Intranodal lipiodol injection for the treatment of chyle leak in children – a preliminary experience

Abstract

Objective:

To assess the effectiveness of intranodal lymphangiography using ethiodised oil (Lipiodol; Guerbet Japan, Tokyo, Japan) for the treatment of refractory cases of chylothorax and chylous ascites in the paediatric population.

Methods:

Between 2016 and 2020, eight children having chyle leak resistant to conservative management underwent intranodal lymphangiography using lipiodol injection. After ethical approval by the Institutional Review Board, these patients’ data were retrospectively analysed. Technical success was defined by opacification of inguinal and retroperitoneal lymphatics while injection on fluoroscopy. Clinical success was defined as progressively decreasing drain output and eventual cessation of output within a week after the procedure. Long-term follow up was done as feasible.

Results:

Technical success was achieved in all the patients. Complete cessation of drain output was noted within 1 week of procedure in all patients indicating clinical success. One patient had recurrence of chylous leakage after an interval of 1 month and intranodal lymphangiography was repeated for that patient. The child had technical as well as clinical success after the repeat procedure. Hence a total of 9 procedures were performed in 8 patients.

Conclusion:

Intranodal lymphangiography may prove to be a valuable minimally invasive therapeutic tool in cases of refractory chylous leakage in paediatric patients with minimal risk of complications.

Advances in knowledge:

Intranodal lymphangiography using lipiodol may prove to be a minimally invasive alternative in paediatric patients with refractory lymphatic leaks.

Introduction

Chylothorax and chylous ascites are rare accumulations of lipid-rich fluid in the pleural and peritoneal cavity, respectively, and occur as a result of lymphatic leakage. ^1–3 They are uncommonly reported in children with variable underlying aetiologies. ⁴ Congenital chylous leakage may result from lymphatic malformations or is associated with syndromes like Down, Turner and Noonan. Other aetiologies include iatrogenic or other trauma, neoplasms, infections or haemodynamic changes due to liver cirrhosis or cardiac causes. ^5–7 Diagnosis is usually made with a drain output having a milky appearance and high concentrations of triglycerides and low-density lipoproteins on biochemical analysis.

The initial management of chylous leak consists of medical measures including a low-fat diet with medium-chain triglyceride supplements, total parenteral nutrition, somatostatin analogues like octreotide and drainage of chylous fluid with administration of chemical sclerosants. ^4,8 These conservative measures have been reported to be successful in 66–77% of patients. ⁹ However, in cases of persistent or high-output lymphatic leak, these measures are likely to fail. Refractory chylous leak can lead to significant complications like lymphocytopenia, malnutrition, and recurrent infections due to secondary immunodeficiency and consequent increase in post-operative recovery time. ⁹ Although surgical management like primary repair of large lymphatic leaks and pleural- or peritoneo-venous shunting can be undertaken in refractory cases; these procedures are technically challenging, cause significant morbidity and may be futile in cases of leakage from small retroperitoneal and pelvic lymphatics. ^9–11 Recently, less invasive treatments like percutaneous thoracic duct embolisation with glue or coils and needle disruption techniques have also been reported. ^12,13

Ultrasound-guided intranodal lymphangiography is a relatively recently described minimally invasive technique for the diagnosis as well as treatment of lymphatic leaks. ¹⁴ Therapeutic effect of lipiodol has been attributed to its embolic properties leading to its accumulation at the site of leakage both outside and within the lymphatics. This is followed by a local inflammatory granulomatous reaction causing fibrosis. ^9,15 Major complications of lipiodol injection described in literature include pulmonary and systemic embolization of oil droplets. Pulmonary oil embolization is usually clinically asymptomatic unless there is an underlying severe cardiopulmonary disease. Embolization into brain or renal circulation can occur in patients with right-to-left cardiac shunts or patent lymphovenous connections, leading to severe consequences. However, clinically significant oil embolization following intralymphatic lipiodol injection has been shown to be associated with usage of higher volumes of lipiodol, typically >20 ml or >0.25 mL/kg body weight. ^16,17

The use of lymphangiography as a therapeutic modality has previously been described in adults. ^18–20 However, there is only sparse literature on the utility of this technique in the paediatric population. ^21–23 In this study, we assessed the effectiveness of intranodal lymphangiography using ethiodised oil (Lipiodol; Guerbet Japan, Tokyo, Japan) for the treatment of refractory cases of chylothorax and chylous ascites in the paediatric population.

Methods and materials

Between 2016 and 2020, eight children having chyle leak resistant to medical management were referred to our department for intranodal lymphangiography. After ethical approval by the Institutional Review Board, these patients’ data were retrospectively analysed for this study.

Our study group consisted of seven boys and one girl with an age range of 2–13 years (median, 5 years). Four patients had chylothorax and four had chylous ascites. Three of these patients developed chylous leakage as a post-surgical complication after excision of intraabdominal lymphatic malformation, left adrenal neuroblastoma and Glenn procedure, one case was secondary to mediastinal fibrosis due to tubercular infection, one case was chylothorax associated with Trisomy 21 and three cases were idiopathic with no underlying syndromic association. Intranodal lymphangiography was preceded by conservative medical treatment (dietary fat restriction, octreotide and fluid drainage) for a period of 6 to 10 weeks (depending on output volume and general condition of the patient) in these patients which had failed to resolve the chylous leak in all these cases. In all patients, attempts were made to localize the leak by either performing preprocedural MR lymphangiography (MRL) (seven patients) or lymphoscintigraphy (one patient). MRL study consisted of standard T1W, heavily T2W fat-saturated sequences and T1 fat saturated gradient echo sequence after bilateral intranodal diluted gadolinium contrast injection (Figure 1). The lymphatic leak was visualized on lymphoscintigraphy in one patient with chylous ascites and in four out of seven patients who underwent MRL. However, intranodal lymphangiography was performed in all the patients as an attempt to reduce chylous output. Significant right-to-left shunting was excluded in all patients with transthoracic echocardiography in all patients before the procedure.

Figure 1.

Intranodal MR lymphangiography image (a) shows pooling of contrast from thoracic duct in the prevertebral region (arrow) [HP: right hydropneumothorax; RL – right lung with collapse and consolidation]. Delayed MR lymphangiography image (b) shows contrast leak into right hemithorax increasing the intensity of fluid (arrows)

The intranodal lipiodol injection procedure was done under sedation in a fluoroscopy suite in all but one patient in whom the procedure was performed in the operation theatre. Under aseptic conditions and ultrasound (USG) guidance, the largest lymph node in the inguinal region was punctured with a 25-gauge needle. The tip of the needle was carefully positioned at the cortico-medullary junction of the lymph node. After ascertaining the needle position on USG, the injection of Lipiodol was performed under serial intermittent fluoroscopic guidance. Lipiodol injection was done at an extremely slow rate in order to prevent perinodal extravasation. A total volume of 0.1–0.15 mL/kg lipiodol was injected over a period of 10 min, maximum dose limited to 10 ml. The same procedure was followed on the inguinal lymph node of the opposite side (Figure 2). In one patient in whom the procedure was performed in the operation theatre, the visualised small inguinal node (approximately 3 mm) could not be punctured under USG guidance. Hence, the procedure could not be successfully completed in the fluoroscopy suite. This patient had enlarged nodes in the retroperitoneum and the left common iliac location. The left common iliac node was punctured after the area was surgically exposed in the operation theatre (Figure 3). The rest of the procedure was similar to what has been described above. The total duration of the procedure ranged from 30 to 45 min.

Figure 2.

Fluoroscopic image obtained during the intranodal injection of lipiodol showing opacification of bilateral inguinal and pelvic lymph nodes and lymphatics (arrows) [N: needle placed in the left inguinal node]

Figure 3.

Intraoperative photograph (a) showing injection of lipiodol in to the left common iliac nodes after surgical exposure. (b,c) Intraoperative fluoroscopy showing opacification of retroperitoneal lymphatics (arrows). No further passage of contrast via cisterna chyli is noted proximally. The presence of stasis near the suspected site of injury (lower most surgical stapler) is an indirect sign of the leak being sealed by Lipiodol

Technical success of the procedure was defined by opacification of inguinal and retroperitoneal lymphatics while injection on fluoroscopy. The procedure was continued until administration of total volume of lipiodol was complete. No other embolising agent was used. A follow-up radiograph (7 patients) was performed the next day to visualise the distribution of lipiodol. In one of the patients who had previously undergone excision of an abdominal lymphatic malformation, there was atypical distribution of lipiodol as visualised during the procedure under fluoroscopy. Thus, a CT scan was performed to confirm the distribution of lipiodol and its leak (Figure 4).

Figure 4.

Axial (a) and coronal (b) post-procedure CT scan MIP images in same patient as Figure 2 showing distribution of lipiodol in retroperitoneal and thoracic lymphatics as well as leakage into bilateral pleural cavity

The drain output volume was evaluated for 3–4 days post-procedure. Clinical success was defined as progressively decreasing drain output and eventual cessation of output within a week after the procedure. Long-term follow up of the patients was done as feasible, to note any recurrence of chylous leakage.

Results

Technical success was achieved in all the patients. Complete cessation of drain output on post-procedure evaluation was noted in all patients indicating clinical success. Seven out of eight patients did not show recurrence of chyle leak on follow-up (1 to 5 years of follow-up; median duration of 2 years). One patient developed recurrence of chylothorax a month after the procedure. The child had a complete atrioventricular canal defect with right ventricular hypoplasia, had undergone Glenn procedure and was awaiting corrective Fontan surgery when he developed chylothorax. Although lymphangiography was repeated for the recurrence and chylothorax responded well to it, the child unfortunately succumbed within a few weeks following the procedure due to his uncorrected congenital heart disease. No periprocedural complications were seen in our patients.

Hence, a total of nine procedures were performed in eight patients. Clinical and procedure details of the patients are summarised in Table 1.

Table 1.

Patient characteristics and procedure details

Patient No.	Chyle leak	Age (in years)	Sex	Primary diagnosis	Treatment history	Technical success	Clinical success	Duration of follow-up (in years)	Follow-up	Comments
1	Chylous ascites	7	Male	Intraabdominal lymphangioma	Lymphangioma excision	Yes	Yes	5	No recurrence
2	Chylous ascites	2	Male	Left adrenal neuroblastoma with local recurrence	Excision of the recurrent lesion	Yes	Yes	4	No recurrence	Inguinal nodes were too small to target. Procedure was performed on left common iliac nodes in the operation theatre.
3	Chylothorax	6	Male	Atrio-ventricular canal defect	Glenn procedure	Yes	Yes	3	Recurrence after first procedure	Underwent procedure twice. Child succumbed to heart disease after clinical success
4	Chylothorax	13	Female	Mediastinal fibrosis	Antitubercular treatment	Yes	Yes	2	No recurrence
5	Chylous ascites	9	Male	Idiopathic	None	Yes	Yes	2	No recurrence
6	Chylothorax	3	Male	Down’s syndrome	None	Yes	Yes	1.5	No recurrence
7	Chylothorax	4	Male	Idiopathic	None	Yes	Yes	1.5	No recurrence
8	Chylous ascites	4	Male	Idiopathic	None	Yes	Yes	1	No recurrence

Discussion

This study highlights the effectiveness of intranodal lymphangiography as a minimally invasive alternative to complex surgical procedures for treating patients of chylous leakage resistant to conservative treatment.

Ultrasound-guided intranodal lymphangiography could be performed successfully in all the patients. In contrast to the more invasive conventional pedal lymphangiography, intranodal lymphangiography uses ultrasound guidance for direct needle access to inguinal lymph nodes, requires no incision and by-passes lower limb lymphatics markedly decreasing the procedure time, injectate volume and radiation dose to the patient. These advantages make this technique more appealing for use in the paediatric population. In their study, Rajebi et al reported successful completion of intranodal lymphangiography in four out of five paediatric patients. ²⁴ One procedure was terminated owing to excessive patient motion and resultant perinodal extravasation. In our study, all procedures were done under sedation and meticulous attention was paid to proper positioning of the needle at the cortico-medullary junction of the lymph node and a very slow rate of manual lipiodol injection was performed to prevent perinodal extravasation in order to ensure maximum infusion into the lymphatics. As described in one of the patients in this study, in the rare scenario of inguinal lymph nodes being too small to be targeted under USG guidance, more invasive options like pedal lymphangiography and surgical exploration of retroperitoneal nodes have to be considered.

In our study, good clinical response was seen in all cases post-procedure in the form of dramatic cessation of drain output. Curative effect of lipiodol in cases of refractory lymphatic leaks has been reported previously in adults with a success rate of 51–100%. ^18–20 An interesting observation made by Kawasaki et al was that a 100% success rate could be achieved in the niche patient group of minor lymphatic leaks. However, in the paediatric population, only few case reports are available describing the therapeutic role of lymphangiography. ^21–23 To our knowledge, ours is the largest series of pediatric cases in this regard.

On follow-up, out of eight patients in our study, one patient developed recurrence of chylothorax a month after the procedure. There were no periprocedural complications in our patient cohort. Apart from the inherent risk of local site pain and lipiodol extravasation, serious complications reported with lipiodol injection are symptomatic pulmonary embolism in patients with underlying respiratory compromise and cerebral embolism in cases of right-to-left cardiac shunts. ^16,25,26 Since these complications are directly related to the volume of lipiodol injection, their risk is particularly low with smaller volumes as used in our study. ^16,17 However, since these complications can lead to devastating consequences for the patient, utmost care was taken to avoid inadvertent intravenous or intraarterial injection of lipiodol or usage of excessive lipiodol volume.

Percutaneous transabdominal or translumbar access to thoracic duct followed by embolisation with glue or coils is another minimally invasive fluoroscopic technique which has been described for treatment of chyle leakage. However, there are some major differences when compared to intranodal lipiodol injection – percutaneous access to thoracic duct is a technically demanding procedure and depends significantly on the thoracic duct anatomy; it is a feasible treatment option only in cases of chylothorax; however, intranodal lipiodol injection has proven useful for both abdominal and thoracic lymphatic leakages. ²⁷ Also, thoracic duct embolisation generally has a longer fluoroscopic procedural time as compared to intranodal lipiodol injection. There are a few limitations in our study and one of the main limitations is the small sample size precluding meaningful statistical analysis. Small sample size is because of the rarity of refractory chyle leaks. Ours is a retrospective study with no defined study protocol leading to loss of patient information like comparable intervals of post-procedure evaluation. The study did not have a control group of patients undergoing surgical correction instead of lymphangiography for comparison. Another limitation is that patients in this study had a wide variety of pre-procedure illnesses which might have influenced the outcome. Further studies with larger sample size are required.

In conclusion, intranodal lymphangiography may prove to be a valuable minimally invasive therapeutic tool in cases of refractory chylous leakage in paediatric patients with minimal risk of complications.