MIS Authors: Eli Robins, MD Candidate 2017, Danielle Walsh MD
Overview:
Chylothorax is a condition characterized by chyle accumulation in pleural space. In most instances, this is due to disruption of the thoracic duct or one of its tributaries through surgical manipulation, congenital defects, or malignancy. Without medical intervention, this uncommon type of pleural effusion can lead to significant morbidity and mortality due the loss of essential fats, proteins, electrolytes, and t-lymphocytes. To date, several approaches in management of chylothorax have been proposed, however optimal treatment, namely timing of surgical intervention, remains debated.
Chylothorax affects all patient populations, and has several etiologies. Multiple classification systems exist. However, traditionally, cases of chylothorax are classified as congenital, traumatic, neoplastic, or miscellaneous. 1 Trauma is further subdivided into Iatrogenic and Non Iatrogenic causes. Although prevalence varies with age, trauma and neoplasms account for the majority of cases. 2,3
In neonates, congenital chylothorax is the most common type of pleural effusion affecting 1 in 7000 births. 4 These cases are largely associated with genetic syndromes including, Noonan’s Syndrome, Turners Syndrome, and Trisomy 21. 4 Other causes include congenital defects of the thoracic duct, such as absence or atresia, birthing trauma, and spontaneous idiopathic formation. 5 Congenital chylothorax in neonates is a common manifestation of hydrops fetalis and pulmonary hypoplasia at birth due to impaired venous return and protein loss. 6 For these cases, both antenatal intervention and postnatal care have proven beneficial. 6 In children, congenital chylothorax is also attributed to thoracic duct malformation as well as increased venous pressure following birth. 1 In congenital abnormalities such as pulmonary lymphangiomatosis and lymphangiectasia, patients may present with symptoms several years later. 7 The most common cause of chylothorax in children however, is due to surgical perforation of the thoracic duct or tributary during cardiothoracic surgery. 7
In adults, trauma and malignancy, particularly lymphoma, account for the majority of chylothorax cases. Reports suggest up to 50% of all adult chylothorax patients have cancer, of which 70% are lymphomas. 1,7,8 Iatrogenic etiology in both adolescents and adults occur primarily due to the significant anatomic variation associated with the thoracic duct. 9,10 Incidences of these surgical complications however, are still low with an occurrence rate of 0.5-4% after esophageal and cardiothoracic surgeries. 11,12
Several factors contribute to the management of chylothorax, however care begins in a similar manner regardless of etiology. Once the chylothorax is identified through lipoprotein analysis, management becomes dependent on prior health conditions, localization of the discharge, and rate of chyle loss. Assessing these factors leads to three management options: 1) Treatment of prior health issues such as malignancy or disease, 2) Conservative management, or 3) Procedural intervention. 13 Although several treatment options are available, management strategies are not firmly established, especially concerning timing of aggressive intervention. 2,3,13,14
Diagnosis:
The thoracic duct begins at T12, where it ascends from the cisternae chili in the retroperitoneum. It remains oriented to the right of midline until reaching approximately T6 where it crosses the vertebral body. Superior to T6, the thoracic duct continues its ascent until ultimately anastomosing with the left subclavian vein. Its route gives diagnostic information especially in the case of unilateral perforation. Patients who present with a right-sided pleural effusion generally have a perforation inferior to T6 on the right side, while left-sided effusions are usually indicative of a superior leak. Lesions can also occur bilaterally, which can impact treatment options due the large volume usually associated with it.
Diagnosis of chylothorax is uniform regardless of etiology. Clinically, symptomatic patients present analogous to other pleural effusions with respiratory distress and dyspnea as chief complaints. 15 Assessing trauma can be particularly challenging, as cases may be asymptomatic for up to 10 days post injury. 2 Iatrogenic delay is attributed to limited food intake, inflammation and medication regimen post operatively. If diagnosis is missed or delayed for a considerable length of time, chronic cases can present with significant health concerns including malnutrition, respiratory failure, metabolic acidosis and compromised immunological status. 2 Pleural fluid must be drained and analyzed for a definitive diagnosis.
While there are several methods used for analysis, testing the fluid for the presence of chylomicrons is the gold standard. This is tested though lipoprotein analysis or cytological staining using Sudan III. 3 If lipoprotein analysis is not available, triglyceride and cholesterol levels are analyzed. Pleural contents are considered chylous if triglyceride levels are >110mg/dL and cholesterol levels are <200mg/dL. 16 When triglyceride contents are < 50 mg/dL, there is only a 5% chance the effusion is due to chylothorax. 16 If triglyceride levels are <50 mg/dL, and cholesterol is >200 mg/dL, the effusion is classified as a Pseudochylothorax, which normally indicates a poorly evacuated effusion now enriched in cholesterol. 14 Tuberculosis accounts for over 50% percent of these pleural effusions. 17
Less prevalent are chylothorax cases with triglyceride levels <110 mg/dL. 18 Normally low triglyceride levels in chylothorax are indicative of fasting or malnutrition, which can accompany iatrogenic or chronic cases respectively. 18 While triglyceride levels can be useful in diagnosis, the presence of chylomicrons in pleural fluid always implicates chylothorax making it the best diagnostic tool. If fluid analysis is not available, the most indicative method strengthening clinical suspicion is increased milky output in postprandial pleural drainage. 15
Imaging:
Initial management involves relieving symptoms of dyspnea via thoracocentesis and replacing necessary nutrients. Due to the nutrient content of chyle, careful monitoring is necessary to ensure reverse hypovolemia, immunosuppression, and protein and electrolyte loss do not occur. 3 Treatment once the patient is stabilized involves gauging the rate of chyle loss and area of the perforation or block. 19 For adults with non-traumatic etiologies, a CT scan is advised in order to rule out malignancy. 13 If CT confirms malignancy, treatments such as radiotherapy may alleviate the chylothorax if lymphangiomas are located in the mediastinum.20
There are two methods used to visualize the lymphatic system, however they are rarely performed in the diagnosis of chylothorax. Lymphoscitigraphy confirms chylothorax by using radiolabeled albumin; but poor resolution makes visualizing the site of perforation difficult. 21 Although procedurally more challenging, Lymphangiography is still the gold standard due to its accuracy. 21 Lymphangiography also has the added benefit of causing scerlosant and occlusive effects to the thoracic duct due to the oil based contrast lipiodol. 22,23 While doses >20ml can cause pulmonary arterial embolization, smaller quantities have shown success rates of 50-75% in resolving chylothorax. 24
While prior health conditions and localization of the chyle leak are important, 24-hour chyle volume is the major factor in choosing a treatment plan. Studies have shown a direct correlation of high chyle leakage rate with increased morbidity and mortality. 3
Conservative treatment:
Nonsurgical treatment usually accompanies initial management in an effort to resolve the chylothorax prior to aggressive intervention. In adults, if the effusion output measures <500ml of drainage in the first 24 hours, the chylothorax is classified as low output and conservative management is continued. 2 Studies have shown most cases of low output chylothorax respond well to conservative care. 25
Treatment involves taking steps to reduce the volume of chyle in efforts to alleviate pressure and allow for natural closure of the perforation. 2 Chyle volume can be reduced through the administration of medium chained triglycerides (MCT). Unlike long chained triglycerides, MCT are absorbed directly into the portal system. 13 This therapy has proven to resolve up to 50% of congenital and traumatic chylothorax cases. 26 If chyle flow does not adequately decrease, TPN administration of MCT, while the patient is NPO has proven to further inhibit chyle secretion. 27,28
Pharmacologically Somatostatin has proven very beneficial in decreasing chyle production through inhibition of gastric secretions. 19,29 Studies suggest somatostatin has a success rates around 50% in pediatric cases where dietary restrictions alone fail to inhibit chyle leakage. 30 A synthetic analogue of Somatostatin, Octreotide has been reported as a safe and effective alternative with improved outcomes. 31 Fujita et al demonstrated a 40% increase in the number of patients responsive to conservative therapy when dietary changes and octreotide were combined. Octreotide holds several advantages to somatostatin including a longer half-life, as well as subcutaneous and intravenous administration. 32 The sympathomimetic drug Etilefrine is another pharmacological agent proven effective in limiting chylothorax. 33 Unlike Somatostatin and Octreotide, intravenous administration of Etilefrine induces smooth muscle contraction surrounding the thoracic duct, which limits flow rate. A significant side effect, unfortunately, is tachyphilaxis. 33 Physiologically, if chylothorax is recognized in a ventilated patient postoperatively, the use of positive end expiratory pressure can also help limit thoracic duct leakage. 34
In general, for adults, aggressive management should be considered when chyle leakage is >500ml in the first 24 hours despite fasting, >1000 ml per day for 5 consecutive days, or if chyle leakage has not diminished over the course of 2 weeks. 2 Most series describing chylothorax in children suggest a larger window of 2-4 weeks before operative intervention, due to an 80% success rate using conservative methods. 7,35,36 If the leak rate exceeds 100mg/kg body weight per day however, aggressive therapies should be discussed. 37 Integral factors for choosing the proper aggressive treatment involve age of the patient, current medical conditions, and visualization of the leak site.
Procedural Intervention:
There are several treatment options available if chylothorax ceases to dissolve with conservative management. These involve the use of therapeutic agents, minimally invasive procedures, and open surgery. Although several treatment plans have been proposed, currently there is no consensus outlining when aggressive intervention should be replace conservative care. Several studies maintain timing of aggressive treatment should be case dependent, particularly regarding iatrogenic etiologies and neoplasms. 3,38,39
Procedures:
Percutaneous Thoracic Duct Embolization (TDE):
Percutaneous Thoracic duct embolization (TDE) is a rare, yet established, alternative to Thoracoscopic treatment of chyle leaks. 40 This minimally invasive procedure uses lymphangiography to guide cisterna chili or thoracic duct catheterization and embolization. 19 TDE has reported a 70% success rate, with morbidity less than 2% and no associated mortality. 41,42 Rare associated problems involve embolization of pulmonary arteries from embolitic glue, and chylous ascites. 43,44
The procedure occurs in two phases 1) Visualization and 2) Canulation /Embolization. There are several techniques used to visualize the thoracic duct. Pedal lymphangiography has been the traditional method, however the procedure can be technically challenging. 42 Recently, methods involving ultrasound guided inguinal lymphangiography have proven less technically difficult with decreased procedure time. 40,42 Challenges with this procedure however include finding suitable lymph nodes and access issues in the obese. 42 A retrograde transvenous approach is also possible, but poses a significant challenge due to difficulty locating and seating the catheter in the ostium of the thoracic duct. 42 If lymphatics are too small or fail to opacify, utilization of a needle disruption technique can enhance visualization of upper retroperitoneal lymphatics.44
Procedurally, canulation and embolization are performed using a transabdominal approach from the right internal oblique in order to avoid the aorta. 42 Using a 21 or 22-gauge needle angled at 30°, a “gun site” technique is used to access the thoracic duct. 42 Embolics include dehydrated alcohol, Fibrin glue, Platinum coils, or a combination, which are delivered via microcatheter to seal the leak site. 19
Video-Assisted Thoracoscopic Surgery and Open Thoracotomy:
Video assisted thoracoscopic surgery (VATS) can be used for both thoracic duct ligation and pleurodesis in chylothorax cases. It has proven safer and more cost effective in treating chylothorax in comparison to open thoracotomy. 45 For this reason, some believe VATS may be beneficial in earlier intervention rather than after weeks of conservative care. 3,39,46 This is highlighted in cases of iatrogenic chylothorax post-esophagectomy, where mortality rates reportedly drop 40% when surgical intervention is implemented prior to conservative care. 3,39,46
There are several surgical approaches described for thoracic duct ligation depending on the etiology and location of the leak. Visualization of the thoracic duct during VATS or an open thoracotomy can be enhanced by preoperative ingestion of cream or milk, or injection of 1% Evans Blue dye in the thigh. 47 The procedure is usually performed under single lung ventilation, and traditionally uses 3 ports with positioning depending on the location of the leak. 48,49 In cases involving bilateral chylothorax, surgical intervention is more common due to the larger volume associated. In right-sided cases, the first port is purposed for a 30° scope and is inserted in the right 6th intercostal space. The second port is placed in the right posterior 8th intercostal space for dissection, and the third port is positioned in the anterior-superior axillary line for lung retraction and instrumentation. 3
If the thoracic duct is not visualized after pleural resection, mass ligation has proven useful in managing the problem. 50 Procedurally this involves ligating space in the posterior mediastinum once the aorta, azygos vein, and esophagus have been identified. Due to the vast network of tributaries, overall lymphatic flow will not be affected but the chylothorax should resolve. Traditionally mass ligation occurs supradiaphramically in right pleural space with non-absorbable sutures. 3 The thoracic duct remains on the right side until T-6, therefore ligation at the level of the diaphragm offers the benefit of blocking unrecognized tributaries. 51 In esophageal and cardiothoracic surgeries, ligation can also be used as a prophylactic measure. 52
Repair using Open Thoracotomy is usually a last resort due to the high morbidity (38.8%) and mortality (2.1%) rates. 11
Pleurodesis:
Obliteration of pleural space (Pleurodesis) has proven an effective treatment for chylothorax cases, especially those involving malignancy and select pediatric etiologies. 7,38 Pleurodesis is also a prominent choice when the leak site cannot be identified. 3 Procedurally, it can be performed in a non-operative or operative setting using one of several pharmacological agents. These agents include tetracycline, bleomycin, Talc, or Betadine. For non-operative administration, the patient’s chest tube is used as the delivery point. 53 Operative Pleurodesis involves surgically entering the pleural space followed by direct delivery of a sclerosing agent such as Talc powder. It is usually performed however during VATS, and has shown success rates as high as 95% with very limited morbidity. 54 For neonatal patients, Pleurodesis using OK-425 (Streptococcus Pyogenes) has been implicated in preventing pulmonary hypoplasia and enhancing respiratory function at birth. 55 Contraindications involve individuals with cystic fibrosis due to future transplantation difficulties. Because of the permanence of this procedure, it is typically a secondary option to TED and VATS in healthy individuals.
Pleuroperitoneal shunting:
Pleuroperitoneal shunting is a procedure used for the palliative management of chylothorax in patients who have usually failed pleurodesis, radiation, and chemotherapy. 56 This procedure has also proven safe and effective in treating persistent infantile chylothorax. 57 Pleuroperitoneal shunting is used for all forms of pleural effusion, however in chylothorax it has the added benefit of recycling chyle previously lost in pleural space. The shunt provides a one-way connection from the pleural space to the abdominal peritoneum, and is activated through manual pumping. 58 Complications with shunting include infection and occlusion of the tube. If the patient has had recurrent chylothorax or other forms of pleural effusion, pleural fluid loculation could make shunt placement and drainage difficult. 58
Summary:
Chylothorax is a rare condition that has a variety of etiologies and treatment options. The high success rate accompanying conservative management makes it the preferable initial option for the majority of cases. Fortunately, if symptoms do not resolve, there are several aggressive alternatives available. Both non-operative and operative treatments have significantly reduced the 50% mortality rate associated with chylothorax sixty years ago. While some contend care must be managed on a case-by-case basis, a large control study focusing on optimal timing of surgical intervention could prove to further decrease future morbidity and mortality.
References:
1. Sellke FW, Pedro J, Nido D, Swanson SJ. Sabiston and spencer’s surgery of the chest. Saunders; 2010.
2. Lee H, Gumpeni R, Jain M, Talwar A. Chylothorax: A review of current management strategies. J Resp Dis. 2008;29(8):325-333.
3. Nair SK, Petko M, Hayward MP. Aetiology and management of chylothorax in adults. Eur J Cardiothorac Surg. 2007;32(2):362-369. doi: S1010-7940(07)00418-6 [pii].
4. Downie L, Sasi A, Malhotra A. Congenital chylothorax: Associations and neonatal outcomes. J Paediatr Child Health. 2014;50(3):234-238.
5. Van Aerde J, Campbell AN, Smyth JA, Lloyd D, Bryan MH. Spontaneous chylothorax in newborns. American Journal of Diseases of Children. 1984;138(10):961-964.
6. Dendale J, Comet P, Amram D, Lesbros D. Prenatal diagnosis of chylothorax. Arch Pediatr. 1999;6(8):867-871. doi: S0929693X00884821 [pii].
7. Soto-Martinez M, Massie J. Chylothorax: Diagnosis and management in children. Paediatric respiratory reviews. 2009;10(4):199-207.
8. McWilliams A, Gabbay E. Chylothorax occurring 23 years post‐irradiation: Literature review and management strategies. Respirology. 2000;5(3):301-303.
9. Pernis P. Variations of the thoracic duct. BMC surgery. 1949;26:806-809.
10. Phang K, Bowman M, Phillips A, Windsor J. Review of thoracic duct anatomical variations and clinical implications. Clinical Anatomy. 2014;27(4):637-644.
11. Cerfolio RJ, Allen MS, Deschamps C, Trastek VF, Pairolero PC. Postoperative chylothorax. J Thorac Cardiovasc Surg. 1996;112(5):1361-1366.
12. Chalret du Rieu M, Mabrut J. Management of postoperative chylothorax. Journal of visceral surgery. 2011;148(5):e346-e352.
13. McGrath EE, Blades Z, Anderson PB. Chylothorax: Aetiology, diagnosis and therapeutic options. Respir Med. 2010;104(1):1-8.
14. Hillerdal G. Chylothorax and pseudochylothorax. Eur Respir J. 1997;10(5):1157-1162.
15. Doerr CH, Allen MS, Nichols III FC, Ryu JH. Etiology of chylothorax in 203 patients. . 2005;80(7):867-870.
16. Staats BA, Ellefson RD, Budahn LL, Dines DE, Prakash UB, Offord K. The lipoprotein profile of chylous and nonchylous pleural effusions. Mayo Clin Proc. 1980;55(11):700-704.
17. Garcia-Zamalloa A, Ruiz-Irastorza G, Aguayo FJ, Gurrutxaga N. Pseudochylothorax: Report of 2 cases and review of the literature. Medicine. 1999;78(3):200-207.
18. Maldonado F, Hawkins FJ, Daniels CE, Doerr CH, Decker PA, Ryu JH. Pleural fluid characteristics of chylothorax. . 2009;84(2):129-133.
19. Lyon S, Mott N, Koukounaras J, Shoobridge J, Hudson PV. Role of interventional radiology in the management of chylothorax: A review of the current management of high output chylothorax. Cardiovasc Intervent Radiol. 2013;36(3):599-607.
20. Johnson DW, Klazynski PT, Gordon WH, Russell DA. Mediastinal lymphangioma and chylothorax: The role of radiotherapy. Ann Thorac Surg. 1986;41(3):325-328.
21. Ohtsuka A, Inoue Y, Asano Y, Woodhams R, Shiomi K. Lymphoscintigraphy using dynamic imaging and SPECT/CT in chylothorax. Open Journal of Medical Imaging. 2013;3:86.
22. Kos S, Haueisen H, Lachmund U, Roeren T. Lymphangiography: Forgotten tool or rising star in the diagnosis and therapy of postoperative lymphatic vessel leakage. Cardiovasc Intervent Radiol. 2007;30(5):968-973.
23. Matsumoto T, Yamagami T, Kato T, et al. The effectiveness of lymphangiography as a treatment method for various chyle leakages. . 2014.
24. Guermazi A, Brice P, Hennequin C, Sarfati E. Lymphography: An old technique retains its usefulness 1. Radiographics. 2003;23(6):1541-1558.
25. Choo JC, Foley PT, Lyon SM. Percutaneous management of high-output chylothorax: Case reviews. Cardiovasc Intervent Radiol. 2009;32(4):828-832.
26. Alvarez JF, Kalache KD, Grauel EL. Management of spontaneous congenital chylothorax: Oral medium-chain triglycerides versus total parenteral nutrition. Am J Perinatol. 1999;16(08):0415-0420.
27. Ramos W, Faintuch J. Nutritional management of thoracic duct fistulas. A comparative study of parenteral versus enteral nutrition. JPEN J Parenter Enteral Nutr. 1986;10(5):519-521.
28. Robinson C. The management of chylothorax. Ann Thorac Surg. 1985;39(1):90-95.
29. Ulíbarri JI, Sanz Y, Fuentes C, Mancha A, Aramendia M, Sánchez S. Reduction of lymphorrhagia from ruptured thoracic duct by somatostatin. Lancet. 1990;336(8709):258-258. doi: 10.1016/0140-6736(90)91793-A.
30. Cannizzaro V, Frey B, Bernet-Buettiker V. The role of somatostatin in the treatment of persistent chylothorax in children. Eur J Cardiothorac Surg. 2006;30(1):49-53. doi: S1010-7940(06)00310-1 [pii].
31. Fujita T, Daiko H. Efficacy and predictor of octreotide treatment for postoperative chylothorax after thoracic esophagectomy. World J Surg. 2014:1-7.
32. Markham KM, Glover JL, Welsh RJ, Lucas RJ, Bendick PJ. Octreotide in the treatment of thoracic duct injuries. Am Surg. 2000;66(12):1165-1167.
33. Guillem P, Papachristos I, Peillon C, Triboulet JP. Etilefrine use in the management of post-operative chyle leaks in thoracic surgery. Interact Cardiovasc Thorac Surg. 2004;3(1):156-160. doi: 3/1/156 [pii].
34. Kurtz TW, Hsu CH. Resolution of chylothorax after positive end-expiratory pressure ventilation. Archives of Surgery. 1980;115(1):73-74.
35. Panthongviriyakul C, Bines JE. Post‐operative chylothorax in children: An evidence‐based management algorithm. J Paediatr Child Health. 2008;44(12):716-721.
36. Milonakis M, Chatzis AC, Giannopoulos NM, et al. Etiology and management of chylothorax following pediatric heart surgery. J Card Surg. 2009;24(4):369-373.
37. Marts BC, Naunheim KS, Fiore AC, Pennington DG. Conservative versus surgical management of chylothorax. The American Journal of Surgery. 1992;164(5):532-535. doi: 10.1016/S0002-9610(05)81195-X.
38. Weissberg D, Ben-Zeev I. Talc pleurodesis. experience with 360 patients. J Thorac Cardiovasc Surg. 1993;106(4):689-695.
39. Bolger C, Walsh T, Tanner W, Keeling P, Hennessy T. Chylothorax after oesophagectomy. Br J Surg. 1991;78(5):587-588.
40. Nadolski G, Itkin M. Thoracic duct embolization for the management of chylothoraces. Curr Opin Pulm Med. 2013;19(4):380-386. doi: 10.1097/MCP.0b013e3283610df2 [doi].
41. Marcon F, Irani K, Aquino T, Saunders JK, Gouge TH, Melis M. Percutaneous treatment of thoracic duct injuries. Surg Endosc. 2011;25(9):2844-2848.
42. Mauro MA, Murphy KP, Thomson KR, Venbrux AC, Morgan RA. Image-guided interventions: Expert radiology series. Elsevier Health Sciences; 2013.
43. Gaba RC, Owens CA, Bui JT, Carrillo TC, Knuttinen MG. Chylous ascites: A rare complication of thoracic duct embolization for chylothorax. Cardiovasc Intervent Radiol. 2011;34(2):245-249.
44. Binkert CA, Yucel EK, Davison BD, Sugarbaker DJ, Baum RA. Percutaneous treatment of high-output chylothorax with embolization or needle disruption technique. Journal of vascular and interventional radiology. 2005;16(9):1257-1262.
45. Fahimi H, Casselman FP, Mariani MA, van Boven WJ, Knaepen PJ, van Swieten HA. Current management of postoperative chylothorax. Ann Thorac Surg. 2001;71(2):448-450.
46. Orringer MB, Bluett M, Deeb GM. Aggressive treatment of chylothorax complicating transhiatal esophagectomy without thoracotomy. Surgery. 1988;104(4):720-726.
47. Achildi O, Smith BP, Grewal H. Thoracoscopic ligation of the thoracic duct in a child with spontaneous chylothorax. Journal of Laparoendoscopic & Advanced Surgical Techniques. 2006;16(5):546-549.
48. Graham DD, McGahren ED, Tribble CG, Daniel TM, Rodgers BM. Use of video-assisted thoracic surgery in the treatment of chylothorax. Ann Thorac Surg. 1994;57(6):1507-1512.
49. Kent III RB, Pinson TW. Thoracoscopic ligation of the thoracic duct. Surg Endosc. 1993;7(1):52-53.
50. Stringel G, Teixeira JA. Thoracoscopic ligation of the thoracic duct. JSLS, Journal of the Society of Laparoendoscopic Surgeons. 2000;4(3):239-242.
51. Miyamura H, Watanabe H, Eguchi S, Suzuki T. Ligation of the thoracic duct through transabdominal phrenotomy for chylothorax after heart operations. J Thorac Cardiovasc Surg. 1994;107(1):316.
52. Dugue L, Sauvanet A, Farges O, Goharin A, Le Mee J, Belghiti J. Output of chyle as an indicator of treatment for chylothorax complicating oesophagectomy. Br J Surg. 1998;85(8):1147-1149.
53. Brissaud O, Desfrere L, Mohsen R, Fayon M, Demarquez JL. Congenital idiopathic chylothorax in neonates: Chemical pleurodesis with povidone-iodine (betadine). Arch Dis Child Fetal Neonatal Ed. 2003;88(6):F531-3.
54. GINGELL JC. Treatment of chylothorax by producing pleurodesis using iodized talc. Thorax. 1965;20:261-269.
55. Jorgensen C, Brocks V, Bang J, Jorgensen F, Rønsbro L. Treatment of severe fetal chylothorax associated with pronounced hydrops with intrapleural injection of OK‐432. Ultrasound in obstetrics & gynecology. 2003;21(1):66-69.
56. Little AG, Kadowaki MH, Ferguson MK, Staszek VM, Skinner DB. Pleuro-peritoneal shunting. alternative therapy for pleural effusions. Ann Surg. 1988;208(4):443-450.
57. Engum SA, Rescorla FJ, West KW, Tres Scherer III L, Grosfeld JL. The use of pleuroperitoneal shunts in the management of persistent chylothorax in infants. J Pediatr Surg. 1999;34(2):286-290.
58. Shimmyo T, Morita K, Mineshita M, et al. Report pleuroperitoneal shunt for chylothorax and chylopericardium in lung cancer: A case report. Ann Thorac Cardiovasc Surg. 2011;17(1):63-66.