Lymphorrhea is a postoperative complication of gastrointestinal surgery that occur with lymph node dissection and thoracic duct injury. Thoracic duct injury, especially after esophagectomy, can result in massive lymphatic leakage. Lymphorrhea has conventionally been treated either conservatively or surgically. However, conservative management includes fasting and fat restriction, and these continued long-term conservative management can affect postoperative recovery. Lymph contains lymphocytes, albumin, and electrolytes, and the continued loss of more than 1 L of lymph per day causes immunodeficiency and hypoalbuminemia.^1,2 If more than 1 L per day of chylous pleural effusion is being drained, the mortality rate with continued conservative management reportedly exceeds 50% and surgical thoracic duct ligation should be proactively conducted, but this is not an easy procedure.^2–7 Lymphatic interventional radiology has recently been attracting attention as a treatment method for lymphorrhea following gastrointestinal surgery.

Lipiodol (Guerbet, Aulnay-sous-Bois, France) lymphangiography has been conducted to diagnose lymphorrhea. Pedal lymphangiography involves making an incision in the dorsum of the foot and directly puncturing the exposed lymphatic vessel with a needle and has a long history.⁸ Lipiodol is injected via a special pump in pedal lymphangiography that requires time and expertise. However, Lipiodol lymphangiography is essential for identification of the site of lymphorrhea and planning access in order to conduct interventional radiology.⁹ The difficulty of pedal lymphangiography means that for a long time, lymphatic interventional radiology was only conducted in a limited number of institutions. From around 2012, however, procedures using intranodal lymphangiography rather than pedal lymphangiography were reported, enabling interventional radiologists to take on a role in the treatment of lymphorrhea.^10,11 Improvements in ultrasound device performance now enable the clear visualization of superficial lymph nodes and fine-diameter puncture needles, which may be one of the factors in the spread of intranodal lymphangiography. The three-dimensional images provided by interventional radiology, computed tomography (CT), and cone-beam CT, and the improved diagnostic performance for the lymphatic system provided by magnetic resonance (MR) lymphangiography, are also helpful for interventional radiological treatment.^12,13

In this report, we discuss lymphatic interventional radiology for lymphorrhea following gastrointestinal surgery.

If lymphorrhea can be diagnosed by Lipiodol nodal lymphangiography, interventional radiologists can provide information that is useful not only for the treatment of lymphorrhea, but also for surgical treatment. Standard nodal lymphangiography is conducted by puncturing the inguinal or femoral lymph nodes, but if a lymph node can be punctured then anywhere in that region can be enhanced by contrast. Puncturing an axillary, cervical, para-aortic, or mesenteric lymph node enables lymphangiography in these regions.

Lymph node puncture is conducted under ultrasound guidance, using a high-frequency (13-MHz) linear probe. A 23-gauge Cathelin needle (Terumo Europe, Leuven, Belgium) or spinal needle is used for the puncture. Lymph nodes are not difficult to visualize if a high-frequency probe is used. After confirming that the tip of the needle is inside the lymph node on the ultrasound image, Lipiodol is injected (Fig. 1A). The start of Lipiodol injection should be observed by fluoroscopy. If the puncture has been successful, the lymph node is visualized in granular form by the injected Lipiodol, and the lymphatic vessels extending from the node are immediately visualized (Fig. 1B, 1C).¹¹

Figure 1. Intranodal lymphangiography. (A) Ultrasound-guided lymph node puncture. A 23-gauge Cathelin needle (white arrow) and lymph node (white arrowheads) are seen. (B) If puncture is successful, the lymph node is visualized in granular form by the injected Lipiodol (black arrow), and lymphatic vessels extending from the lymph node are immediately visualized. (C) Lipiodol lymphangiography of the pelvis.

To avoid excessive radiation exposure, the injection need not be observed by continuous fluoroscopy, but should be checked intermittently. It is also necessary to check that the needle has not slipped out of the lymph node to cause leakage, and that large amounts of Lipiodol are not leaking into the veins. Lipiodol may enter a vein either through a lymphaticovenous anastomosis, or directly into the vein from the punctured lymph node.¹¹ As the Lipiodol ultimately enters the venous system via the thoracic duct, a small amount of leakage into veins is tolerable, but a large amount of leakage requires puncture of another lymph node. The total amount of Lipiodol injected should be under 14 mL,¹⁴ with this amount reduced further for children and patients with poor respiratory function. The success rate for intranodal lymphangiography is high, at 90%–100%.^15–18

Although lymphangiography is conducted for diagnostic purpose, the amount of leakage could be subsequently decreased; thus, the lymphangiography also has a therapeutic effect on lymphorrhea.^19–22 Two possible mechanism of Lipiodol action have been posited, although neither has yet been confirmed. One is that Lipiodol leaking through the damaged part of the lymphatic vessel induces an inflammatory response that closes off the lymphatic vessel. The second is that Lipiodol acts as an embolizing substance. In a study by Matsumoto et al,²⁰ when conservative treatment was continued after lymphangiography, lymphorrhea stopped in 89% of patients after a mean duration of 17 days (range 4–31 days). According to Alejandre-Lafont et al,²¹ lymphorrhea stopped within 2 weeks of lymphangiography in 51% of patients and within 1 week in 44%, with a ≥ 50% decrease in lymphorrhea in 12% of cases. This indicates that conservative treatment must be continued after therapeutic lymphangiography, and that in some cases the lymphorrhea may only diminish rather than stopping. Because intranodal lymphangiography is an easier procedure than pedal lymphangiography, repeated performance is less burdensome, and the duration of conservative treatment may be reduced.¹¹

In this method, an embolizing substance other than Lipiodol is injected into the lymphatic vessel to stop the flow of lymph. A mixture of n-butyl cyanoacrylate (NBCA) and Lipiodol is usually used as the embolizing substance. This embolic material can be injected into the lymphatic vessel by one of two methods, either puncturing the lymphatic vessel directly with a fine-gauge needle or by puncturing a lymph node. Only a limited number of reports have described direct puncture of lymphatic vessels,²² with most cases involving puncture of a lymph node. The lymph node to be punctured may be para-aortic, iliac, or inguinal.^23–26 Intranodal lymphangiography is first conducted via the groin or femur to identify the site of leakage and the nearest upstream lymph node (Fig. 2A). If a lymph node upstream from the leakage site can be punctured, lymphangiography is conducted from this node to confirm the site of leakage and the course of the lymphatic vessel leading to it (Fig. 2B). If the contrast agent rapidly reaches the leakage site from the punctured lymph node, high-concentration NBCA can be injected, while low-concentration NBCA is used if the contrast is slow to reach the node (Fig. 2C). The ratios of NBCA to Lipiodol reportedly used are between 1 : 1 and 1 : 8.^23–26 Clinical success was achieved in 6 of 7 patients reported by Nadolski et al,²³ 9 of 9 patients reported by Chu et al,²⁴ and 20 of 21 patients reported by Baek et al.²⁵ Kim et al²⁶ reported that the success rate of lymphatic embolization was 83.3%, higher than the 43.8% success rate from sclerotherapy instilling ethanol into the cavity of lymphorrhea.

Figure 2. Lymphatic embolization. (A) Lymphorrhea (white arrowhead) and an upstream lymph node (white arrow) are seen. (B) Upstream lymph node puncture under fluoroscopic observation, showing the injection needle (black arrow). (C) Injection of n-butyl cyanoacrylate. In this case, the ratio of n-butyl cyanoacrylate to Lipiodol was 1 : 2 and 2.4 mL of the mixture was injected.

Thoracic duct embolization is conducted to treat chylous pleural effusion caused by breakdown of the thoracic duct or its branches. A catheter must first be inserted into the thoracic duct. Once the catheter has been placed, the thoracic duct is contrast-enhanced with water-soluble contrast agent to identify the site of leakage. If the leakage site can be identified, transcatheter embolization is conducted. The thoracic duct may be approached via transvenous retrograde thoracic duct cannulation or transabdominal thoracic duct cannulation.

In transvenous retrograde thoracic duct cannulation, Lipiodol lymphangiography is first conducted to identify the junction of the thoracic duct with the vein. An introducer sheath is inserted via the brachial vein and the tip of a 4- or 5-Fr catheter is advanced to the junction of the thoracic duct. After the tip of the catheter has been placed in the thoracic duct, a microcatheter is advanced into the thoracic duct in the retrograde direction until reaching the cisterna chyli. The thoracic duct contains many irregularities and numerous valves, making catheter advancement difficult. The cervical part of the thoracic duct in particular contains branches flowing in from the neck and arms that are not visualized by lymphangiography, as well as numerous valves. The cervical part also exhibits a plexiform morphology in 23%–26% of cases; in such cases, retrograde cannulation is impossible.^15,27,28 If the microcatheter does reach the cisterna chyli, thoracic ductography is conducted with water-soluble iodine contrast agent to identify the site of leakage (Fig. 3). The frequency of the catheter reaching the cisterna chyli in transvenous retrograde thoracic duct cannulation has been reported as 46.2%.²⁷

Figure 3. Transvenous retrograde thoracic duct contrast. The thoracic duct (white arrows) are seen.

In transabdominal thoracic duct cannulation, the cisterna chyli is visualized by lymphangiography from the leg and punctured transabdominally under X-ray fluoroscopy. When the cisterna chyli has been successfully punctured, a microguidewire is inserted and advanced from the cisterna chyli into the thoracic duct (Fig. 4A). A microcatheter is inserted over the wire into the thoracic duct, which is enhanced with a water-soluble iodine contrast agent to identify the site of leakage (Fig. 4B). NBCA is used as the embolizing substance.

Figure 4. Percutaneous transabdominal thoracic duct approach. (A) Percutaneous transabdominal puncture of the cisterna chyli (white arrowheads) by a 22-gauge Chiba needle (white arrow). (B) Percutaneous transabdominal thoracic ductography. Extravasation of contrast agent (black arrows) from the thoracic duct is evident.

Itkin et al¹⁵ investigated 109 cases of thoracic duct embolization conducted between 1996 and 2009 for patients with severe chylous pleural effusion due to damage to the thoracic duct, including iatrogenic damage. They found the catheter was successfully introduced into the thoracic duct in 73 patients (67.0%), transcatheter thoracic duct embolization was conducted in 71, and this embolization was successful in 64 (90.1%). Complications comprised 1 case of symptomatic pulmonary embolism caused by glue, 2 cases of edema of the legs, and 2 cases of infection of the incision in the dorsum of the foot. A meta-analysis by Kim et al²⁹ reported that the pooled technical success rate of thoracic duct embolization was 63.1% and the pooled clinical success rate was 79.4%.

Chronic complications in 78 patients who underwent a mean 34 months of follow-up after thoracic duct embolization comprised swelling of the legs in 4 patients and diarrhea in 4.³⁰

Lymph produced in the liver drains into the cisterna chyli via the hepatic lymphatic vessels, reaching the venous angle via the thoracic duct from the cisterna chyli. Hepatic lymphangiography is effective for lymphorrhea after periceliac lymph node dissection during gastrointestinal surgery.^9,31 The hepatic lymphatic vessels cannot be visualized in lymphangiography from the legs unless there is a retrograde flow of lymph from the cisterna chyli. Hepatic lymphangiography is therefore performed via the percutaneous transhepatic route in the same way as portal vein or bile duct puncture. The space of Disse is located around the portal vein, with lymph flowing through. In percutaneous transhepatic hepatic lymphangiography, contrast is conducted by puncturing the portal vein margin. As a result, rather than via intrahepatic lymphatic vessel puncture, contrast agent can be injected into the space of Disse to flow into the hepatic lymphatic vessels (Fig. 5).³² If leakage is identified in hepatic lymphangiography, hepatic lymphatic vessel embolization is conducted immediately. Because microcatheter insertion is infeasible, hepatic lymphatic vessel embolization is conducted by direct injection of the embolizing substance via the puncture needle. NBCA is used as the embolizing material, but because of the distance from the needle tip to the leakage site, a mixture containing a low proportion of NBCA is used.^31,33

Figure 5. Hepatic lymphangiography. A 22-gauge Chiba needle (white arrow) and the hepatic lymphatic duct (white arrowheads) are seen.

For anatomical reasons, the number of patients with chylous ascites in whom the site of leakage can be determined by lymphangiography is limited, and the type of procedure to be conducted depends on each individual case. In patients with non-chylous lymphatic ascites after iliac lymph node dissection in whom leakage can be visualized by lymphangiography from the legs, therapeutic lymphangiography and lymphatic vessel embolization are effective. In patients with lymphorrhea due to periceliac lymph node dissection in whom the leakage site can be observed by hepatic lymphangiography, therapeutic lymphangiography or embolization with NBCA may be helpful. In the event of chylous ascites, which is caused by intestinal lymphatic vessel breakdown, embolization following transvenous retrograde thoracic duct cannulation or intranodal lymphangiography may be conducted via a mesenteric lymph node, but the number of patients in whom these procedures is feasible is limited.^34–36 The diagnosis and treatment of chylous ascites is a future issue for lymphatic interventional radiology.

When conducting lymphatic intervention of the thoracic duct, knowledge of the thoracic duct and the lymphatic vessels flowing into it is essential. Around 80% to 90% of the lymph circulating in the body is believed to pass through the thoracic duct before draining into the veins.³⁷ Lymph flowing into the cisterna chyli, as the origin of the thoracic duct, comprises 40% from the hepatic lymphatic vessels, 40% from the intestinal lymphatic vessels, and 20% from the lumbar lymphatic vessels (in the legs).³⁸ What must be understood here is that almost all lymph comes from the viscera, so the hepatic and intestinal lymphatic systems are deeply involved in the conduct of lymphatic intervention. Lymphorrhea caused by the breakdown of an iliac lymphatic vessel due to intrapelvic lymph node dissection often causes no more than local compression symptoms and is unlikely to lead to a deterioration in general condition, but lymphorrhea caused by damage to an intestinal or hepatic lymphatic vessel or the thoracic duct may cause severe leakage exceeding 1 L per day, potentially leading to life-threatening conditions such as hypoalbuminemia or immunodeficiency due to lymphocyte loss.^1,2

Lipiodol has a high specific gravity and sinks to the bottom of lymphatic vessels. Even distribution is therefore not seen in the thoracic duct, with the material moving through the vessel in a sunken state. This means that even if lymphorrhea is present, Lipiodol may not reach the leakage site if the amount of leakage is small or the leak is located in a branch that branches from the ventral side of the thoracic duct. In particular, in the event of breakdown of the pulmonary lymphatic vessels that run ventrally from the thoracic duct, leakage may be observable by lymphatic duct scintigraphy, MR lymphangiography, or transcatheter thoracic ductography with water-soluble iodine contrast agent, but not on Lipiodol lymphangiography.

Postoperative chylous pleural effusion caused by damage to the thoracic duct is a known postoperative complication of surgery for esophageal cancer. In this surgery, the thoracic cavity is opened from the abdominal cavity as part of the surgical procedure. Should periceliac lymph node dissection also be performed, lymphorrhea may occur from this site. Normally, this would be expected to result in chylous ascites, but lymphorrhea may flow into the thoracic cavity, where the pressure is lower, and drain from there as chylous pleural effusion. Hepatic lymphangiography may enable observation of leakage in the periceliac region, and embolization may then be possible.

Conservative treatment is the least invasive option, but this may be risky in patients with severe chyle leakage, as described above. In this event, surgical treatment should be proactively conducted, but the general condition of the patient may be too poor to permit surgery. In such cases, percutaneous treatment in the form of lymphatic intervention can be performed less invasively. Therapeutic lymphangiography and lymphatic embolization can also be conducted repeatedly. Other possible procedures include a Denver shunt and OK-432 sclerotherapy. However, the percutaneous transabdominal approach to the thoracic duct cannot be described as low risk. Lymphatic interventional radiology has yet to gain wide adoption, and the potential complications are not yet fully known. Lymphatic interventional radiology is an effective treatment, but remains under development, and keeping an eye on new procedures, outcomes, and complications is essential.

None.

No potential conflict of interest relevant to this article was reported.