- Email: [email protected]
Medical and Surgical Management of Chylothorax and Associated Outcomes
CLINICAL INVESTIGATION
Medical and Surgical Management of Chylothorax and Associated Outcomes Fabien Maldonado, MD, Rodrigo Cartin-Ceba, MD, Finn J. Hawkins, MBBCh and Jay H. Ryu, MD
Abstract: Chylothorax is an uncommon form of pleural effusion that can be associated with traumatic and nontraumatic causes. Optimal management and outcome for patients with chylothorax remain unclear. This retrospective single-center study assessed the modes of management for chylothorax in 74 adult patients (ⱖ18 years old) and associated outcomes. The role of lymphangiographic imaging was also evaluated. Initial treatment approach was nonsurgical in 57 patients (77%) but a surgical procedure (pleurodesis, thoracic duct ligation, and/or surgical repair) was eventually performed in 44 patients (59%). The rate of resolution with initial treatment measures was significantly worse for patients with nontraumatic chylothorax compared with those with traumatic causes (27% versus 50%, P ⫽ 0.048). Even after additional therapeutic maneuvers including surgery, chylous effusion recurred more commonly in nontraumatic chylothorax when compared with the traumatic group (50% versus 13%, respectively, P ⬍ 0.001). Lymphatic imaging did not seem to materially influence management. Nonsurgical approaches may lead to resolution of the chylothorax in nearly one half of patients with traumatic chylothorax but in only a minority of those with nontraumatic chylothorax. The majority of patients with nontraumatic chylothorax will eventually require surgical maneuvers, but one third of such patients still fail to resolve their chylothorax. Key Indexing Terms: Chylothorax; Pleural effusion; Pleurodesis; Thoracic duct ligation. [Am J Med Sci 2010;339(4):314–318.]
C
hylothorax is an uncommon type of pleural effusion defined by the presence of chyle in the pleural space.1,2 Chyle is a complex fluid of intestinal origin and composed of lipids, electrolytes, proteins, and lymphocytes (primarily T lymphocytes). The cisterna chyli, located anterior to the first or second lumbar vertebrae, mark the beginning of the thoracic duct, the main lymphatic vessel responsible for the transport of chyle from the abdominal cavity to the central venous system. The thoracic duct enters the thoracic cavity through the aortic hiatus, runs along the right of the thoracic spine, posterior to the esophagus, and crosses the midline between the fourth and sixth thoracic vertebrae level before entering the left internal jugular or subclavian vein in the superior mediastinum. Although considerable variations exist, this anatomy explains the preferential lateralization of chylous effusions depending on the level of thoracic duct injury or obstruction.1,3,4
Division of Pulmonary and Critical Care Medicine (FM, RC-C, JHR), Mayo Clinic, Rochester, Minnesota; and Mayo Graduate School of Medicine (FM, RC-C, FJH), Mayo Clinic, Rochester, Minnesota. Submitted October 2, 2009; accepted in revised form November 25, 2009. This study was supported by Mayo Clinic Foundation. The authors report no potential conflict of interest. Correspondence: Fabien Maldonado, MD, Division of Pulmonary and Critical Care Medicine, Gonda 18 South, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905 (E-mail: [email protected]).
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The diagnosis of chylothorax is sometimes straightforward, especially after chest trauma or surgical procedures, for example, esophagectomy, well known to be associated with the development of chylothorax.5 It can be more difficult to recognize in nontraumatic contexts. A delay in diagnosis can occur as the gross appearance and even biochemical properties of chylous pleural fluid may be altered by multiple factors, such as the nutritional status of the patient and concomitant illnesses.6,7 Prolonged chylous fluid drainage may result in malnutrition, immunocompromised state, and severe electrolyte abnormalities, potentially contributing to increased morbidity and mortality.1,2 Differing management strategies have been described over the years. Although attempts at a more systematic approach to treating chylothorax have been presented, the evidence for such recommendations remains scarce, including the absence of controlled clinical trials, largely because of the uncommon occurrence of this disorder.1,8 –14 We recently published data on the biochemical characteristics of chylous pleural effusions based on a retrospective review of 74 cases encountered over a 10-year period at our tertiary referral medical center.7 In this study, we report on the management aspects of these patients with respect to types of treatment, complications, and associated outcome. We also assess the clinical impact of lymphangiographic or lymphoscintigraphic data.
METHODS Study Subjects We conducted a computer-assisted search of electronic medical records at the Mayo Clinic, Rochester, MN, from January 1, 1997, through December 31, 2006, and identified a cohort of 74 adult patients (ⱖ18 years old) diagnosed with chylothorax as evidenced by the presence of chylomicrons in the pleural fluid. The biochemical characteristics (including triglyceride, lactate dehydrogenase, protein, and cholesterol levels) of the pleural fluid have been presented in a previous report.7 Clinical Data Medical records were carefully examined and the following data were retrieved: age, sex, cause of chylothorax (as assigned by consensus of 2 of the authors, FM and JHR), amount of pleural fluid drainage per day, initial treatment and response, other treatments including type of surgical treatment when applicable, time to resolution of chylothorax, time to recurrence, complications, and mortality. We also reviewed lymphangiography and lymphoscintigraphy data, when available, and evaluated impact on management and outcome. Success in the management of chylothorax was defined by resolution of the pleural effusion without documented recurrence in the follow-up period.
The American Journal of the Medical Sciences • Volume 339, Number 4, April 2010
Management of Chylothorax
TABLE 1. Initial interventions and associated outcomes for patients with traumatic chylothorax (n ⫽ 40) Mode of management Dietary measures onlya Thoracentesis only Dietary measures and thoracentesis Chest tube drainage alone Dietary measures and chest tube drainage Dietary measures and surgical pleurodesis Thoracic duct ligation Surgical pleurodesis and thoracic duct ligation Overall a
No. patients (%)
Success rate (%)
4 (10) 3 (8) 2 (5)
50 66 50
3 (8) 23 (58)
67 43
1 (3)
100
1 (3) 3 (8)
100 33
40 (100)
50
One of these patients also received octreotide therapy.
Statistical Analyses Continuous data are presented as median and range, when appropriate, and percentages for categorical variables. Continuous data were analyzed using Wilcoxon rank-sum test and 2 or Fisher exact test for categorical variables as appropriate. In all cases, a P-value ⬍0.05 was considered significant (2-tailed).
RESULTS There were 37 men (50%) and 37 women (50%). The median age was 61.5 years (range, 20 –93 years). Pleural effusion was unilateral in 58 patients (78%) and involved the right hemithorax in 39 patients (67%) and left hemithorax in 19 patients (33%). Pleural effusion was bilateral in the remaining 16 patients (22%). Of the 74 cases of chylothorax analyzed, 40 (54%) were associated with a traumatic (surgery or invasive procedure) cause and 34 (46%) were nontraumatic or idiopathic in origin. The traumatic group included 39 patients who developed chylothorax as a result of surgery (mostly esophageal, pulmonary, or cardiac); 1 remaining patient had thrombosis of a central vein after central venous cannulation. Nontraumatic causes included 9 lymphoproliferative disorders, 5 portal hypertension from cirrhosis or pancreatic cancer, 3 radiation-related injuries, 3 primary lymphatic disorders, 3 solid tumors, 2 thoracic duct obstruction from subclavian thromboses (idiopathic and secondary to thoracic outlet syndrome, respectively), and 1 case each of lymphangioleiomyomatosis and amyloidosis. No cause was identifiable in 7 remaining cases. Traumatic Chylothorax The types of initial treatment and respective outcomes are summarized in Table 1. Most patients (35 of 40, 88%) were initially managed conservatively (without surgical intervention), with a success rate of 49%. Only 5 patients (13%) underwent early surgical intervention, which led to resolution of the effusion in 3 of 5 patients (60%). One patient with chylothorax after pericardiectomy had a recurrence after pleurectomy and talc pleurodesis, then underwent a LeVeen shunt placement, which was also ineffective, and was eventually treated with prolonged drainage and dietary measures (total parenteral nutrition) with eventual resolution © 2010 Lippincott Williams & Wilkins
TABLE 2. Outcomes associated with surgical interventions for traumatic chylothorax (n ⫽ 25) Mode of management Talc pleurodesis alone Mechanical and talc pleurodesis Thoracic duct ligation alone Thoracic duct ligation and mechanical pleurodesis Thoracic duct ligation and talc pleurodesis Thoracic duct ligation and pleurectomy Overall
No. patients (%)
Success rate (%)
1 (4) 1 (4)
100 0
5 (20) 4 (16)
100 75
12 (48)
100
2 (8)
100
25 (100)
92
of the effusion. The other patient with unsuccessful surgical result was hospitalized on several occasions and eventually died from complications associated with her heart transplant. During the clinical course, dietary measures were used for 35 of 40 patients (88%). Thoracic duct ligation was used in 23 of 40 patients (58%) and pleurodesis or pleurectomy in 20 of 40 patients (50%; Table 2). Reaccumulation or persistence of chylothorax occurred in 2 of 20 (10%) pleurodesis/pleurectomy patients: 1 after combination of talc and mechanical pleurodesis and another after thoracic duct ligation and mechanical pleurodesis. Overall, 25 patients (63%) with traumatic chylothorax underwent a surgical intervention for treatment of their chylothorax. Lymphangiography (n ⫽ 6) data were available for 6 patients (15%) with traumatic causes. Obstruction at the level of the subclavian or internal jugular vein was identified in 2 patients, infradiaphragmatic obstruction of unclear etiology in 2 patients, and a thoracic duct leak was identified in 1 patient. In the remaining patient, lymphangiogram did not reveal any abnormalities. Subsequent management of chylothorax did not seem to be affected by the results of these studies. Only 2 of these patients underwent an intervention on the thoracic duct after lymphangiography: 1 patient underwent a thoracic duct ligation just above the diaphragm at our institution and another patient underwent a surgical procedure of unclear nature at a different medical center. Nontraumatic Chylothorax The types of initial treatment and respective outcomes are summarized in Table 3. Most patients (21 of 34 patients, 62%) were initially treated with serial thoracenteses (at least 3 thoracentesis after the diagnosis of chylothorax established), with a success rate of 24% (5 patients). Eight patients underwent early surgical intervention (24%). Nonthoracic maneuvers were used in some patients; 2 patients with cirrhosis underwent liver transplantation with prompt resolution of chylothorax and chylous ascites. Two other patients with cirrhosis expired before transplant: 1 had resolution of the chylothorax after talc pleurodesis (but persistence of chylous ascites) and another had persistence of his chylothorax despite a transjugular intrahepatic portosystemic shunt. One patient with bilateral subclavian thromboses (secondary to thoracic outlet syndrome) had bilateral vascular stents placed without effect on the chylothorax. During the clinical course, dietary measures were used in only 5 of 34 patients (15%), thoracic duct ligation was used in 13 patients (38%), and pleurodesis or pleurectomy were in 17
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TABLE 3. Initial interventions and associated outcomes for patients with nontraumatic chylothorax Type of initial treatment Observation onlya Thoracentesis Chest tube drainage Pleurodesis Pleurodesis and thoracic duct ligation LeVeen shunt Overall
No. patients (%)
Success rate (%)
3 (9) 21 (62) 2 (6) 3 (9) 4 (12)
33 24 0 33 50
1 (3) 34 (100)
0 27
a One of these 3 patients received chemotherapy for the treatment of underlying lymphoma and had resolution of chylothorax.
patients (50%; Table 4). Overall, 19 patients with nontraumatic chylothorax underwent a surgical intervention for treatment of their chylothorax (56%). Reaccumulation or persistence of chylothorax occurred in 17 patients (50%). Of these, 6 died (3 from malignancy, 1 from respiratory failure, and 1 from complications of cirrhosis and for unclear reasons). Of those alive, 2 had complete resolution after liver transplant, 1 after chemotherapy for lymphoma. Of the remaining patients, 3 had stable effusions without clinical consequences, 1 had a LeVeen shunt, which was unsuccessful, and 1 had bilateral subclavian stents to relieve obstruction, also unsuccessful. Follow-up data were not available for the other 5 patients. Lymphangiography (10 patient) and lymphoscintigraphy (1 patient) data were available for 11 patients (32%) with nontraumatic chylothorax. Findings included obstruction of the thoracic duct at midcourse in 2 patients and obstruction at the junction of the thoracic duct with the central venous system in 2 other patients. The study was inadequate for interpretation in 1 patient, and another had an anaphylactic reaction necessitating a premature termination of the study. In the remaining 4 patients, lymphangiogram
TABLE 4. Outcomes associated with surgical interventions for nontraumatic chylothorax (n ⫽ 19) Mode of management Talc pleurodesis alone Thoracic duct ligation alonea Thoracic duct ligation and mechanical pleurodesis Thoracic duct ligation and talc pleurodesis Thoracic duct ligation with mechanical and talc pleurodesis Thoracic duct ligation and pleurectomy LeVeen shunt Overall
No. patients (%)
Success rate (%)
5 (26) 1 (5) 2 (11)
80 0 50
8 (42)
88
1 (5)
0%
1 (5)
100
1 (5) 19 (100)
0 68
a The patient who underwent thoracic duct ligation alone eventually underwent palliative placement of an indwelling pleural drainage catheter for malignant pleural effusion with metastatic adenocarcinoma.
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showed no obvious abnormalities. Lymphoscintigraphy was used in 1 patient and showed a blockage in the ilioinguinal region (patient with lymphatic dysplasia syndrome). None of these studies seemed to directly influence the subsequent management of the chylothorax. Comparison of Traumatic and Nontraumatic Groups For the entire cohort of patients, a surgical procedure was eventually performed in 44 of 74 patients (59%), with a rate that was similar between traumatic and nontraumatic groups (62% and 56%, respectively). The rate of resolution with initial management measures was significantly worse for nontraumatic chylothorax than for traumatic group (27% versus 50%, P ⫽ 0.048). Even after additional therapeutic maneuvers, chylous effusion recurred or persisted more commonly in nontraumatic chylothorax when compared with the traumatic group (50% versus 13%, respectively, P ⬍ 0.001).
DISCUSSION In this retrospective study of 74 cases of chylothorax of varying etiology, initial treatment approaches were commonly unsuccessful, and the majority of patients eventually underwent surgical interventions. Even after surgical maneuvers, one third of patients with nontraumatic chylothorax failed to achieve resolution of their pleural effusion. Chylothorax is an uncommon form of pleural effusion and a rare complication of thoracic surgical procedures (⬃0.5% of the cases).2,5 The diagnosis of chylothorax is often delayed because of its rare occurrence and variable gross appearance and biochemical characteristics. It is, however, crucial to recognize the chylous nature of a pleural effusion to appropriately search for the underlying cause and guide management. The diagnosis of chylothorax has traditionally relied on detection of an elevated triglyceride level (⬎110 mg/dL) in the pleural fluid. However, some chylous pleural effusions may exhibit a low triglyceride level, for example, in fasting patients, and lipoprotein electrophoresis may need to be performed for the detection of chylomicrons in the pleural fluid.6,7,15 Once the diagnosis of chylothorax is established, decisions regarding additional diagnostic evaluation and management are difficult to establish because no evidence-based guidelines addressing these issues exist. Indeed, although various approaches to treatment have been described, little evidence supports one approach over another. Traumatic Chylothorax In cases of traumatic chylothorax, most authors have recommended an initial attempt at a conservative approach consisting of chest tube drainage and dietary measures (low-fat diet with medium chain triglyceride supplementation or total parenteral nutrition) before considering surgical intervention.1,8 –10,13,14 In our series, most patients with postsurgical chylothoraces were initially managed conservatively, with a success rate of 49%. Conservative measures have been shown to be less effective in high-volume drainage (⬎1000 mL/d for ⱖ7 days) and after esophageal surgeries.5 Three of 5 patients with chylothorax after esophageal surgery in our study failed conservative therapeutic measures. We did not find the outcome of surgical approaches in patients with high-output drainage to be worse, but the number of patients with relevant data available was limited (20 patients). The initial approach chosen, whether surgical or conservative, resulted in resolution of the chylothorax in half of the patients. There was no significant difference in rates of success Volume 339, Number 4, April 2010
Management of Chylothorax
whether the initial mode of management was medical or surgical although the analysis was limited by the modest number of subjects and the retrospective nature of the study. Based on available data, it seems reasonable to recommend an initial trial of medical measures for several days, before advancing to more invasive options. Eventual resolution can be achieved in most patients with traumatic chylothorax with treatment measure that may include surgical maneuvers in more than one half of these patients. Nontraumatic Chylothorax Optimal management of nontraumatic chylothorax is even more difficult to determine, because there exists a wide spectrum of medical disorders associated with the development of chylothorax. Although treatment of the underlying disease is often recommended as the definitive treatment of nontraumatic chylothorax, the effectiveness of this approach is unclear and may vary widely depending on the underlying disease and the clinical context. Our data suggest that medical management of nontraumatic chylothorax leads to resolution in only a minority of cases. The majority (62%) of our patients with nontraumatic chylothorax were initially treated with periodic thoracenteses, with a resolution rate of only 19%. As mentioned above, the rate of success with initial management measures was significantly worse for the nontraumatic group compared with that for the traumatic group. Furthermore, chylous effusions recurred or persisted more commonly in the nontraumatic group compared with the traumatic group. This difference may be partly explained by the reversible nature of chyle leak induced by surgical trauma in contrast to chronic leak resulting from various medical disorders. Combined Traumatic and Nontraumatic Groups Lymphangiographic or lymphoscintigraphy data were performed in a minority of our patients and did not seem to guide subsequent management. Based on our data and previous studies, the value of these imaging studies seems uncertain in the management of chylothorax. However, other authors have suggested otherwise, particularly in the context of performing percutaneous thoracic duct maneuvers.13,16 None of the patients in our study underwent percutaneous or surgical treatment directed specifically at the site of thoracic duct leak or obstruction.13,17,18 Because of uncommon occurrence of chylothorax, there are no comparative treatment trials available in the literature, and available data are derived mostly from retrospective case series. The management of postsurgical chylothoraces has been studied more extensively than nontraumatic ones. Prolonged drainage of chylous effusions should be avoided as they may adversely affect outcome, predisposing patients to malnutrition, poor wound healing, and infections. One of the largest studies on traumatic chylothorax described 47 patients experiencing chylothorax after thoracic surgery. Conservative management (chest tube drainage and dietary measures) was effective in 13 patients, but reoperation was necessary in the remaining 34 cases. In this study, esophageal surgeries and a drainage ⬎1000 mL for 7 days or more were predictive of the need for surgical reintervention.8 Because the mortality rate of untreated chylothoraces seems to be particularly high in patients who have undergone esophageal operations, early reoperation has been recommended for these patients.19 –21 Although no guidelines exist and surgical practices vary widely, the general consensus suggests an initial conservative approach followed by surgical management if needed.1,8,9,22 One retro© 2010 Lippincott Williams & Wilkins
spective study including 29 patients, mostly postsurgical with minor trauma to the thoracic duct undetected during surgery, reported a 79% success rate with conservative measures.23 Published studies on nontraumatic chylothorax have mainly focused on chylothorax associated with malignancies. In such cases, radiotherapy with or without chemotherapy, followed by talc pleurodesis, if needed, seems to have been a relatively successful treatment approach.24,25 Available literature on the management of chylous effusions secondary to other medical diseases is relatively scarce.26,27 Our study suggests that nontraumatic chylothoraces generally tend to be treated less aggressively than their traumatic counterparts in the initial management, with an overall low rate of success. Treatment of the underlying cause seems reasonable whenever possible, but a substantial portion of patients with nontraumatic chylothorax are left with persistent effusion. Despite incorporation of surgical maneuvers in their management, nearly one third of patients with nontraumatic chylothorax may fail to achieve resolution of their chylothorax.
CONCLUSIONS Chylothorax is an uncommon disorder that results from traumatic and nontraumatic causes and is managed with various treatment approaches. Nonsurgical approaches may lead to resolution of the chylothorax in nearly one half of patients with traumatic chylothorax but in only a minority of those with nontraumatic chylothorax. The majority of patients with nontraumatic chylothorax will eventually require surgical maneuvers, but one third of such patients fail to resolve their chylothorax. REFERENCES 1. Nair SK, Petko M, Hayward MP. Aetiology and management of chylothorax in adults. Eur J Cardiothorac Surg 2007;32:362–9. 2. Platis IE, Nwogu CE. Chylothorax. Thorac Surg Clin 2006;16: 209 –14. 3. Skandalakis JE, Skandalakis LJ, Skandalakis PN. Anatomy of the lymphatics. Surg Oncol Clin North Am 2007;16:1–16. 4. McGrath EE, Blades Z, Anderson PB. Chylothorax: aetiology, diagnosis and therapeutic options. Respir Med In press. 5. Cerfolio RJ. Chylothorax after esophagogastrectomy. Thorac Surg Clin 2006;16:49 –52. 6. Agrawal V, Doelken P, Sahn SA. Pleural fluid analysis in chylous pleural effusion. Chest 2008;133:1436 – 41. 7. Maldonado F, Hawkins FJ, Daniels CE, et al. Pleural fluid characteristics of chylothorax. Mayo Clin Proc 2009;84:129 –33. 8. Cerfolio RJ, Allen MS, Deschamps C, et al. Postoperative chylothorax. J Thorac Cardiovasc Surg 1996;112:1361–5; discussion 1365– 6. 9. Panthongviriyakul C, Bines JE. Post-operative chylothorax in children: an evidence-based management algorithm. J Paediatr Child Health 2008;44:716 –21. 10. Scorza LB, Goldstein BJ, Mahraj RP. Modern management of chylous leak following head and neck surgery: a discussion of percutaneous lymphangiography-guided cannulation and embolization of the thoracic duct. Otolaryngol Clin North Am 2008;41:1231– 40, xi. 11. Smoke A, Delegge MH. Chyle leaks: consensus on management? Nutr Clin Pract 2008;23:529 –32. 12. Epaud R, Dubern B, Larroquet M, et al. Therapeutic strategies for idiopathic chylothorax. J Pediatr Surg. 2008;43:461–5. 13. Boffa DJ, Sands MJ, Rice TW, et al. A critical evaluation of a
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percutaneous diagnostic and treatment strategy for chylothorax after thoracic surgery. Eur J Cardiothorac Surg 2008;33:435–9.
thorax complicating transhiatal esophagectomy without thoracotomy. Surgery 1988;104:720 – 6.
14. Chan EH, Russell JL, Williams WG, et al. Postoperative chylothorax after cardiothoracic surgery in children. Ann Thorac Surg 2005;80: 1864 –70.
21. Lagarde SM, Omloo JM, de Jong K, et al. Incidence and management of chyle leakage after esophagectomy. Ann Thorac Surg 2005; 80:449 –54.
15. Staats BA, Ellefson RD, Budahn LL, et al. The lipoprotein profile of chylous and nonchylous pleural effusions. Mayo Clin Proc 1980;55: 700 – 4.
22. Fahimi H, Casselman FP, Mariani MA, et al. Current management of postoperative chylothorax. Ann Thorac Surg 2001;71:448 –50; discussion 450 –1.
16. Cope C, Kaiser LR. Management of unremitting chylothorax by percutaneous embolization and blockage of retroperitoneal lymphatic vessels in 42 patients. J Vasc Interv Radiol 2002;13: 1139 – 48.
23. Marts BC, Naunheim KS, Fiore AC, et al. Conservative versus surgical management of chylothorax. Am J Surg 1992;164:532– 4; discussion 534 –5.
17. Choo JC, Foley PT, Lyon SM. Percutaneous management of highoutput chylothorax: case reviews. Cardiovasc Intervent Radiol 2009; 32:828 –32. 18. 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. 19. Bolger C, Walsh TN, Tanner WA, et al. Chylothorax after oesophagectomy. Br J Surg 1991;78:587– 8. 20. Orringer MB, Bluett M, Deeb GM. Aggressive treatment of chylo-
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24. Mares DC, Mathur PN. Medical thoracoscopic talc pleurodesis for chylothorax due to lymphoma: a case series. Chest 1998;114: 731–5. 25. Weissberg D, Ben-Zeev I. Talc pleurodesis. Experience with 360 patients. J Thorac Cardiovasc Surg 1993;106:689 –95. 26. Browse NL, Allen DR, Wilson NM. Management of chylothorax. Br J Surg 1997;84:1711– 6. 27. Wurnig PN, Hollaus PH, Ohtsuka T, et al. Thoracoscopic direct clipping of the thoracic duct for chylopericardium and chylothorax. Ann Thorac Surg 2000;70:1662–5.
Volume 339, Number 4, April 2010
Medical and Surgical Management of Chylothorax and Associated Outcomes Fabien Maldonado, MD, Rodrigo Cartin-Ceba, MD, Finn J. Hawkins, MBBCh and Jay H. Ryu, MD
Abstract: Chylothorax is an uncommon form of pleural effusion that can be associated with traumatic and nontraumatic causes. Optimal management and outcome for patients with chylothorax remain unclear. This retrospective single-center study assessed the modes of management for chylothorax in 74 adult patients (ⱖ18 years old) and associated outcomes. The role of lymphangiographic imaging was also evaluated. Initial treatment approach was nonsurgical in 57 patients (77%) but a surgical procedure (pleurodesis, thoracic duct ligation, and/or surgical repair) was eventually performed in 44 patients (59%). The rate of resolution with initial treatment measures was significantly worse for patients with nontraumatic chylothorax compared with those with traumatic causes (27% versus 50%, P ⫽ 0.048). Even after additional therapeutic maneuvers including surgery, chylous effusion recurred more commonly in nontraumatic chylothorax when compared with the traumatic group (50% versus 13%, respectively, P ⬍ 0.001). Lymphatic imaging did not seem to materially influence management. Nonsurgical approaches may lead to resolution of the chylothorax in nearly one half of patients with traumatic chylothorax but in only a minority of those with nontraumatic chylothorax. The majority of patients with nontraumatic chylothorax will eventually require surgical maneuvers, but one third of such patients still fail to resolve their chylothorax. Key Indexing Terms: Chylothorax; Pleural effusion; Pleurodesis; Thoracic duct ligation. [Am J Med Sci 2010;339(4):314–318.]
C
hylothorax is an uncommon type of pleural effusion defined by the presence of chyle in the pleural space.1,2 Chyle is a complex fluid of intestinal origin and composed of lipids, electrolytes, proteins, and lymphocytes (primarily T lymphocytes). The cisterna chyli, located anterior to the first or second lumbar vertebrae, mark the beginning of the thoracic duct, the main lymphatic vessel responsible for the transport of chyle from the abdominal cavity to the central venous system. The thoracic duct enters the thoracic cavity through the aortic hiatus, runs along the right of the thoracic spine, posterior to the esophagus, and crosses the midline between the fourth and sixth thoracic vertebrae level before entering the left internal jugular or subclavian vein in the superior mediastinum. Although considerable variations exist, this anatomy explains the preferential lateralization of chylous effusions depending on the level of thoracic duct injury or obstruction.1,3,4
Division of Pulmonary and Critical Care Medicine (FM, RC-C, JHR), Mayo Clinic, Rochester, Minnesota; and Mayo Graduate School of Medicine (FM, RC-C, FJH), Mayo Clinic, Rochester, Minnesota. Submitted October 2, 2009; accepted in revised form November 25, 2009. This study was supported by Mayo Clinic Foundation. The authors report no potential conflict of interest. Correspondence: Fabien Maldonado, MD, Division of Pulmonary and Critical Care Medicine, Gonda 18 South, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905 (E-mail: [email protected]).
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The diagnosis of chylothorax is sometimes straightforward, especially after chest trauma or surgical procedures, for example, esophagectomy, well known to be associated with the development of chylothorax.5 It can be more difficult to recognize in nontraumatic contexts. A delay in diagnosis can occur as the gross appearance and even biochemical properties of chylous pleural fluid may be altered by multiple factors, such as the nutritional status of the patient and concomitant illnesses.6,7 Prolonged chylous fluid drainage may result in malnutrition, immunocompromised state, and severe electrolyte abnormalities, potentially contributing to increased morbidity and mortality.1,2 Differing management strategies have been described over the years. Although attempts at a more systematic approach to treating chylothorax have been presented, the evidence for such recommendations remains scarce, including the absence of controlled clinical trials, largely because of the uncommon occurrence of this disorder.1,8 –14 We recently published data on the biochemical characteristics of chylous pleural effusions based on a retrospective review of 74 cases encountered over a 10-year period at our tertiary referral medical center.7 In this study, we report on the management aspects of these patients with respect to types of treatment, complications, and associated outcome. We also assess the clinical impact of lymphangiographic or lymphoscintigraphic data.
METHODS Study Subjects We conducted a computer-assisted search of electronic medical records at the Mayo Clinic, Rochester, MN, from January 1, 1997, through December 31, 2006, and identified a cohort of 74 adult patients (ⱖ18 years old) diagnosed with chylothorax as evidenced by the presence of chylomicrons in the pleural fluid. The biochemical characteristics (including triglyceride, lactate dehydrogenase, protein, and cholesterol levels) of the pleural fluid have been presented in a previous report.7 Clinical Data Medical records were carefully examined and the following data were retrieved: age, sex, cause of chylothorax (as assigned by consensus of 2 of the authors, FM and JHR), amount of pleural fluid drainage per day, initial treatment and response, other treatments including type of surgical treatment when applicable, time to resolution of chylothorax, time to recurrence, complications, and mortality. We also reviewed lymphangiography and lymphoscintigraphy data, when available, and evaluated impact on management and outcome. Success in the management of chylothorax was defined by resolution of the pleural effusion without documented recurrence in the follow-up period.
The American Journal of the Medical Sciences • Volume 339, Number 4, April 2010
Management of Chylothorax
TABLE 1. Initial interventions and associated outcomes for patients with traumatic chylothorax (n ⫽ 40) Mode of management Dietary measures onlya Thoracentesis only Dietary measures and thoracentesis Chest tube drainage alone Dietary measures and chest tube drainage Dietary measures and surgical pleurodesis Thoracic duct ligation Surgical pleurodesis and thoracic duct ligation Overall a
No. patients (%)
Success rate (%)
4 (10) 3 (8) 2 (5)
50 66 50
3 (8) 23 (58)
67 43
1 (3)
100
1 (3) 3 (8)
100 33
40 (100)
50
One of these patients also received octreotide therapy.
Statistical Analyses Continuous data are presented as median and range, when appropriate, and percentages for categorical variables. Continuous data were analyzed using Wilcoxon rank-sum test and 2 or Fisher exact test for categorical variables as appropriate. In all cases, a P-value ⬍0.05 was considered significant (2-tailed).
RESULTS There were 37 men (50%) and 37 women (50%). The median age was 61.5 years (range, 20 –93 years). Pleural effusion was unilateral in 58 patients (78%) and involved the right hemithorax in 39 patients (67%) and left hemithorax in 19 patients (33%). Pleural effusion was bilateral in the remaining 16 patients (22%). Of the 74 cases of chylothorax analyzed, 40 (54%) were associated with a traumatic (surgery or invasive procedure) cause and 34 (46%) were nontraumatic or idiopathic in origin. The traumatic group included 39 patients who developed chylothorax as a result of surgery (mostly esophageal, pulmonary, or cardiac); 1 remaining patient had thrombosis of a central vein after central venous cannulation. Nontraumatic causes included 9 lymphoproliferative disorders, 5 portal hypertension from cirrhosis or pancreatic cancer, 3 radiation-related injuries, 3 primary lymphatic disorders, 3 solid tumors, 2 thoracic duct obstruction from subclavian thromboses (idiopathic and secondary to thoracic outlet syndrome, respectively), and 1 case each of lymphangioleiomyomatosis and amyloidosis. No cause was identifiable in 7 remaining cases. Traumatic Chylothorax The types of initial treatment and respective outcomes are summarized in Table 1. Most patients (35 of 40, 88%) were initially managed conservatively (without surgical intervention), with a success rate of 49%. Only 5 patients (13%) underwent early surgical intervention, which led to resolution of the effusion in 3 of 5 patients (60%). One patient with chylothorax after pericardiectomy had a recurrence after pleurectomy and talc pleurodesis, then underwent a LeVeen shunt placement, which was also ineffective, and was eventually treated with prolonged drainage and dietary measures (total parenteral nutrition) with eventual resolution © 2010 Lippincott Williams & Wilkins
TABLE 2. Outcomes associated with surgical interventions for traumatic chylothorax (n ⫽ 25) Mode of management Talc pleurodesis alone Mechanical and talc pleurodesis Thoracic duct ligation alone Thoracic duct ligation and mechanical pleurodesis Thoracic duct ligation and talc pleurodesis Thoracic duct ligation and pleurectomy Overall
No. patients (%)
Success rate (%)
1 (4) 1 (4)
100 0
5 (20) 4 (16)
100 75
12 (48)
100
2 (8)
100
25 (100)
92
of the effusion. The other patient with unsuccessful surgical result was hospitalized on several occasions and eventually died from complications associated with her heart transplant. During the clinical course, dietary measures were used for 35 of 40 patients (88%). Thoracic duct ligation was used in 23 of 40 patients (58%) and pleurodesis or pleurectomy in 20 of 40 patients (50%; Table 2). Reaccumulation or persistence of chylothorax occurred in 2 of 20 (10%) pleurodesis/pleurectomy patients: 1 after combination of talc and mechanical pleurodesis and another after thoracic duct ligation and mechanical pleurodesis. Overall, 25 patients (63%) with traumatic chylothorax underwent a surgical intervention for treatment of their chylothorax. Lymphangiography (n ⫽ 6) data were available for 6 patients (15%) with traumatic causes. Obstruction at the level of the subclavian or internal jugular vein was identified in 2 patients, infradiaphragmatic obstruction of unclear etiology in 2 patients, and a thoracic duct leak was identified in 1 patient. In the remaining patient, lymphangiogram did not reveal any abnormalities. Subsequent management of chylothorax did not seem to be affected by the results of these studies. Only 2 of these patients underwent an intervention on the thoracic duct after lymphangiography: 1 patient underwent a thoracic duct ligation just above the diaphragm at our institution and another patient underwent a surgical procedure of unclear nature at a different medical center. Nontraumatic Chylothorax The types of initial treatment and respective outcomes are summarized in Table 3. Most patients (21 of 34 patients, 62%) were initially treated with serial thoracenteses (at least 3 thoracentesis after the diagnosis of chylothorax established), with a success rate of 24% (5 patients). Eight patients underwent early surgical intervention (24%). Nonthoracic maneuvers were used in some patients; 2 patients with cirrhosis underwent liver transplantation with prompt resolution of chylothorax and chylous ascites. Two other patients with cirrhosis expired before transplant: 1 had resolution of the chylothorax after talc pleurodesis (but persistence of chylous ascites) and another had persistence of his chylothorax despite a transjugular intrahepatic portosystemic shunt. One patient with bilateral subclavian thromboses (secondary to thoracic outlet syndrome) had bilateral vascular stents placed without effect on the chylothorax. During the clinical course, dietary measures were used in only 5 of 34 patients (15%), thoracic duct ligation was used in 13 patients (38%), and pleurodesis or pleurectomy were in 17
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TABLE 3. Initial interventions and associated outcomes for patients with nontraumatic chylothorax Type of initial treatment Observation onlya Thoracentesis Chest tube drainage Pleurodesis Pleurodesis and thoracic duct ligation LeVeen shunt Overall
No. patients (%)
Success rate (%)
3 (9) 21 (62) 2 (6) 3 (9) 4 (12)
33 24 0 33 50
1 (3) 34 (100)
0 27
a One of these 3 patients received chemotherapy for the treatment of underlying lymphoma and had resolution of chylothorax.
patients (50%; Table 4). Overall, 19 patients with nontraumatic chylothorax underwent a surgical intervention for treatment of their chylothorax (56%). Reaccumulation or persistence of chylothorax occurred in 17 patients (50%). Of these, 6 died (3 from malignancy, 1 from respiratory failure, and 1 from complications of cirrhosis and for unclear reasons). Of those alive, 2 had complete resolution after liver transplant, 1 after chemotherapy for lymphoma. Of the remaining patients, 3 had stable effusions without clinical consequences, 1 had a LeVeen shunt, which was unsuccessful, and 1 had bilateral subclavian stents to relieve obstruction, also unsuccessful. Follow-up data were not available for the other 5 patients. Lymphangiography (10 patient) and lymphoscintigraphy (1 patient) data were available for 11 patients (32%) with nontraumatic chylothorax. Findings included obstruction of the thoracic duct at midcourse in 2 patients and obstruction at the junction of the thoracic duct with the central venous system in 2 other patients. The study was inadequate for interpretation in 1 patient, and another had an anaphylactic reaction necessitating a premature termination of the study. In the remaining 4 patients, lymphangiogram
TABLE 4. Outcomes associated with surgical interventions for nontraumatic chylothorax (n ⫽ 19) Mode of management Talc pleurodesis alone Thoracic duct ligation alonea Thoracic duct ligation and mechanical pleurodesis Thoracic duct ligation and talc pleurodesis Thoracic duct ligation with mechanical and talc pleurodesis Thoracic duct ligation and pleurectomy LeVeen shunt Overall
No. patients (%)
Success rate (%)
5 (26) 1 (5) 2 (11)
80 0 50
8 (42)
88
1 (5)
0%
1 (5)
100
1 (5) 19 (100)
0 68
a The patient who underwent thoracic duct ligation alone eventually underwent palliative placement of an indwelling pleural drainage catheter for malignant pleural effusion with metastatic adenocarcinoma.
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showed no obvious abnormalities. Lymphoscintigraphy was used in 1 patient and showed a blockage in the ilioinguinal region (patient with lymphatic dysplasia syndrome). None of these studies seemed to directly influence the subsequent management of the chylothorax. Comparison of Traumatic and Nontraumatic Groups For the entire cohort of patients, a surgical procedure was eventually performed in 44 of 74 patients (59%), with a rate that was similar between traumatic and nontraumatic groups (62% and 56%, respectively). The rate of resolution with initial management measures was significantly worse for nontraumatic chylothorax than for traumatic group (27% versus 50%, P ⫽ 0.048). Even after additional therapeutic maneuvers, chylous effusion recurred or persisted more commonly in nontraumatic chylothorax when compared with the traumatic group (50% versus 13%, respectively, P ⬍ 0.001).
DISCUSSION In this retrospective study of 74 cases of chylothorax of varying etiology, initial treatment approaches were commonly unsuccessful, and the majority of patients eventually underwent surgical interventions. Even after surgical maneuvers, one third of patients with nontraumatic chylothorax failed to achieve resolution of their pleural effusion. Chylothorax is an uncommon form of pleural effusion and a rare complication of thoracic surgical procedures (⬃0.5% of the cases).2,5 The diagnosis of chylothorax is often delayed because of its rare occurrence and variable gross appearance and biochemical characteristics. It is, however, crucial to recognize the chylous nature of a pleural effusion to appropriately search for the underlying cause and guide management. The diagnosis of chylothorax has traditionally relied on detection of an elevated triglyceride level (⬎110 mg/dL) in the pleural fluid. However, some chylous pleural effusions may exhibit a low triglyceride level, for example, in fasting patients, and lipoprotein electrophoresis may need to be performed for the detection of chylomicrons in the pleural fluid.6,7,15 Once the diagnosis of chylothorax is established, decisions regarding additional diagnostic evaluation and management are difficult to establish because no evidence-based guidelines addressing these issues exist. Indeed, although various approaches to treatment have been described, little evidence supports one approach over another. Traumatic Chylothorax In cases of traumatic chylothorax, most authors have recommended an initial attempt at a conservative approach consisting of chest tube drainage and dietary measures (low-fat diet with medium chain triglyceride supplementation or total parenteral nutrition) before considering surgical intervention.1,8 –10,13,14 In our series, most patients with postsurgical chylothoraces were initially managed conservatively, with a success rate of 49%. Conservative measures have been shown to be less effective in high-volume drainage (⬎1000 mL/d for ⱖ7 days) and after esophageal surgeries.5 Three of 5 patients with chylothorax after esophageal surgery in our study failed conservative therapeutic measures. We did not find the outcome of surgical approaches in patients with high-output drainage to be worse, but the number of patients with relevant data available was limited (20 patients). The initial approach chosen, whether surgical or conservative, resulted in resolution of the chylothorax in half of the patients. There was no significant difference in rates of success Volume 339, Number 4, April 2010
Management of Chylothorax
whether the initial mode of management was medical or surgical although the analysis was limited by the modest number of subjects and the retrospective nature of the study. Based on available data, it seems reasonable to recommend an initial trial of medical measures for several days, before advancing to more invasive options. Eventual resolution can be achieved in most patients with traumatic chylothorax with treatment measure that may include surgical maneuvers in more than one half of these patients. Nontraumatic Chylothorax Optimal management of nontraumatic chylothorax is even more difficult to determine, because there exists a wide spectrum of medical disorders associated with the development of chylothorax. Although treatment of the underlying disease is often recommended as the definitive treatment of nontraumatic chylothorax, the effectiveness of this approach is unclear and may vary widely depending on the underlying disease and the clinical context. Our data suggest that medical management of nontraumatic chylothorax leads to resolution in only a minority of cases. The majority (62%) of our patients with nontraumatic chylothorax were initially treated with periodic thoracenteses, with a resolution rate of only 19%. As mentioned above, the rate of success with initial management measures was significantly worse for the nontraumatic group compared with that for the traumatic group. Furthermore, chylous effusions recurred or persisted more commonly in the nontraumatic group compared with the traumatic group. This difference may be partly explained by the reversible nature of chyle leak induced by surgical trauma in contrast to chronic leak resulting from various medical disorders. Combined Traumatic and Nontraumatic Groups Lymphangiographic or lymphoscintigraphy data were performed in a minority of our patients and did not seem to guide subsequent management. Based on our data and previous studies, the value of these imaging studies seems uncertain in the management of chylothorax. However, other authors have suggested otherwise, particularly in the context of performing percutaneous thoracic duct maneuvers.13,16 None of the patients in our study underwent percutaneous or surgical treatment directed specifically at the site of thoracic duct leak or obstruction.13,17,18 Because of uncommon occurrence of chylothorax, there are no comparative treatment trials available in the literature, and available data are derived mostly from retrospective case series. The management of postsurgical chylothoraces has been studied more extensively than nontraumatic ones. Prolonged drainage of chylous effusions should be avoided as they may adversely affect outcome, predisposing patients to malnutrition, poor wound healing, and infections. One of the largest studies on traumatic chylothorax described 47 patients experiencing chylothorax after thoracic surgery. Conservative management (chest tube drainage and dietary measures) was effective in 13 patients, but reoperation was necessary in the remaining 34 cases. In this study, esophageal surgeries and a drainage ⬎1000 mL for 7 days or more were predictive of the need for surgical reintervention.8 Because the mortality rate of untreated chylothoraces seems to be particularly high in patients who have undergone esophageal operations, early reoperation has been recommended for these patients.19 –21 Although no guidelines exist and surgical practices vary widely, the general consensus suggests an initial conservative approach followed by surgical management if needed.1,8,9,22 One retro© 2010 Lippincott Williams & Wilkins
spective study including 29 patients, mostly postsurgical with minor trauma to the thoracic duct undetected during surgery, reported a 79% success rate with conservative measures.23 Published studies on nontraumatic chylothorax have mainly focused on chylothorax associated with malignancies. In such cases, radiotherapy with or without chemotherapy, followed by talc pleurodesis, if needed, seems to have been a relatively successful treatment approach.24,25 Available literature on the management of chylous effusions secondary to other medical diseases is relatively scarce.26,27 Our study suggests that nontraumatic chylothoraces generally tend to be treated less aggressively than their traumatic counterparts in the initial management, with an overall low rate of success. Treatment of the underlying cause seems reasonable whenever possible, but a substantial portion of patients with nontraumatic chylothorax are left with persistent effusion. Despite incorporation of surgical maneuvers in their management, nearly one third of patients with nontraumatic chylothorax may fail to achieve resolution of their chylothorax.
CONCLUSIONS Chylothorax is an uncommon disorder that results from traumatic and nontraumatic causes and is managed with various treatment approaches. Nonsurgical approaches may lead to resolution of the chylothorax in nearly one half of patients with traumatic chylothorax but in only a minority of those with nontraumatic chylothorax. The majority of patients with nontraumatic chylothorax will eventually require surgical maneuvers, but one third of such patients fail to resolve their chylothorax. REFERENCES 1. Nair SK, Petko M, Hayward MP. Aetiology and management of chylothorax in adults. Eur J Cardiothorac Surg 2007;32:362–9. 2. Platis IE, Nwogu CE. Chylothorax. Thorac Surg Clin 2006;16: 209 –14. 3. Skandalakis JE, Skandalakis LJ, Skandalakis PN. Anatomy of the lymphatics. Surg Oncol Clin North Am 2007;16:1–16. 4. McGrath EE, Blades Z, Anderson PB. Chylothorax: aetiology, diagnosis and therapeutic options. Respir Med In press. 5. Cerfolio RJ. Chylothorax after esophagogastrectomy. Thorac Surg Clin 2006;16:49 –52. 6. Agrawal V, Doelken P, Sahn SA. Pleural fluid analysis in chylous pleural effusion. Chest 2008;133:1436 – 41. 7. Maldonado F, Hawkins FJ, Daniels CE, et al. Pleural fluid characteristics of chylothorax. Mayo Clin Proc 2009;84:129 –33. 8. Cerfolio RJ, Allen MS, Deschamps C, et al. Postoperative chylothorax. J Thorac Cardiovasc Surg 1996;112:1361–5; discussion 1365– 6. 9. Panthongviriyakul C, Bines JE. Post-operative chylothorax in children: an evidence-based management algorithm. J Paediatr Child Health 2008;44:716 –21. 10. Scorza LB, Goldstein BJ, Mahraj RP. Modern management of chylous leak following head and neck surgery: a discussion of percutaneous lymphangiography-guided cannulation and embolization of the thoracic duct. Otolaryngol Clin North Am 2008;41:1231– 40, xi. 11. Smoke A, Delegge MH. Chyle leaks: consensus on management? Nutr Clin Pract 2008;23:529 –32. 12. Epaud R, Dubern B, Larroquet M, et al. Therapeutic strategies for idiopathic chylothorax. J Pediatr Surg. 2008;43:461–5. 13. Boffa DJ, Sands MJ, Rice TW, et al. A critical evaluation of a
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percutaneous diagnostic and treatment strategy for chylothorax after thoracic surgery. Eur J Cardiothorac Surg 2008;33:435–9.
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14. Chan EH, Russell JL, Williams WG, et al. Postoperative chylothorax after cardiothoracic surgery in children. Ann Thorac Surg 2005;80: 1864 –70.
21. Lagarde SM, Omloo JM, de Jong K, et al. Incidence and management of chyle leakage after esophagectomy. Ann Thorac Surg 2005; 80:449 –54.
15. Staats BA, Ellefson RD, Budahn LL, et al. The lipoprotein profile of chylous and nonchylous pleural effusions. Mayo Clin Proc 1980;55: 700 – 4.
22. Fahimi H, Casselman FP, Mariani MA, et al. Current management of postoperative chylothorax. Ann Thorac Surg 2001;71:448 –50; discussion 450 –1.
16. Cope C, Kaiser LR. Management of unremitting chylothorax by percutaneous embolization and blockage of retroperitoneal lymphatic vessels in 42 patients. J Vasc Interv Radiol 2002;13: 1139 – 48.
23. Marts BC, Naunheim KS, Fiore AC, et al. Conservative versus surgical management of chylothorax. Am J Surg 1992;164:532– 4; discussion 534 –5.
17. Choo JC, Foley PT, Lyon SM. Percutaneous management of highoutput chylothorax: case reviews. Cardiovasc Intervent Radiol 2009; 32:828 –32. 18. 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. 19. Bolger C, Walsh TN, Tanner WA, et al. Chylothorax after oesophagectomy. Br J Surg 1991;78:587– 8. 20. Orringer MB, Bluett M, Deeb GM. Aggressive treatment of chylo-
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24. Mares DC, Mathur PN. Medical thoracoscopic talc pleurodesis for chylothorax due to lymphoma: a case series. Chest 1998;114: 731–5. 25. Weissberg D, Ben-Zeev I. Talc pleurodesis. Experience with 360 patients. J Thorac Cardiovasc Surg 1993;106:689 –95. 26. Browse NL, Allen DR, Wilson NM. Management of chylothorax. Br J Surg 1997;84:1711– 6. 27. Wurnig PN, Hollaus PH, Ohtsuka T, et al. Thoracoscopic direct clipping of the thoracic duct for chylopericardium and chylothorax. Ann Thorac Surg 2000;70:1662–5.
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