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Eur J Cardiothorac Surg 2007;32:362-369. doi:10.1016/j.ejcts.2007.04.024
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved
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Department of Cardiothoracic Surgery, The Heart Hospital, University College London NHS Trust, 16-18 Westmoreland Street, London W1G 8PH, United Kingdom
Received 12 February 2007; received in revised form 15 April 2007; accepted 18 April 2007.
* Corresponding author. Address: Harefield Hospital, Hill End Road, Harefield UB9 6JH, United Kingdom. Tel.: +44 1895 823737; fax: +44 1895 828666. (Email: suku50{at}hotmail.com).
| Abstract |
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Key Words: Lymph Thoracic duct Chylothorax
| 1. Introduction |
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| 2. Anatomy of the thoracic lymphatic system |
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The thoracic duct has an approximate length of 36–45 cm and a diameter of 2–3 mm. It drains intestinal chyle to the bloodstream and the lymphatics of the body, except for the right side of the head and neck, right upper limb, right lung, right side of the heart and the convex surface of liver which in turn drain by the right lymphatic duct.
Significant variations to the above-described pattern can occur. Embryologically, the thoracic duct is a bilateral structure and hence many anatomical variations are possible. The pattern described above is true only in about 65% of the population [1]. The thoracic duct duplicates or triplicates itself in more than 40% of the population [1–4]. These branches may coalesce to form a plexus in the mid portion of the duct and end independently or as one duct [5]. Infrequently, the upper portion of the thoracic duct divides into two branches that drain separately, one in the usual manner and the other reaching the right subclavian vein [5]. This variation from the normal anatomical pattern explains the incidence of chyle leak despite care and attention the surgeon might have practised in identifying and protecting the main thoracic duct during an operation such as oesophagectomy.
| 3. Biochemistry of chyle |
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Table 1 shows the general composition of chyle. Those fatty acids with fewer than 10 carbon atoms in the chain are absorbed directly by the portal venous system. This particular fact forms the basis for the use of medium-chain triglycerides as an oral diet in the conservative management of chylothorax.
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| 4. Mechanism of chylothorax |
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Mediastinal lymphadenopathy can in turn lead to chylothorax. The enlarged lymph nodes compress the lymphatic channels and thoracic duct and impede centripetal drainage of lymphatic flow from the periphery of lung parenchyma and pleural surfaces. This leads to diffuse extravasation or oozing of chyle and lymph into the pleural space.
4.1 Rare mechanisms leading to chylothorax
In hepatic chylothorax, chylous ascites crosses the diaphragm and accumulates in the pleural space. The abdominal source of chylothorax can be demonstrated by intraperitoneal injection of a radioisotope (99mTc-sulphur colloid) [8]. Chyloperitoneum results from leakage of chyle into the peritoneal cavity. Chylothorax as a complication of chyloperitoneum has been observed in various clinical conditions. As in hepatic chylothorax, chylous fluid from chyloperitoneum can cross over to the pleural space to cause chylothorax.
The mechanisms of chylothorax in idiopathic causes of chylothorax, such as Down's syndrome and Noonan's syndrome, are unclear. The mechanisms involved behind chylothorax in Noonan syndrome may be multifactorial such as congenital heart disease, coagulation-factor deficiency, pterygium colli, and lymphangiomatosis of the pleura, lungs, and chest wall.
Yellow-nail syndrome, defined as a triad of slow-growing yellow nails, lymphoedema, and pleural effusion, is due to hypoplastic or dilated lymphatics [9,10]. Bilateral chylothoraces are more common in yellow-nail syndrome.
| 5. Effect of chylothorax |
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Continued loss of proteins, immunoglobulins, and T-lymphocytes into the pleural space leads to immunosuppression [12,13]. Furthermore, B-lymphocyte-mediated immune functions are impaired by prolonged chyle drainage [12,13]. These factors predispose the patient to opportunistic infections [14]. However, infection of a chylothorax itself is very uncommon because chyle is inherently bacteriostatic.
The bioavailability of certain drugs could be severely impaired in the presence of significant chyle leak. Sequestration of drugs in chyle should be recognised early, to prevent subtherapeutic plasma levels in patients undergoing drainage of chylothorax. There are reports of this phenomenon causing subtherapeutic digoxin [15], amiodarone [16] and cyclosporine [17] levels in the serum of patients.
| 6. Aetiological classification of chylothorax |
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Other surgical procedures in the vicinity of the thoracic duct can inadvertently damage the thoracic duct. Laceration of the thoracic duct during catheterisation of the subclavian vein can lead to a chyle leak. Extensive venous thrombosis complicating central venous catheterisation has resulted in bilateral chylothorax and chylopericardium [22]. Thoracic duct injury can occur following hyperextension of the cervical vertebral column and fracture-dislocation of the spine [23]. Isolated thoracic duct injuries as a result of penetrating chest trauma have resulted in chylothorax [24].
Non-iatrogenic causes are responsible for approximately 20% of cases of traumatic chylothorax. Malignant obstruction of the thoracic duct is the commonest cause of nontraumatic chylothorax. Among the neoplastic aetiologies for chylothorax, lymphoma accounts for 70% of cases [20]. One of the less-recognised aetiologies of the chylothorax is hepatic cirrhosis [20]. As mentioned before, chylous pleural effusion results from the transdiaphragmatic passage of chylous ascitic fluid. Majority of hepatic chylothoraces are right-sided in occurrence.
Primary lymphatic disease is an uncommon cause of chylothorax. Mediastinal megalymphatics, congenital atresia of the thoracic duct [25] and localised chylous leak from the hilum of the lung can all lead to a chylothorax. Chylothorax can also occur as both an early or late complication of mediastinal radiotherapy when administered for a multitude of indications [26].
Lymphangioleiomyomatosis is an uncommon progressive thoracic pathology in females of childbearing age. It results in nodular and diffuse interstitial proliferation of the smooth muscle in the lungs, lymph nodes, and thoracic duct. Two-thirds of the patients have chylous pleural effusion [27–29]. Gorham's disease, also known as massive osteolysis, is a rare disorder in which vascular channels dilate within medullary bone and destroy the bone [30]. Chylothorax, as a result of leakage of chyle from lymphatic networks, is a life-threatening complication accompanying Gorham's disease of the thoracic skeleton [31]. Incidence of chylothorax complicating Gorham's disease is about 17% [31].
| 7. Clinical features of chylothorax |
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Chylothorax may be the initial manifestation in many patients. This mode of presentation is more likely in patients with occult lymphoma or malignancy involving thoracic lymph nodes. Insidious onset of chylous pleural effusion is a common feature in patients with lymphangioleiomyomatosis. Such patients usually present with chest discomfort and dyspnoea, or pleural effusion as an incidental finding on chest radiograph.
| 8. Investigations |
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Chest roentgenography with lateral views as well as decubitus views may be helpful in determining the size and location of the chylothorax. In complicated cases, other imaging techniques such as computed tomography (CT) of thorax may be required. CT is useful when chylothorax is associated with trauma, or where an underlying tumour is suspected. Patients with chylothorax and no obvious trauma should undergo CT of the chest to assess the mediastinum and hila for enlarged lymph nodes. Bipedal lymphangiography has been recommended to identify the cause and detect the site and size of the leak [33]. Lymphangiography can help detect anastomotic leaks in the postoperative patients and complete transection or partial laceration of the duct [34,35].
Oral or nasogastric tube feeding of food with high fat content in patients with suspected chylothorax results in a dramatic change in the colour and biochemical constituents of pleural fluid [36]. Though in human subjects there is no compelling evidence to favour, a fat meal mixed with methylene blue leads to bluish-green discolouration of the pleural fluid in chylothorax, thereby helping at times to localise the leak. Some have recommended this technique as a diagnostic test for chylothorax. However, methylene blue staining of the fat meal may not be helpful in post-traumatic chylothorax since discolouration of pleural fluid can also occur in patients with oesophageal perforation.
The most important diagnostic step is thoracentesis to obtain a sample of pleural fluid for biochemical and other analyses. The appearance of the pleural fluid can be misleading because not all chylous pleural effusions appear milky white or whitish. Approximately 50% of patients may demonstrate bloody, yellow or green turbid, serous, or serosanguineous effusions [37]. The usual milky appearance of the effusion may also be seen in pseudochylothorax or in empyema where the purulent fluid contributes to the whitish colour. Even though typical chylous fluid appears creamy or milky white, the definitive diagnosis of a chylous pleural effusion is based on presence of chylomicrons in the fluid. Chylomicrons stain with Sudan III stain and cytological preparations of pleural fluid thus stained may help identify chylomicrons. However, quantitative criteria have not been established for the diagnosis of chylous pleural effusion based on Sudan III stain of cytological preparations. Normally, the diagnosis of chylothorax is based on the biochemical analysis of pleural fluid. Lipoprotein analysis of pleural fluid will confirm the presence of chylomicrons. Even though the presence of chylomicrons in the pleural fluid is synonymous with chylothorax, lipoprotein analysis is not available in all medical centres. In lieu of lipoprotein analysis, quantitation of triglyceride in pleural fluid can be used to diagnose chylothorax.
Pleural fluid triglyceride levels have been used in diagnosing chylothorax®. Pleural fluid triglyceride levels >110 mg/dl, presence of chylomicrons, low cholesterol level, and elevated lymphocyte count are diagnostic of a chylothorax. When the pleural fluid triglyceride level is >110 mg/dl, there is <1% chance of it not being chylous, and pleural fluid with a triglyceride value of <50 mg/dl has no more than a 5% chance of being chylous. When the triglyceride level is between 55 and 110 mg/dl, a lipoprotein analysis is indicated to detect chylomicrons. Other criteria for chylothorax include a pleural fluid to serum triglyceride ratio >1, and a pleural fluid to serum cholesterol ratio <1.
In hepatic chylothorax, pleural effusion is usually a transudate, and has lower cholesterol (22–64 mg/dl) levels than chylous effusions resulting from other causes [8]. In a given patient, the biochemical characteristics of hepatic chylothorax are identical to those of ascitic fluid. In hepatic chylothorax, the abdominal source of chylothorax can be demonstrated by scintigraphy after the intraperitoneal injection of a radioisotope (99mTc-sulphur colloid), with the appearance of radioisotope in the pleural cavity within 90 min [8].
| 9. Pseudochylothorax versus chylothorax |
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High cholesterol levels are typical of a pseudochylous pleural effusion. Cholesterol levels are generally >200 mg/dl and may even exceed 1000 mg/dl [39]. The fluid may demonstrate rhomboid-shaped cholesterol crystals on microscopy, which do not stain with Sudan III stain [39]. The precise origin of cholesterol in pseudochylothorax is unknown, but it is attributed to the continued breakdown of chronic inflammatory cells in a long-standing effusion. Tuberculosis pleural effusions account for approximately 54% of all cases [40]. Rheumatoid arthritis and trapped lung syndrome are rare causes of pseudochylothorax [41].
Pseudochylous pleural effusions are usually sterile and require no treatment, unless they are large and cause progressive respiratory symptoms. In symptomatic patients, management with pleural drainage, alone or in combination with specific therapy is indicated. Complicated cases or tuberculous pseudochylothorax that leads to progressive respiratory distress may require pleural decortication.
| 10. Management of chylothorax |
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Malignant chylothorax has been treated with radiotherapy and/or chemotherapy, with results that have not been consistently rewarding [43,44]. Generally, radiation therapy to a total dose of 2000 rads controls most cases of malignant chylothorax [44,45]. When surgical closure of the site of chyle leak is not practical, talc pleurodesis is an option in malignant chylothoraces [46]. One report of 19 patients with 24 chylothoraces secondary to lymphoma and refractory to chemotherapy or radiation therapy documented that talc pleurodesis via thoracoscopy under topical anaesthesia and conscious sedation resulted in a 100% success rate in the prevention of recurrence of chylothorax at 30, 60 and 90 days following the procedure [47]. Other methods to control chylothorax include phrenic nerve crush and reimplantation of the thoracic duct into a vein or re-anastomosis of a torn thoracic duct [48]. Somatostatin or octreotide infusions have been used successfully to reduce intestinal chyle production and secondarily reduce chyle leak [49–51]. Somatostatin treatment is an important adjuvant in the conservative management of chyle leak [52,53].
10.2 Surgical management
Aggressive surgical therapy is recommended for post-traumatic or post-surgical chylothorax. Mortality with conservative management of chylothoraces after oesophagectomy approaches 50% whereas with active surgical intervention, it drops to about 10% [21,54]. Many advocate conservative management for a maximum of 2 weeks in the absence of a strong indication for surgery [55,56]. Children who develop chylothorax after oesophageal surgery are more likely to develop overwhelming bacterial and fungal sepsis if a conservative approach alone is instituted [57].
The general consensus is that surgical management should be adopted if medical management fails. The clinical parameters that prompt surgical intervention and the type of intervention vary between centers. In general terms, surgical intervention offers better results than conservative management when the daily chyle leak exceeds 1.5 l in an adult or >100 ml/kg body weight per day in a child [55]. Surgical intervention is usually indicated when the chyle drainage rate is more than 1 l/day for a period more than 5 days [58].
Lymphangiography will help to delineate the anatomy of the lymphatic channels and thoracic duct as well as the site of leak, though this is laborious. Other methods which are helpful to locate the leak includes preoperative subcutaneous injection of 1% Evans blue dye in the thigh or enteral administration of a fat source like olive oil or cream. Methylene blue may be added to the fat source to highlight the site of leak.
10.3 Techniques of ligation of the thoracic duct
Basically, if the chyle leak can be identified, direct ligation with nonabsorbable suture should be performed on either side of the leak. If the site of leak is not identifiable easily, extensive dissection to find this is strongly discouraged to minimise trauma and further leaks. Mass ligation of all tissue between the aorta, spine, oesophagus and pericardium is performed above the diaphragmatic hiatus via the right pleural space. This is traditionally performed through a sixth or seventh space thoracotomy. Parietal pleurectomy helps in these cases by promoting pleural symphysis.
If the drainage volume is high or chylothorax occurs after an oesophageal operation, early re-operation should be considered. The surgical intervention of choice in thoracic duct injury is thoracic, abdominal or cervical ligation of the thoracic duct [59]. Many surgeons prefer to ligate the thoracic duct at the diaphragmatic level because this procedure has the advantage of stopping flow from any accessory ducts that may not be recognised [60,61].
Thoracoscopic ligation of thoracic duct has been well described [62–64]. After enteral feeding of about 50 ml of cream, thoracoscopy is performed under single lung ventilation. The first port is inserted in the right sixth or seventh intercostal space in the midaxillary line. A 30° scope is inserted through this port and the pleura inspected. A second port in the right eighth posterior intercostal space is used for dissection and division of the inferior pulmonary ligament. A third port in the anterior axillary line superiorly helps instrumentation to retract the lung. The pleural reflection is incised above the diaphragm. If the thoracic duct is easily identifiable at this stage it should be dissected carefully. A short segment of the duct is excised and the remaining ends clipped. If the duct is not identifiable, mass ligation of all tissue as described above is done using clips. The operation is finished with the placement of an intercostals drain. The drain can be removed when the drainage ceases with the patient on a normal diet.
Chyle leak following oesophagectomy occurs in about 10% of cases. If detected during the procedure, they should be closed immediately. Most postoperative chylothoraces in this setting do not heal with conservative management. Early surgical closure of the duct is the preferred option. Chylothorax noticed after pulmonary lobar resection is unusual. An initial course of conservative management is logical if the lung is fully expanded closing the thoracic cavity. If a large residual space remains early surgical closure of the duct is recommended. In patients with unavoidable pleural spaces with a chyle leak, pleuroperitoneal shunts may be appropriate.
When the thoracic duct is unidentifiable, talc pleurodesis could be tried. This traditional technique has a success rate of 95% and negligible morbidity [62,65]. When the chylothorax is complicated, loculated, or the site of chyle leak cannot be established, pleural decortication and surgical pleurodesis may be indicated. Fibrin glue has also been used to seal chyle leak by inducing pleurodesis [66–68].
Prophylactic ligation of the thoracic duct during oesophageal surgery has been recommended by some surgeons to prevent chylous fistula [21,69]. Some advocate routine ligation of the thoracic duct, especially with tumours of the midoesophagus [69]. The incidence of post-oesophagectomy chylothorax reduced from 9 to 2.1% when elective ligation of the major thoracic duct was performed in a series of 255 patients [69]. The preferred site for elective ligation is in the upper abdomen or lower thorax, where there is more constant anatomy [59]. In the event that the duct cannot be identified, mass ligation of the tissue with teflon-pledgetted non-absorbable sutures between the aorta and azygous vein may be performed [60]. Though this technique was originally described by Murphy and Piper [70], it was later popularised by Patterson and colleagues [60]. If the leak is in the upper thorax or neck, ligation of the thoracic duct is performed in the Poirier's triangle, located between the internal carotid artery, arch of aorta, and vertebral column [59].
Pleuroperitoneal shunts have been used but these are of limited help in idiopathic cases [69,71]. Brofman et al. found that pleuroperitoneal shunts were effective in palliation of pleural effusions in yellow nail syndrome [72]. Therapy using externalised pleuroperitoneal shunting in chylothorax after surgical correction of congenital heart disease is considered safe, effective, and minimally invasive [73]. Though attempts have been successfully made by interventional radiologists to cannulate and embolise the leaking thoracic duct, success has been limited [74] and the procedure not reproducible at many centres.
10.4 Prognosis of chylothorax
In the past, the mortality due to chylothorax was in excess of 50% [75]. Currently, the morbidity and mortality have improved due to the more aggressive management strategies adopted. Introduction of aggressive therapeutic measures to reverse the adverse effects of chyle loss has led to the lowering of mortality rates for post-traumatic chylothorax [76]. Malignant chylothorax, chronic debilitating chylothorax and bilateral chylothoraces have worse prognosis [77]. The success of managing large chyle leaks involves aggressive nutritional support and early surgical intervention when indicated. A step-wise algorithm shown in Fig. 1
summarises the management of chylothorax in adults.
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