Treatment Options in Patients With Chylothorax
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Background: Chylothorax arises when lymphatic fluid (chyle) accumulates in the pleural cavity because of leakage from lymphatic vessels. It is most commonly seen after thoracic surgery (in 0.5% to 1% of cases) and in association with tumors. No prospective or randomized trials have yet been performed to evaluate the available treatment options.
Methods: This review is based on a selective search of the PubMed database for pertinent publications from the years 1995 to 2013. Emphasis was laid on articles that enabled a comparative assessment of treatment options.
Results: Initial conservative treatment (e.g., parenteral nutrition or a special diet) succeeds in 20% to 80% of cases. When such treatment fails, the standard approach up to the present has been to treat surgically, e.g., with ligation of the thoracic duct, pleurodesis, or a pleuroperitoneal shunt. The success rates of such procedures have ranged from 25% to 95%. Most of the patients undergoing such procedures are severely ill; complication rates as high as 38% have been reported, with mortality as high as 25%. In more recent publications, however, morbidity and mortality were lower. Interventional radiological treatments, such as percutaneous thoracic duct embolization or the percutaneous destruction of lymphatic vessels, succeed in about 70% of cases and lead to healing in up to 80% of cases, even after unsuccessful surgery. The complication rate of percutaneous methods is roughly 3%.
Conclusion: Interventional radiological procedures have now taken their place alongside conservative treatment and surgery in the management of chylothorax, although they are currently available in only a small number of centers.
Chylothorax is by definition a collection of chyle in the pleural cavity resulting from leakage from the lymphatic vessels, usually from the thoracic duct. The symptoms of chylothorax can occur in patients of any age; the condition has multiple possible causes, and may therefore be encountered in many fields of medicine. Incidence data are available for only postoperative chylothorax, which can occur after almost any surgical operation in the chest. It is most often observed after esophagectomy (about 3% of cases), or after heart surgery in children (up to about 6% of cases) (1, 2). Treatment options for chylothorax today range from the conservative to surgical and—more recently—interventional radiological procedures. Because of the rarity of the condition, no prospective studies have been carried out on how best to treat it, or for how long. For guidance, therefore, we describe the current state of the art of the diagnosis and treatment of this interdisciplinary disease entity.
The thoracic duct drains the cisterna chyli, in which the lymph from the lower half of the body and the abdominal cavity joins the chyle coming from the intestinal trunk, forming a mixture also referred to as chyle. Its typical course is shown schematically in Figure 1, although variations are seen in more than one third of the population (3, 4). Its close spatial relationships with other structures explain why it is at risk of injury during surgery along the course of this lymph drainage pathway (see below).
When the thoracic duct (or a large communicating lymph vessel) is leaky or damaged, the fluid that leaks out either collects locally and later breaks through into the pleural cavity, or it flows directly into the latter via existing pleural defects (e.g., caused by surgery). Rarely, chylothorax may occur due to transdiaphragmatic flow in a patient with chylous ascites.
Any lesions of the thoracic duct can quickly lead to the formation of large fluid collections, as the duct transports around 2 to 4 L of fluid a day (5). Different forms of chylothorax are distinguished on the basis of their etiology—traumatic, non-traumatic, and idiopathic (6) (Box)—the relative frequencies of which vary between patient populations. Today, the most common traumatic cause is chest surgery (3), e.g., esophageal resection, which leads to chylothorax in about 3% of cases (1).
With non-traumatic chylothorax, leaks in the lymphatic pathways are due to direct infiltration or to impeded flow caused by compression and accumulation (Box). Relative impeded flow can occur where there is increased lymph production, as occurs in, for example, patients with raised central venous pressure, or those with portal hypertension or liver cirrhosis (7).
Low-volume or early chylothorax is clinically silent and no different from other pleural effusions. High-volume or, especially, rapidly occurring chylothorax can lead, not just to space-occupying effects, but also to dyspnea, cough, chest pain, and hypovolemic problems. Since chyle does not itself cause inflammatory irritation, pleuritic pain and fever are both absent (10–13).
Radiologically and sonographically, chylothorax is manifest as a non-specific, usually unilateral pleural fluid collection (2, 14). Typically, thoracocentesis obtains a milky fluid, but this is seen in only about half of all cases (10, 15). Patients who are fasting (e.g., peri- or postoperative patients) or those with congenital chylothorax produce little or no chyle, so the effusion may appear serous or clear, or, after trauma, it may be tinged with blood (10, 15). A milky appearance may also be seen in pleural empyema or so-called pseudochylothorax, but these conditions can usually be distinguished on the basis of clinical features and history (11, 14, 16, e1).
The important thing is always to consider the possibility of chylothorax in the differential diagnosis of a patient with an appropriate history. Typical constellations of symptoms are a sudden, otherwise unexplained pleural effusion or, in a postsurgical patient returning to normal nutritional intake, a marked increase in the fluid volume drained through a pleural drain (11).
Diagnostic laboratory tests
Chylothorax is diagnosed and differentiated from other forms of effusion (pseudochylothorax) on the basis of chemical analysis of the pleural fluid aspirate in a laboratory. A characteristic finding is the presence of chylomicrons – particles about 0.5 to 1.0 μm in size, made up of proteins and lipids (long-chain triglycerides), that are are absorbed and transported directly via the lymphatic pathways (2, 6, 10).
If lipoprotein analysis to demonstrate chylomicrons is not available, determining triglycerides and cholesterol will be helpful, as chylothorax is present in 99% of patients with an aspirate triglyceride content of >110 mg/dL and a cholesterol content <200 mg/dL, whereas a triglyceride concentration <50 mg/dL almost rules out chylothorax. Pseudochylothorax, which is also milky, is characterized by a cholesterol concentration of >200 mg/dL and a lower triglyceride concentration (<110 mg/dL) (cholesterol:triglyceride ratio >1). Extended fasting or malnutrition can lower the triglyceride concentration below these values (10, 11, 14).
Most cases of chylothorax are exudative (high protein, low lactate dehydrogenase [LDH]), but in about 25% of cases it can be transudative. Transudative effusions indicate a hepatic (portal hypertension/cirrhosis) or cardiac etiology (11, 14, 15).
Chylothorax is a condition that needs to be taken seriously: a patient who persistently loses chyle will be losing considerable amounts of fat and fat-soluble vitamins, proteins (chyle contains 12–60 g/L, depending on nutritional intake), electrolytes, immunoglobulins, and T-lymphocytes, with resulting malnutrition, weight loss, and an impaired immune system (2, 11, e2). After only 8 days of T-cell depletion due to external chyle drainage, patients are already at risk of septicemia (17). If the chylothorax is associated with a tumor, the underlying disease will also affect the prognosis.
Chylothorax requires careful and appropriate treatment, which will naturally depend on the cause and accompanying clinical conditions (e.g., effusion volume, accumulation rate, underlying disease, co-morbidities), and also on the locally available expertise (Table 1). For patients with high-volume chylothorax, especially if it is symptomatic or increasing, waiting is not an option.
Because this condition is so rare, there are no prospective or even randomized studies that give a clear answer to questions about how best to treat chylothorax and for how long. In general, conservative treatment is tried first, usually for a limited time, before more invasive measures are embarked on (12, 14) (Figure 3).
The cornerstones of treatment are adequate fluid and electrolyte replacement along with appropriate nutrition. Repeated thoracocentesis is usually only performed when improvement is expected from short-term treatment of the underlying disease, or clinical symptoms are present that only require occasional aspiration. Otherwise, in patients with high-volume or, especially, symptomatic chylothorax, continuous drainage is put in place to allow the lung to re-expand and to optimize pulmonary function (16, 20).
As part of initial conservative treatment, an attempt is made to reduce the flow of lymph through the thoracic duct to the point that the lymph leak will close up and the chytothorax eventually heal itself. The patient can be given a diet containing medium-chain triglycerides (MCT), which are absorbed directly into the portal venous system without going through the intestinal lymph vessels and the thoracic duct. It is rare, however, that these measures alone will suffice, so although it is more expensive and is associated with more problems, complete parenteral nutrition has in many places become established as the first step (5, 16).
In addition to diet, it is possible to reduce lymph flow by means of medication using somatostatin or its analog octreotide. Neither chylothorax as an indication nor the dose, method, and duration of drug administration have been confirmed or standardized in prospective studies (e19–e24) (eTable 1). If a drain output that has previously remained unchanged halves within 48 hours of the start of additional octreotide administration, this suggests that the treatment is working and the drug should therefore be continued (2, e30).
When chylothorax is non-traumatic, treatment of the underlying disease (chemotherapy, irradiation) can lead to improvement, but success rates are limited (eTable 1 and 2), ranging for example from 0% to 20% or 33% (21, 22, e7). In postoperative chylothorax, mediastinal irradiation given as an adjuvant therapy has been described, but its real value is still unclear (23).
Generally, the success rate of conservative treatment ranges from 16% to more than 75% (24–26); at output rates of more than 1000 mL/day, the success rate of conservative treatment is low (12, 14). If the lymph leak is due to direct tumor or lymphoma infiltration, it is unlikely that permanent adhesive occlusion will be induced merely by reducing the lymph flow rate (21).
Locating the exact site of a lymph leak is worthwhile only if the result is going to affect therapeutic management. Basically, a leak can be located non-invasively using radionuclides or magnetic resonance imaging (27, 28). Diagnostic MRI uses so-called fluid-sensitive sequences (analogous to magnetic resonance cholangiopancreatography, MRCP). Its accuracy in terms of locating the leak site is superior to that of radionuclide imaging, and it can be helpful in the planning of an interventional procedure (see below). Lymphography can also demonstrate a leak, but as the only invasive procedure is rarely indicated nowadays (29).
When conservative treatment failed, for a long time the only remaining treatment method was surgery, which—if used early—can reduce the mortality rate associated with chylothorax from 50% to 10% (30–32).
Operative treatment was and is regarded as indicated when, for example:
- More than (1000–)1500 mL chyle is being drained every day (in children the threshold is >100 mL/kg body weight [BW])
- For 5 treatment days drain output is up to 1000 mL/day, or, in children, 100 mL/year of age.
- A leak persists for more than 2 weeks (100 mL/day >2 weeks)
- The drain output remains unchanged over 1–2 weeks
- Clinical deterioration occurs, e.g., malnutrition or metabolic problems (2, 5, 9, 14, 16, 26, 30, e9–e11).
These guide values have not been confirmed by controlled studies. In patients with postoperative chylothorax, it must be remembered that early reoperation can put anastomoses at risk, so quite long attempts at conservative treatment are recommended, e.g., 2 to 4 weeks after esophagectomy (e5). Small children are at risk because of their delicate fluid and electrolyte balance. Early surgical treatment is recommended in young patients, those with a high-volume chyle leak, and those with a body weight below 4 kg (e12).
Table 1b summarizes the surgical options. Ligation of the thoracic duct—best established for traumatic chylothorax—is usually carried out above the right diaphragm between T8 and T12; after ligation, the lymph drains via lymphatic collaterals and lymphovenous anastomoses (13).
In general, the main difficulty in surgical treatment is identifying the thoracic duct or the leak. This becomes easier if cream is administered (e.g., intraoperatively via a stomach probe) (18). If the duct is still not identifiable, mass ligation of the tissue in the presumed course of the thoracic duct can help (12, e13).
Other problems that can lead to failure of surgery are failure to identify accessory lymphatic pathways, technically inadequate ligation, and surgical injury of the fragile duct during manipulation (25, 26).
If an operation has failed, or if thoracic duct ligation does not appear feasible or worthwhile, pleurodesis may heal the chylothorax (12, 14, 25, e4). Pleurodesis also offers a treatment option when a malignant tumor is the cause of the chylothorax. It is employed when treatment of the tumor has not resulted in sufficient improvement, or in situations where interrupting the thoracic duct is regarded as not feasible or worthwhile. It must be borne in mind that pleurodesis can only be successful in patients with expandable lungs (i.e., non-trapped lungs) (33). Creation of lymphovenous anastomoses has not become established as a therapy (e4). As a surgical last resort, creation of a pleuroperitoneal shunt or external intermittent permanent drainage through placement of a suitable catheter system may be considered (e10).
Clinically, surgical treatment is successful in about 90% of cases, although up to 11% of patients have to undergo several procedures (27).
For thoracic duct ligation, which is usually carried out in severely ill patients, complication rates of up to 38.3% and mortality rates up to 25% have been reported (16, 25, 28, e14, e15). In more recent publications, however, lower rates have been reported. This is believed to be because surgery is being performed earlier (in better time) and is less traumatic, and because better supportive measures have been introduced (e3, e9).
Today there are several radiological treatments that can be used in both traumatic and non-traumatic chylothorax (Table 1c), although some of these are still restricted to only a few centers.
In hepatic chylothorax, the portal venous pressure and hence the flow of lymph can be reduced by a transjugular intrahepatic portosystemic stent shunt (TIPS), with the result that the lymph leak site may close (adhere) spontaneously and the chylothorax heal (34).
In non-traumatic chylothorax, other radiological therapeutic possibilities have been described. After lymphography, healing of the chylothorax has been observed in about 6% to 50% of cases (35, 36). However, the therapeutic success of lymphography cannot be assessed, so given the existence of other, more effective measures, this procedure has not become an established therapy. Direct occlusion of the lymph leak site can be tried using targeted CT-guided injection of tissue adhesive near the leak (e16). Overall, there has not been much experience with these procedures.
Much more experience is available for percutaneous embolization of the thoracic duct (eTable 3), which can be performed as an alternative to thoracic duct ligation and can be performed in both adults and children (13, 30, 32, 37).
For thoracic duct embolization, first the abdominal lymph vessels, including the thoracic duct, are imaged lymphographically. After fine-needle puncture (21G) of a suitable lymph vessel (Figure 2), the thoracic duct is accessed with a thin guidewire (0.018 inch), and a microcatheter (F3) is introduced and placed below an identifiable leak (Figure 4) (4, 32, 36–38).
This technically demanding procedure cannot, however, always be performed as described, because the existence of anatomic variants means that up to 30% of patients do not have a cisterna chyli or lymph vessel that is suitable for puncture (32, e17). In these cases, the attempt may be made to “scratch” any prevertebral small lymph pathways identified lymphographically with a puncture needle (“needle disruption”) and to reduce the flow of lymph by this means (4, 32, 39). In about one third of patients treated in this way, this leads to healing of the leak (32, e17). Embolization has a much higher success rate: if the thoracic duct can be intubated successfully, the procedure is successful in well over 90% of cases (13, 30, 32, 37). Percutaneous embolization can even lead to healing in patients who have been unsuccessfully treated with surgery (4) (eTable 3).
Clinical success depends on the underlying disease. The success rate is lower for non-traumatic than for traumatic chylothorax (36). Clinical success was achieved in 52% of cases of non-traumatic chylothorax (18, 34); for combined conservative/surgical treatment in these patients, success rates of 27% to 68% have been reported (29).
With a complication rate of around 3% and no complications with fatal outcome reported so far, percutaneous thoracic duct embolization is a relatively safe procedure (4, 13, 37, e16). In one long-term study, chronic leg swelling was observed in 7% of patients, and chronic diarrhea in about 12%. Whether these findings are a consequence of the procedure remains unknown at present (40).
The authors are grateful to Maryam Toliati, Radiology Department, Bonn University Hospital, for the graphic illustration.
Conflict of interest statement
The authors declare that no conflict of interest exists.
Manuscript received on 29 July 2013, revised version accepted on 2 October 2013.
Translated from the original German by Kersti Wagstaff, MA
Prof. Dr. Hans Heinz Schild
53105 Bonn, Germany
@For eReferences please refer to:
Department of Internal Medicine I at the University Hospital of Bonn: Prof. Dr. med. Strassburg
Clinic and Policlinic of Cardiac Surgery, University Hospital of Bonn: Prof. Dr. med. Welz
Clinic and Policlinic of General, Visceral, Thoracic, and Cardiovascular Surgery, University Hospital of Bonn:
Prof. Dr. med. Kalff
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