# Efficacy of Iopamidol for Sealing an Injured Thoracic Duct: Pilot Experiments in a Large Animal
## 4 Discussion  
Post-operative chylothorax occurs in 0.5-2.0% of patients. Although most patients have been conservatively managed, treatments are often ineffective in patients with high flow leaks, requiring prolonged treatment [1; 2; 3; 10]. Recent technological advances have enabled radiological interventions, which have shown relatively good clinical outcomes [5; 6; 9; 11; 13; 14; 19; 20; 21; 22]. However, thoracic embolization or coilization may fail to occlude the thoracic duct in 30% of patients with post-operative chylothorax because of anatomical variations [6; 13; 20; 23]. Despite the frequent failure of this procedure, chylous leakage has been shown to decrease immediately after lymphangiography, which by itself might have an important role in stopping chylous leakage [5; 13; 14; 20; 24; 25]. This could be influenced by lipiodol, which is highly viscous and used as a therapeutic embolic agent. Owing to its characteristics, lipiodol is recommended for use with additional coils in an advanced or gelatin sponge to prevent non-target systemic embolization, such as in the brain and liver [26; 27]. In addition, lipiodol should not be injected at doses exceeding the recommended limit, because it has the potential to cause systemic embolization. We identified ipamidol, which can effectively seal the injured thoracic duct, as an alternative agent that avoids the adverse effects of lipiodol. Iopamidol is an iodinated, water-soluble, highly  
Figure 4: Pathological findings of a damaged thoracic duct. * Amorphous proteinaceous material (iopamidol) in the damaged thoracic duct. Amorphous proteinaceous material is stained red with hematoxylin and eosin stain, but it looks like a liquid rather than a cell. The thoracic duct is a long cylindrical tube; the image shows the collected cylindrical thoracic duct cut along the vertical plane and observed under a microscope. (**A**) represents the cylindrical shape of a thoracic duct and (**B**) represents the shape of a thoracic duct cut along the vertical plane. (**C**) The micrograph shows the left and right parts of a thoracic duct cut along the vertical plane. (hematoxylin and eosin stain, \(\times\) 12.5) (Group A #2 pig). viscous contrast agent that was able to conglomerate with chyle when dropped onto the slide (Figure 4). Furthermore, because of its water solubility [18], isopamidol would rarely cause embolization. The pharmacokinetics of isopamidol showed that the effects of isopamidol were the highest at 30-90 s after injection and that it was eliminated from the plasma in 4 days through the kidney, indicating that isopamidol does not persist longer than lipiodol [18; 28]. Although a few studies have reported the use of lipiodol as a therapeutic embolic agent for lymphangiography [5; 13; 14; 15; 19], other agents, including contrast media such as isopamidol, have not been studied as potential options for this procedure. Our study showed that pin-point tears in the thoracic ducts injured by electrocautery during the operation were healed, and lymphangiography demonstrated prompt sealing of the leak at 10-30 min after the injection of isopamidol. As lipiodol can not only remain in the lymphatic system for a long time but also have a strong ability to embolize [29], the injury of the thoracic duct in all of the pigs might have recovered in just 5 min, unlike that in group A using isopamidol. However, owing to the strong ability of lipiodol, there is a risk of pulmonary embolization or cerebral embolization. Further studies using isopamidol are needed for safe thoracic duct embolization. The disappearance of the leak after isopamidol injection may be affected by the size of injury; therefore, more experiments with defects of varying sizes are needed to evaluate the efficacy of isopamidol. To determine the mechanism of healing, the thoracic duct was extracted and sent to a pathologist for examination. The findings showed that the thoracic duct was full of amorphous proteinaceous material.