In thoracic esophagectomy, chylothorax is usually the result of unrecognized surgical injury to the main or branches of thoracic duct. Postoperative chylothorax is mostly an uncommon complication of esophagectomy and occurs only in 0.6% to 4.0% of esophagectomy (1-6). In thoracic esophagectomy, complications of chylothorax resulted in hypoproteinemia, lipid loss, and respiratory failure due to atelectasis (7-9).
In previous studies which included only a small number of patients and had variable results, risk factors and its optimal treatments strategies were discussed. Although there are several approaches regarding the best clinical practice toward postoperative chylothorax (10,11), the most common initial management approach is conservative treatment with thoracic drainage together with total parental nutrition. However, conservative treatment could be effective only for minor chyle leakage, with significant amount of effusions lasting for several weeks. Moreover, in case with the amount of pleural effusion is excessive and prolonged, such conservative treatment is unlikely to succeed.
There are several risk factors for the postoperative chylothorax after esophagectomy. Most of these reported risk factors were somewhat related with the vulnerability and misidentification of thoracic duct. Regarding the non-invasive treatment strategy, somatostatin (12,13) and its synthetic analogue octreotide (14) has been successfully tried to treat postoperative chylothorax in adults and children (9). The clinical efficacy of octreotide for treating postoperative chylothorax in thoracic esophagectomy for esophageal cancer has well examined (15). Moreover, recent research demonstrated that thoracic duct lymphangiography and subsequent embolization (TDE) was effective treatment strategy for postoperative chylothorax after esophagectomy.
The clinical manifestations of chylothorax after esophagectomy
Chylothorax after esophagectomy is not uncommon but potentially critical complication, with previous reported incidence of 0.4–4% (16,17). Some reports demonstrated higher incidences of thoracic duct injury with transhiatal approach in the comparison with transthoracic esophagectomy, whereas other reports demonstrated almost equal incidence of chylothorax regardless the surgical approach. In our institution, 3.8% of patients were diagnosed as postoperative chylothorax after thoracic esophagectomy among 521 patients regardless the thoracic approach (18).
The amount from chest drain is the initial sign to the diagnosis of chylothorax. Injury of thoracic duct or its tributaries usually shows in the early postoperative day as an excessive amount of fluid or cream-colored liquid from the chest tube. Physical and biochemical character of this specific sign help to differentiate between chylous from non-chylous fluid. It has been reported that there are rich in lymphocyte, fat and triglycerides in chyle. Usually, the levels of triglyceride are known less than 50 mg/dL in non-chylous fluid, whereas the level of triglycerides are higher than 110 mg/dL in the fluid in cases of chylothorax.
Chylothorax usually related to injury to main thoracic duct or its tributaries. Physiologically, thoracic duct is known to transport up to 4,000 mL/day of chyle, where rich in fluid, protein, lymphocytes, and lipid (19). Therefore, prolonged loss of chyle can result in hypovolemia, malnutrition, which lead negative impact on postoperative course after esophagectomy. Thus, chylothorax was related with higher rates of infectious complications and arrhythmia, resulted in a longer hospital stay. Previous reports revealed that chyle leakage could lead to pneumonia (20) and possible associated with surgical site infections.
Risk factors for postoperative chylothorax after esophagectomy
There have been several reports demonstrated the risk factors for chylothorax after esophagectomy. Miao et al. demonstrated that patients with body mass index (BMI) less than 25 had a risk for chylothorax in thoracic esophagectomy (20). However, risk of BMI has not been fully discussed. Recent meta-analysis investigated on BMI reported opposite results. Patients with high BMI was associated with a decreased incidence of chylothorax in esophagectomy (21). A possible explanation of decreased incidence is possible protection effect of fatty tissue surrounding the tumor and esophagus. More fatty tissue could result in better protection of thoracic duct during surgery.
Esophageal squamous cell carcinoma (SCC) was reported to be another risk factor for postoperative chylothorax (17). In that report, the incidence of chylothorax in histological type SCC was 2.7% in comparison with that of chylothorax in adenocarcinoma was 0%. Another report using multivariate analysis also suggested that SCC histological type, body mass index and age-adjusted Charlson Comorbidity Index score were independent risk for postoperative chylothorax (17). However, we could not claim clear conclusion due to the small number of patients in this study.
The oncological and anatomical factors were reported as possible risk for postoperative chylothorax. Certain tumor location and extent and location of lymph node metastasis were identified as risk factors in previous studies. Indeed, recent report suggested that difficult mediastinal dissection during esophagectomy in middle thoracic esophageal cancer may lead to risk to thoracic duct injury, which support above hypothesis.
On the other hand, based on the analysis with dominant histological type of SCC, post-chemoradiotherapy and higher amount of intraoperative fluid balance are possible predictors of chylothorax in esophagectomy (22). Regarding intraoperative fluid balance, there were certain consideration about the reason. Most of the reason of typical severe chylothorax to be intraoperative damage of the main stream of thoracic duct or rupture of thoracic duct at thoracic duct. Intraoperative higher infusion volume could induce the status of more risk to be rupture thoracic duct in patients with fragile tissue in case of post-chemoradiation.
Efficacy of octreotide for postoperative chylothorax
Octreotide has been reported to be a possible, effective treatment for chylothorax after thoracic surgery. Octreotide is a somatostatin analogue with antisecretory properties similar to those of somatostatin (23). Octreotide has inhibitory actions by the releasing various hormones, such as insulin and on lymph fluid excretion (23). In previous studies, somatostatin markedly compress the diameter and decreased the flow of thoracic duct (24). Rimensberger et al. firstly reported that clinical efficacy of somatostatin to treat chylothorax (13). After this report, subsequent clinical trials suggested that octreotide was effective for primary chylothorax or surgically-related chylothorax in children (25). In adults, recent study revealed the efficacy of octreotide for postoperative chylothorax after thoracic surgery in adults, particularly after esophagectomy (18). In this study, octreotide treatment effectively decreased chest drain output and chest drains could be removed in 86.6% of patients. Importantly, treatment was successful for 50% of patients with drain amount before treatment that exceeded 1 L daily. Therefore, the former recommendation that surgical ligation is necessary if the amount of chest drain output is more than 1 L/day may need to be reconsidered in view of the efficacy of octreotide.
Because the treatment with octreotide is safe and non-invasive, it could be considered as a first-line treatment for postoperative chylothorax in esophagectomy. However, there are potentially other invasive effective option, such as thoracic duct embolization.
Efficacy of thoracic duct embolization for postoperative chylothorax
Thoracic duct lymphangiography with embolization (TDE) is a novel, less invasive, and potentially equally efficacious treatment method. Cather cannulation and embolization technique used by Cope (26) to treat chylothorax was effective in patients with thoracic duct laceration. However, its reproducibility and success rates have not high and varied in different reports. Recent report demonstrated thoracic duct embolization or disruption with very good effect in patients with chyle leak after thoracic surgery (27). Subsequently, Litherland et al. described case report where CT guided disruption of the lymphatics had good effect in the management of high output chylothorax (28). Moreover, Asian group performed lymphangiography on patients that were unlikely to respond to conservative measures. They found that lymphangiography not only identified the site of the leak but also led to successful treatment of leak in all cases (29). Taken together, these reports commend early lymphangiography in cases with postoperative chylothorax which unlikely to be cured by conservative treatment.
The safety and feasibility of percutaneous thoracic duct embolization or interruption have been reported. Recent report reviewed the existing literatures on percutaneous embolization treatment of chylothorax (30). The authors found 5 case series and 3 case reports inclusive of ninety patients in whom percutaneous embolization treatment for chylothorax was attempted between 1998 and 2004. Percutaneous embolization resulted in success in 69% of the cases. This report concluded that percutaneous embolization treatment for chyle leak is safe and feasible, with low morbidity rates and satisfactory results. Another review paper investigated the indications, technical approach, and clinical outcomes of percutaneous embolization treatment for thoracic duct in 105 patients with postoperative chylothorax (31). The overall success treatment rate of this procedure was satisfactory in this series (79%). Thus, the report concluded that percutaneous embolization techniques are safe and effective as first-line minimally invasive treatments for thoracic duct injuries after surgery.
Thoracic duct embolization is relative reproductive, and its success rate is satisfactory (60–70%), there this procedure should be considered before the surgical ligation procedure.
In conclusion, although incidence of chylothorax is relatively low, surgeons have to be careful during surgery particularly patients with their tumor or lymph nodes closely located to the main stream of thoracic duct. In case with chylothorax, prompt diagnosis and the optimal treatment strategy is required. If the initial conservative treatment such as administration of octreotide is not effective with any chylous output is large and persistent, percutaneous thoracic duct embolization should be considered, before the surgical ligation of thoracic duct.
We thank the members of the Division of Gastrointestinal Oncology for their critical discussion of this study. We also appreciate the members of the Division of Clinical Radiology for providing us with information about the imaging examinations.
Conflicts of Interest: The authors have no conflicts of interest to declare.
- Rizk NP, Bach PB, Schrag D, et al. The impact of complications on outcomes after resection for esophageal and gastroesophageal junction carcinoma. J Am Coll Surg 2004;198:42-50. [Crossref] [PubMed]
- Bolger C, Walsh TN, Tanner WA, et al. Chylothorax after oesophagectomy. Br J Surg 1991;78:587-8. [Crossref] [PubMed]
- Alexiou C, Watson M, Beggs D, et al. Chylothorax following oesophagogastrectomy for malignant disease. Eur J Cardiothorac Surg 1998;14:460-6. [Crossref] [PubMed]
- Dugue L, Sauvanet A, Farges O, et al. Output of chyle as an indicator of treatment for chylothorax complicating oesophagectomy. Br J Surg 1998;85:1147-9. [Crossref] [PubMed]
- Dougenis D, Walker WS, Cameron EW, et al. Management of chylothorax complicating extensive esophageal resection. Surg Gynecol Obstet 1992;174:501-6. [PubMed]
- Orringer MB, Marshall B, Iannettoni MD. Transhiatal esophagectomy for treatment of benign and malignant esophageal disease. World J Surg 2001;25:196-203. [Crossref] [PubMed]
- Tachibana M, Kinugasa S, Yoshimura H, et al. Clinical outcomes of extended esophagectomy with three-field lymph node dissection for esophageal squamous cell carcinoma. Am J Surg 2005;189:98-109. [Crossref] [PubMed]
- Dubin PJ, King IN, Gallagher PG. Congenital chylothorax. Curr Opin Pediatr 2000;12:505-9. [Crossref] [PubMed]
- Beghetti M, La Scala G, Belli D, et al. Etiology and management of pediatric chylothorax. J Pediatr 2000;136:653-8. [Crossref] [PubMed]
- Wasmuth-Pietzuch A, Hansmann M, Bartmann P, et al. Congenital chylothorax: lymphopenia and high risk of neonatal infections. Acta Paediatr 2004;93:220-4. [Crossref] [PubMed]
- Cerfolio RJ. Chylothorax after esophagogastrectomy. Thorac Surg Clin 2006;16:49-52. [Crossref] [PubMed]
- Nair SK, Petko M, Hayward MP. Aetiology and management of chylothorax in adults. Eur J Cardiothorac Surg 2007;32:362-9. [Crossref] [PubMed]
- Rimensberger PC, Muller-Schenker B, Kalangos A, et al. Treatment of a persistent postoperative chylothorax with somatostatin. Ann Thorac Surg 1998;66:253-4. [Crossref] [PubMed]
- Cheung Y, Leung MP, Yip M. Octreotide for treatment of postoperative chylothorax. J Pediatr 2001;139:157-9. [Crossref] [PubMed]
- Fujita T, Daiko H, Nishimura M. Early enteral nutrition reduces the rate of life-threatening complications after thoracic esophagectomy in patients with esophageal cancer. Eur Surg Res 2012;48:79-84. [Crossref] [PubMed]
- Lagarde SM, Omloo JM, de Jong K, et al. Incidence and management of chyle leakage after esophagectomy. Ann Thorac Surg 2005;80:449-54. [Crossref] [PubMed]
- Shah RD, Luketich JD, Schuchert MJ, et al. Postesophagectomy chylothorax: Incidence, risk factors and outcomes. Ann Thorac Surg 2012;93:897-903. [Crossref] [PubMed]
- Fujita T, Daiko H. Efficacy and predictor for octreotide treatment for postoperative chylothorax after thoracic esophagectomy. World J Surg 2014;38:2039-45. [Crossref] [PubMed]
- Paes ML, Powell H. Chylothorax: An update. Br J Hosp Med 1994;51:482-90. [PubMed]
- Miao L, Zhang Y, Hu H, et al. incidence and management of chylothorax after esophagectomy. Thorac Cancer 2015;6:354-8. [Crossref] [PubMed]
- Zhang SS. The impact of body mass index on complication and survival in resected oesophageal cancer: A clinical-based cohort and meta-analysis. Br J Cancer 2013;109:2894-903. [Crossref] [PubMed]
- Ohkura Y, Ueno M, Shindoh J, et al. Risk factors for postoperative chylothorax after radical subtotal esophagectomy. Ann Surg Oncol 2018;25:2739-46. [Crossref] [PubMed]
- Lamberts SW, van der Lely AJ, de Herder WW, et al. Octreotide. N Engl J Med 1996;334:246-54. [Crossref] [PubMed]
- Markham KM, Glover JL, Welsh RJ, et al. Octreotide in the treatment of thoracic duct injuries. Am Surg 2000;66:1165-7. [PubMed]
- Kelly RF, Shumway SJ. Conservative management of postoperative chylothorax using somatostatin. Ann Thorac Surg 2000;69:1944-5. [Crossref] [PubMed]
- Cope C. Diagnosis and treatment of postoperative chyle leakage via percutaneous transabdominal catheterization of the cisterna chyli: a preliminary study. J Vasc Interv Radiol 1998;9:727-34. [Crossref] [PubMed]
- Boffa DJ, Sands MJ, Rice TW, et al. A critical evaluation of a percutaneous diagnosis and treatment strategy for chylothorax after thoracic surgery. Eur J Cardiothorac Surg 2008;33:435-9. [Crossref] [PubMed]
- Litherland B, Givens M, Lyon S. Percutaneous radiological management of high-output chylothorax with CT-guided needle disruption. J Med Imaging Radiat Oncol 2008;52:164-7. [Crossref] [PubMed]
- Matsumoto T, Yamagami T, Kato T, et al. the effectiveness of lymphangiography as a treatment method for various chyle leakages. Br J radiol 2009;82:286-90. [Crossref] [PubMed]
- Marcon F, Irani K, Aquino T, et al. Percutaneous treatment of thoracic duct injuries. Surg Endosc 2011;25:2844-48. [Crossref] [PubMed]
- Pamarthi V, Stecker MS, Schenker MP, et al. Thoracic duct embolization and disruption for treatment of chylous effusion: experience with 105 patients. J Vasc Interv Radiol 2014;25:1398-404. [Crossref] [PubMed]