legacy, Max Itkin continued to perform this vital and challenging procedure in high volume, ultimately publishing the largest series of TDE for traumatic chylothorax. Aside from providing compelling evidence for TDE, he further popularized the procedure, becoming both the leading champion and a passionate resource for lymphatic intervention expertise.[5]

The relatively recent advent of intranodal lymphangiography would provide the next major inflection point in the modern history of lymphatic intervention.[6] [7] Compared with pedal lymphangiography, intranodal lymphangiography decreased procedure times by several hours, could be performed with ease, and was applicable for diagnostic exams and procedures. Subsequently, TDE became more widely accessible as did many other lymphatic procedures. Now, nearly 25 years after Cope's initial description of TDE, it is routinely performed with reproducible results and has gained widespread acceptance for the treatment of chylothorax.[8] [9] [10] [11]

Within the last few years, multiple additional authors have further contributed to the body of lymphatic interventional knowledge. Dynamic contrast-enhanced magnetic resonance lymphangiography has improved the sensitivity of lymphatic leak detection, increased the understanding of lymphatic flow anomalies, and aided in procedural planning for complex lymphatic intervention.[12] [13] Successful treatments of pediatric chylothorax, chylous ascites, protein losing enteropathy, and plastic bronchitis are being increasingly described at different medical centers across the world.[14] [15] [16] [17] [18] [19] These treatments involve novel approaches and utilize techniques that include retrograde transvenous lymphangiography, transcervical lymphangiography, thoracic duct stent-grafting, and balloon occlusion retrograde abdominal lymphangiography, among others.[20] [21] [22] [23]

The relationship of lymphatics with fluid balance, nutritional absorption, immunological function, endocrine organs, and spread of malignancy provides the potential to treat many more conditions. As the interplay of lymphatics with increasingly diverse pathophysiology is better understood, lymphatic interventions will undoubtedly grow. Herein, a comprehensive overview of the current practice and techniques involved in lymphatic intervention is presented to update your practice and foster your imagination.

Disclosures

The author created this manuscript and has no relevant disclosures. There was no grant funding or financial support for this manuscript.

• References

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