Postoperative chylothorax is a rare and refractory complication after thoracic surgery. It can lead to a large amount of nutrient loss, including protein, triglycerides, and other substances, resulting in electrolyte imbalance, malnutrition, and severe infection (1–3). Especially for patients with high-output chylothorax (> 1,000 ml/d), if treatment is ineffective, life-threatening sequelae might occur with a mortality rate of up to 50% (1–3). Conservative treatment (e.g., total parenteral nutrition, somatostatin, etc.) is the first-line choice for postoperative chylothorax (3–6). However, there are some defects when treating patients with high chyle output, such as unsatisfactory efficiency and long treatment period with poor tolerability (3–6). Surgical repair, as a salvage treatment after the failure of conservative treatment, has a high occurrence rate of secondary surgery-related complications and the risk of death (up to 38 and 25%, respectively) (4–7).

The conventional transpedal lymphangiography (TL) is a classic diagnosis method for postoperative chylothorax with a therapeutical effect. The viscous ethiodized oil injected in TL can embolize the lymphatic leakage site (8). In literature, TL was reported with an overall treatment success rate of over 50% and a complication rate of <3% when treating postoperative chylothorax (5, 7, 9). Compared to surgical repair, TL is minimally invasive and can be tolerated by critically ill patients. Therefore, TL holds the potential as second-line management where conservative treatment fails. In conventional TL, it was empirically recommended that ethiodized oil should not exceed 20 ml (5, 8–11). Nevertheless, this recommended ethiodized oil dose may be insufficient for treating high-dose postoperative chylothorax because of the poor treatment efficiency rate of 35% (5, 10). Increasing the ethiodized oil dose in TL may benefit the leakage embolization and improve treatment efficiency. So far, it still lacks objective evidence on the safety or clinical efficacy of TL treatment with high-dose ethiodized oil (> 20 ml) application in TL. This retrospective study preliminarily explored the safety and effectiveness of TL with high-dose ethiodized oil application (> 20 ml) in the treatment of high-output postoperative chylothorax when conservative treatment failed.

The median age of 7 patients (4 males and 3 females) was 62 years (range: 30–70 years). Two and 5 patients were diagnosed with esophageal carcinoma and non-small cell lung carcinoma, respectively. All patients underwent surgical tumor resection with mediastinal lymphadenectomy. After surgery, postoperative chylothorax occurred in 5 patients on the right side and 2 on the left side. TL treatment was performed at a median of 20 days (range: 15–31 days) after surgery. The median daily chyle output before TL was 1,500 ml/day (range: 1,100–2,000 ml/day). The details are shown in Table 1.

The technical success of TL was 100% (7/7). The median volume of ethiodized oil injected in TL was 27.6 ml (range: 21.2–30.0 ml) (Table 2). The median time of lymphatic opacification at the levels of knee joint space, upper femoral head, L5 vertebra, Th12 vertebra, Th5 vertebra, and the left jugular venous angle from the start of ethiodized oil injection were 4 min (range: 3–7 min) and 10 min (range: 9–12 min), 22 min (range: 15–34 min), 42 min (range: 33–51 min), 52 min (range: 47–62 min) and 69 min (53–75 min) (Table 2; Figure 2). Lymphatic duct leakage, including definite ethiodized oil extravasation out from thoracic duct in dynamic fluoroscopy and the ectopic presence of the ethiodized oil in the pleural space in chest CT after TL, was identified in 5 patients (5/7, 71%) (Table 2; Figure 2). No Adverse event of TL was recorded.

After TL, 6 patients experienced a progressive decrease of the daily chyle output. The median time for removing the thoracic drainage after TL was 7 days (range: 4–13 days). The treatment success rate of TL was 86% (6/7). One patient without significant reduction of daily chyle output after TL underwent further percutaneous afferent lymphatic vessel sclerotherapy (ALVS) on the 8th day after TL, who was cured later (11).

In this retrospective study, 5 and 2 patients had chylothorax complications after lung cancer and esophageal cancer resection, respectively, with a daily chyle output of more than 1,000 ml/d. After 15–31 days of ineffective conservative treatment, all patients received TL treatment with high-dose ethiodized oil application (>20 ml). The technical success was achieved in all patients, with the median volume of ethiodized oil injected in TL of 27.6 ml. The treatment success rate of TL was 86% (6/7). No Adverse event of TL was reported.

So far, TL has been increasingly used to manage postoperative chylothorax with a technical success rate of 95–100% (5, 6, 8, 9, 23). Except for the embolization effect, ethiodized oil can induce sterile inflammation at the fistula, beneficial for subsequent histological repair (8). However, the traditional manual injection of ethiodized oil in TL was unstable with the velocity between 0.2 and 0.5 ml/min and tiring over hours' operation (8, 21). So, we improved the injection method by connecting an infusion pump commonly used, replacing the primordial handy injection. This simple technical improvement can stabilize the injection pressure and velocity. Moreover, it benefits the standardization of TL procedure for the research purpose. For instance, the mean time of lymphatic visualization at different targets can be statistically analyzed: 10 min for superior margin of femoral head (groin region), 42 min for Th12 (cistern chyli region), and 69 min for left jugular venous angle (whole thoracic duct).

In previous studies, the ethiodized oil usage in TL was mostly around 10 ml (5, 8–11, 18, 20–22). But after accomplishment of injection, the ethiodized oil probably only reached pelvic or abdominal lymphatic vessels, so interventionalists always needed to monitor for more than 4 h until the ethiodized oil flowed into the thoracic duct (8, 11, 20–22). With the increase of ethiodized oil dose to more than 20 ml, we can visualize the left jugular vein angle as the endpoint of ethiodized oil injection, resulting in a more reliable thoracic duct embolization. It explained why the treatment success rate of TL for the high-flow postoperative chylothorax reached 86% (6/7) in our cohort, which was higher than 35% in previous reports (5, 10). Similarly, a recent report also showed that high-dose ethiodized oil (>40 ml) application in intranodal lymphangiography (INL) was feasible and safe (24). It achieved a treatment success rate of 83% without any adverse event for the treatment of high-flow postoperative chylothorax, similar to our findings (24). However, we need to point out: in INL, part of the ethiodized oil was wasted because of the extravasation from the punctured lymph node, so we can't confirm how much of the ethiodized oil genuinely entered the lymphatic system (8, 24). But in TL, the needle was fixed with suture resulting in a more reliable ethiodized oil injection without any waste, resulting in less usage of ethiodized oil than INL (21).

Nevertheless, the interventionalists need to pay attention to the risk of ectopic embolism caused by ethiodized oil. Although most ethiodized oil in TL is filtered and gradually resolved in lymph nodes, a small portion of ethiodized oil in the lymphatic vessels can enter the subclavian vein into the pulmonary circulation, which was filtered by a regular pulmonary capillary bed (25). But in patients with comorbidities, such as severe pulmonary dysfunction, pulmonary arteriovenous malformations, and right-to-left shunt heart disease, the ethiodized oil might enter systematic circulation leading to lethal cerebral embolism (11, 25, 26). So, strict clinical estimation before TL is essential.

Among the 7 patients, the lymphatic duct leakage presenting with definite ethiodized oil extravasation out from thoracic duct and the ectopic presence of the ethiodized oil in the pleural space was identified in 71% of patients (5/7), similar to 64–86% reported in the literature (10, 14, 21, 27). It implied an iatrogenic injury of the thoracic duct in the prior surgeries. Chest CT after TL is routinely performed in our cohort because it has higher diagnostic sensitivity for leakage site identification than fluoroscopy. It can provide more explicitly anatomical details of the lymphatic system (20, 28, 29). If TL treatment fails, these CT data can also assist in planning further lymphatic interventional therapies, such as ALVS mentioned above and thoracic duct embolization (8, 9, 11, 20, 22).

This study has limitations. First, the sample size is minimal. Second, it lacks a comparison to conventional TL with ethiodized oil usage of <20 ml. In the cases with high-dose postoperative chylothorax (>1,000 ml/d), conventional TL showed a poor efficiency rate of about 35%, so it was rarely solo performed (5, 10). Instead, conventional TL with percutaneous lymphatic intervention (e.g., thoracic duct embolization or ALVS) was the optimal choice with a higher efficiency rate of 75–100% (9). However, by comparing the literature, the results of our study suggest that TL with high-dose ethiodized oil application probably has a better therapeutic effect.

In summary, the results in this preliminary study suggest TL with high-dose ethiodized oil is a feasible, safe, and effective method for treating high-flow postoperative chylothorax. It holds the potential as the second-line choice when conservative treatment fails. Besides, this study works out stable ethiodized oil injection using a commonly used infusion pump, advantaging TL performance.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Ethics Committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. The patients/participants provided their written informed consent to participate in this study.

FP, LL, and XW contributed to the conception, design of the study, and wrote sections of the manuscript. WZ, DL, and LY collected, analyzed, and interpreted the data. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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