Dietary fats in the form of long-chain triglycerides are transformed into chylomicra and very-low-density lipoproteins. These are secreted into the intestinal lacteals and lymphatics and are then conveyed to the cisterna chyli, which overlies the anterior surface of the second lumbar vertebra, posterior to and to the right of the aorta. Usually, one major lymphatic vessel, the thoracic duct, leaves the cisterna chyli and passes through the esophageal hiatus of the diaphragm into the thoracic cavity. The thoracic duct ascends extrapleurally in the posterior mediastinum along the right side of the anterior surface of the vertebral column and lies between the azygos vein and the descending aorta in close proximity to the esophagus and the pericardium. At the level of the fourth to sixth thoracic vertebrae, the duct crosses to the left of the vertebral column and continues cephalad to enter the superior mediastinum between the aortic arch and the subclavian artery and the left side of the esophagus.

Once the thoracic duct passes the thoracic inlet, it arches 3 to 5 cm above the clavicle and passes anterior to the subclavian artery, vertebral artery, and thyrocervical trunk to terminate in the region of the left jugular and subclavian veins. Wide anatomic variations may exist in all portions of the thoracic duct. More than one thoracic duct may leave the cisterna chyli. The duct may continue on the right side of the vertebral column to enter the veins in the right subclavian region. Multiple anastomoses usually exist between various lymphatic channels, and direct lymphaticovenous communications with the azygos vein may be present (2,3).

The drainage from the thoracic duct is called chyle. Chyle appears grossly as a milky, opalescent fluid that usually separates into three layers upon standing: a creamy uppermost layer containing chylomicrons, a milky intermediate layer, and a dependent layer containing cellular elements, most of which are small lymphocytes (4). If the patient has not eaten, however, chyle may be only slightly turbid because its lipid content will be reduced. Chyle is bacteriostatic and does not become infected even when it stands at room temperature for several weeks (5). Lampson (5) reported that Escherichia coli and Staphylococcus aureus were unable to grow in 100% chyle. Chyle that is extravasated into the pleural cavity is not irritating and usually does not evoke the formation of a pleural peel or a fibroelastic membrane.

Each day, between 1,500 and 2,500 mL of chyle normally empties into the venous system (6). The ingestion of fat can increase the flow of lymph in the thoracic duct by 2 to 10 times the resting level for several hours (7). Ingestion of liquid also increases the chyle flow, whereas the ingestion of protein or carbohydrates has little effect on the lymph flow (7). The protein content of chyle is usually above 3 g/dL, and the electrolyte composition of chyle is similar to that of serum (7).

The primary cell in chyle is the small lymphocyte, and lymphocyte counts range from 400 to 6,800/mm³ (4). Prolonged drainage of a chylous pleural effusion can result in profound T-lymphocyte depletion. Breaux and Marks (8) reported that the total peripheral lymphocyte count fell from 1,665 to 264/mm³ with 14 days of chest tube drainage in one patient with a chylothorax. Almost all the lymphocytes in the pleural fluid were T lymphocytes.

A chylothorax results when the lymphatic duct becomes disrupted. Ligation of the thoracic duct at any point in its course does not produce a chylothorax in experimental animals (6), presumably as a result of the many collateral vessels and lymphaticovenous anastomoses. Ligation of the superior vena cava produces chylothorax approximately half the time in experimental animals. In the experimental animal, laceration or transection of the thoracic duct does not always produce a chylothorax. Hodges et al. (9) produced a 2.5-cm longitudinal laceration of the thoracic duct in three dogs at the level of T9 and transected the thoracic duct at this level in three other dogs. They reported that all animals developed a pleural effusion but that the effusion ceased to form after 2 to 5 days in the animals with lacerations and after 4 to 10 days in the animals with transections (9). Lymphangiograms demonstrated that there was no continuity of the thoracic duct in animals with transections and researchers concluded that lymph was being conveyed by collaterals (9).

The causes of 143 chylothoraces from five separate earlier series (6,7,10,11,12) are tabulated in Table 26.1. The causes of 203 chylothoraces seen at the Mayo Clinic between January 1980 and December 2000 were as follows: surgery or trauma, 101 patients (49.8%); malignancy, 34 (16.7%); congenital or acquired lymphatic disorders, 19 (9.4%); chylous ascites, 16 (7.9%); miscellaneous medical causes, 20 (10%); and no identifiable cause, 13 (6.4%) (13). The differences in the distribution of the diagnoses in this latter study compared with the former studies may be due in part to the fact that the Mayo Clinic is a tertiary referral center and that the distribution of diagnoses is changing with time.

For convenience, the causes of chylothorax can be grouped into four different categories, namely, trauma, tumor, miscellaneous, and idiopathic (14). Trauma is the leading cause of chylothorax. This trauma is usually a cardiovascular, pulmonary, or esophageal surgical procedure. Chylothorax appears particularly frequently following operations in which the left subclavian artery is mobilized (15). The incidence of chylothorax after most thoracic surgeries is less than 1.0%. The incidence of chylothorax was 0.5% in one series of 2,660 cardiovascular operations (16), whereas it was 2.4% in a series of 1,110 lobectomies and pneumonectomies with systematic mediastinal lymph node dissection (17). The incidence of chylothorax is relatively high in children undergoing cardiothoracic surgery. In one series of 1,257 surgeries, there were 48 cases of chylothorax (3.8%) (18). The incidence exceeded 10% in patients undergoing the Fontan procedure, heart transplantation, and repair of the Tetralogy of Fallot (18). The incidence of chylothorax following esophageal resection is relatively high; it was 3.8% in one series of 892 cases (19). Dougenis et al. (20) reported that the incidence of chylothorax following esophageal surgery was significantly higher when the main thoracic duct was not ligated at the time of the resection. A subsequent study (21) randomized 653 patients undergoing esophageal resection to undergo or not undergo thoracic duct ligation. They reported that the incidence of chylothorax in the treatment group (0.3%) was significantly less than in the control group (2.1%) (21).
Chylothorax has also been reported as a complication of coronary artery bypass surgery when the internal mammary artery is harvested (22), heart transplant (23), high translumbar aortography (24), sclerotherapy for esophageal varices (25), thoracolumbar fusion for correction of kyphosis (26), and cervical node dissection (27).

Of course, penetrating trauma to the chest or neck such as gunshot or knife wounds can also sever the thoracic duct and may lead to chylothorax. Trauma in which the spine is hyperextended or a vertebra is fractured is most likely to cause chylothorax, particularly if the injury occurs after the recent ingestion of a fatty meal (27). A chylothorax secondary to closed trauma is usually on the right side, and the site of rupture is most commonly in the region of the 9th or 10th thoracic vertebra (27). Such trauma includes falls from a height, motor vehicle accidents, compression injuries to the trunk, heavy blows to the back or stomach, and childbirth (28). The injury may be less impressive, and chylothoraces have been attributed to coughing, vomiting, and weight lifting. In one well-documented case report, an episode of vigorous stretching while yawning was followed by swelling in the left supraclavicular fossa and the development of bilateral chylothoraces (29).

Another leading cause of chylothorax is malignancy. The most common malignancy to cause a chylothorax is a lymphoma, and lymphomas accounted for 75% of the chylothoraces due to malignancies are listed in Table 26.1. In the series from the Mayo Clinic (13), lymphomas (20 non-Hodgkin lymphoma and 3 Hodgkin disease) accounted for 68% of the chylothoraces due to malignancy. Other malignancies producing a chylothorax in the Mayo Clinic series included chronic lymphocytic leukemia 5, metastatic disease 5, and lung cancer 1 (13). Chylothorax may be the presenting symptom of lymphoma (7,11,15). Therefore, a nontraumatic chylothorax is an indication for a diligent search for a lymphoma. In the series of Roy et al. (11) before the availability of computed tomographic (CT) scans, the diagnosis of lymphoma was not established until 6 to 12 months after the appearance of the chylothorax in four patients.

The third category of chylothorax is the miscellaneous category. Thrombosis of the superior vena cava or the subclavian vein is becoming one of the more common causes of chylothorax. Berman et al. (30) reviewed the case histories of 37 infants and children with thrombosis of their superior vena cava in a newborn and pediatric intensive care unit and reported that 9 (24%) had a chylothorax. We reviewed cases of the superior vena caval syndrome at my previous hospital over a 6-year period and found that chylothorax complicated 4 of 76 cases (31). Chylothorax can also complicate innominate vein (32) or left subclavian vein thrombosis (33). Cirrhosis is a relatively common cause of chylothorax. Romero et al. (34) analyzed 24 cases of chylothorax occurring at their institution and reported that 5 (21%) were secondary to cirrhosis. Interestingly, the mean protein level in these five chylothoraces was only 1.7 g/dL (compared with 4.1 g/dL in the other chylous effusions), the mean lactate dehydrogenase (LDH) level was only 96 IU/L (compared with 351 IU/L in the other chylous effusions) and ascites was present in three of the five patients (34). On rare occasions, a chylothorax is associated with heart failure or the nephrotic syndrome and the effusion is also a transudate in these instances (35). In most patients with the nephrotic syndrome and a chylothorax, the chylothorax is secondary to chylous ascites, but on occasions, it can be secondary to superior vena caval thrombosis (36).

Many other causes of chylothorax have been reported, but even when all are grouped together, they account for only a small percentage of chylothoraces. The most interesting of these is pulmonary lymphangioleiomyomatosis (LAM), which has associated interstitial parenchymal infiltrates, and is discussed later in this chapter. Other causes include Gorham syndrome (37) (also discussed later in this chapter), Kaposi sarcoma in patients with acquired immunodeficiency syndrome (AIDS) (38,39), the yellow nail syndrome (14), filariasis, paragonimiasis (40), giant lymph node hyperplasia (Castleman disease) (41), lymphangiomatosis (42), familial lymphedema (43), lymphangitis of the thoracic duct, obstruction of the superior vena cava secondary to Behçet syndrome (44,45), tuberculosis (46), sarcoidosis involving the intrathoracic lymph nodes (47), aneurysms of the thoracic aorta that erode the duct, abnormalities of the lymphatic vessels such as intestinal lymphangiectasis (48) or reticular hyperplasia (12,49), radiation-induced mediastinal fibrosis (50), and hypothyroidism (51).

The fourth category of chylothorax is idiopathic, including most cases of congenital chylothorax. One should exclude lymphoma as a cause of the chylothorax before it is labeled idiopathic. Most cases of idiopathic chylothorax in the adult are probably due to minor trauma, such as coughing or hiccupping, after the ingestion of fatty meals.

Chylothorax is the most common form of pleural effusion encountered in the first few days of life (52). The fetal pleural effusion discussed in Chapter 20 is probably also a chylothorax. Neonatal chylothorax is relatively uncommon; during a 22-year period, 12 cases were diagnosed at the Hospital for Sick Children, which is a large pediatric tertiary care center (53). The babies are usually born at full term after normal labor and delivery. The etiology of congenital chylothorax is unknown (54). Abnormalities of the thoracic duct have not been found in most babies who have undergone exploratory thoracotomy (52). Several cases of generalized pleural oozing have been described during surgery (53). It is possible that birth trauma may result in a tear of a major lymphatic channel in at least some individuals. Most neonatal chylothoraces represent pleural effusions that had been present antenatally. In some cases, a congenital chylothorax is associated with Turner’s syndrome, Noonan’s syndrome, or Down’s syndrome (54). Congenital chylothorax is also more common in infants who are hydropic or who have polyhydramnios (53).

Interestingly, mice that lack the integrin α₉ β₁ appear normal at birth but then develop respiratory failure and die between 6 and 12 days of age (55). The respiratory failure is caused by bilateral chylothoraces. Although the thoracic duct appears normal grossly, microscopic examination reveals edema and lymphocytic infiltration in the chest wall (55). Members of the integrin family of adhesion receptors mediate both cell-cell and cell-matrix interactions and have been shown to play vital roles in embryonic development, wound healing, and other biologic processes. It has been postulated that integrin α₉ β₁ deficiency could be one cause of congenital chylothorax (55).

The initial symptoms of chylothorax are usually related to the presence of the space-occupying fluid in the thoracic cavity, and, therefore, patients have dyspnea. On rare occasions, the patient can develop a tension chylothorax with compromise of the systemic circulation (56). Pleuritic chest pain and fever are rare because chyle is not irritating to the pleural surface. With traumatic chylothorax, a latent period of 2 to 10 days usually occurs between the trauma and the onset of the pleural effusion (27). There is one case report in which the latent period was 11 weeks (57). Lymph collects extrapleurally in the mediastinum after the initial thoracic duct disruption, forms a chyloma, and produces a posterior mediastinal mass (3). The mediastinal pleura eventually ruptures, chyle gains access to the pleural space, and dyspnea is produced by the chyle compressing the lung. At times, hypotension, cyanosis, and extreme dyspnea occur when the chyloma ruptures into the pleural space. The ruptured chyloma is no longer visible radiographically.

With nontraumatic chylothorax, the onset of symptoms is usually gradual. In congenital chylothorax, the infant develops respiratory distress in the first few days of life; 50% of patients have symptoms within the first 24 hours, whereas 75% have symptoms by the end of the first week (52). The chyle production in a neonate may exceed 250 mL/day (54).

The main threat to life from chylothorax is malnutrition and a compromised immunologic status. Because the thoracic duct carries 2,500 mL of fluid daily that contains substantial amounts of protein, fats, electrolytes, and lymphocytes, the patient can become cachectic rapidly if this amount of chyle is removed daily through chest tubes or repeated thoracentesis. In addition, the patients develop lymphopenia and a compromised immunologic status because of the removal of large numbers of lymphocytes with the chyle (58). In one case report, one patient had more than 35 L of fluid withdrawn over a 14-day period that contained 2.3 kg of fat and 0.7 kg of protein. During this period, the peripheral lymphocyte count dropped from 1,665 to 264/mm³ (8). Indeed, until Lampson initially described successful ligation of the thoracic duct in 1948 (5), the mortality rate from chylothorax was 50%. When managing a patient with chylothorax, one should abandon conservative treatment before the patient becomes too malnourished and immunocompromised.