Pleural Effusion-Chylothorax

Epidemiology

Definition

Chylothorax is the Presence of Chylus (Lymph) in the Pleural Space Due to Damage to the Thoracic Duct

Incidence

Series of Patients with Chylothorax (Chest, 1992) [MEDLINE]

Nontraumatic Cases (72%)
- Malignancy (46%)
  - Lymphoma: 37%
  - Non-Lymphoma (Lung Cancer, Mediastinal Malignancy, Metastatic Extrathoracic Malignancy, Sarcoma, Leukemia): 9%
- Non-Malignant (27%)
  - Idiopathic: 14%
  - Other (Benign Tumors, Lymphangioleiomyomatosis, Intestinal Lymphangiectasis, Protein-Losing Enteropathy, Regional Ileitis, Pleuritis, Cirrhosis, Thoracic Aortic Aneurysm, Lupus, Tuberculosis, Sarcoidosis, Amyloidosis, Venous Thrombosis, Mitral Stenosis, Nephrosis, Thyroid Goiter, Tuberous Sclerosis, Lymphatic Filariasis, Congestive Heart Failure, Down Syndrome, Noonan Syndrome, etc): 13%
Traumatic Cases (28%)
- Surgical (25%)
  - Cardiovascular Surgery, Aortic Surgery, Neck Surgery, Spine Surgery, Thoracoplasty, Esophagectomy, Lobectomy, Pneumonectomy, Mediastinal Mass Resection, Bochdalek Herniorrhaphy, Transabdominal Vagotomy, Central Venous Catheter, Esophageal Endoscopic Sclerotherapy, Embolization for Pulmonary Arteriovenous Malformation, Pacemaker Insertion
- Nonsurgical (3%)
  - Penetrating/Nonpenetrating Trauma to the Neck, Thorax, or Upper Abdomen, Straining, Coughing, Yawning, Vomiting

Mayo Clinic Series of Patients with Chylothorax (Mayo Clin Proc, 2005) [MEDLINE]

General Comments
- Lower Incidence of Lymphoma-Associated Cases May Be Related to the Earlier Diagnosis of Lymphoma Prior to Development of Chylothorax
- Higher Incidence of Surgery-Associated Cases May Be Related to Mayo Clinic Being a Tertiary Referral Center with Higher Numbers of Cardiovascular Procedures
Nontraumatic Cases (50%)
- Malignancy (17%)
  - Lymphoma: 11%
  - Non-Lymphoma (Lung Cancer, Mediastinal Malignancy, Metastatic Extrathoracic Malignancy, Sarcoma, Leukemia): 5%
- Non-Malignant (XX%)
  - Idiopathic: 6%
  - Other (Benign Tumors, Lymphangioleiomyomatosis, Intestinal Lymphangiectasis, Protein-Losing Enteropathy, Regional Ileitis, Pleuritis, Cirrhosis, Thoracic Aortic Aneurysm, Lupus, Tuberculosis, Sarcoidosis, Amyloidosis, Venous Thrombosis, Mitral Stenosis, Nephrosis, Thyroid Goiter, Tuberous Sclerosis, Lymphatic Filariasis, Congestive Heart Failure, Down Syndrome, Noonan Syndrome, etc): 27%
Traumatic Cases (50%)
- Surgical (48%)
  - Cardiovascular Surgery, Aortic Surgery, Neck Surgery, Spine Surgery, Thoracoplasty, Esophagectomy, Lobectomy, Pneumonectomy, Mediastinal Mass Resection, Bochdalek Herniorrhaphy, Transabdominal Vagotomy, Central Venous Catheter, Esophageal Endoscopic Sclerotherapy, Embolization for Pulmonary Arteriovenous Malformation, Pacemaker Insertion
- Nonsurgical (2%)
  - Penetrating/Nonpenetrating Trauma to the Neck, Thorax, or Upper Abdomen, Straining, Coughing, Yawning, Vomiting

Etiology

Neoplasm

General Comments

Neoplasms Account for >50% of Chylothorax Cases

Lymphoma (see Lymphoma)

Epidemiology
- Most Common Nontraumatic Etiology (Represents 75% of Malignancy-Associated Cases)
Physiology
- Likely Results from Lymphoma Cells Invading the Wall of the Thoracic Duct
- Lymphoma Cells are Typically Not Seen in Pleural Biopsies or Biopsies of the Thoracic Duct

Lung Cancer (see Lung Cancer)

Epidemiology
- XXXX

Chronic Lymphocytic Leukemia (CLL) (see xxxx)

Epidemiology
- XXXX

Kaposi Sarcoma (see Kaposi Sarcoma)

Epidemiology
- XXXX

Mediastinal Malignancy (with/without Superior Vena Cava (SVC) Syndrome)

Epidemiology
- XXXXXXX

Multiple Myeloma (see Multiple Myeloma)

Epidemiology
- XXXX

Benign Tumors of Mediastinum

Epidemiology
- XXXX

Traumatic Chylothorax

General Comments

Trauma is 2nd Most Common Etiology of Chylothorax

Surgery/Procedures

General Comments
- Especially Common with Intrathoracic Procedures Which Involve the Left Subclavian Artery
Bochdalek Herniorrhaphy
Cardiac Pacemaker Insertion (see Cardiac Pacemaker)
Cardiothoracic Surgery (Including Thoracoscopy)
- Epidemiology
  - Chylothorax Occurs in 0.5% of Cases
Central Venous Catheter (CVC) (see Central Venous Catheter)
- Epidemiology
  - Especially Subclavian Vein Central Venous Catheter Placement in the Presence of Thrombosis
  - Especially with Misplacement of the Central Venous Catheter with Inadvertent Infusion of Lipid-Containing Total Parenteral Nutrition (TPN) into the Pleural Space (Hosp Pract, 2010) [MEDLINE] (Ann Clin Biochem, 2010) [MEDLINE]
Cervical Node Dissection
Embolization of Pulmonary Arteriovenous Malformation (see Pulmonary Arteriovenous Malformation)
Esophageal Resection (Especially Transhiatal Approach)
- Epidemiology
  - Chylothorax Occurs in 2% of Cases
Esophagogastroduodenoscopy (EGD) with Variceal Sclerotherapy (see Esophagogastroduodenoscopy)
High Translumbar Aortogram
Lung Resection (Lobectomy/Pneumonectomy) with Mediastinal Lymph Node Dissection (see Lung Resection)
- Epidemiology
  - Chylothorax Has Been Reported to Occur in 1.4% of Cases (Ann Thorac Surg, 2014) [MEDLINE]
    - Incidence is Noted to Be Higher in Patients with Pathologic N2 Disease and in Those with Robotic Resection
    - Nonoperative Therapy is Almost Always Effective
Mediastinal Mass Resection
Misplaced Nasogastric/Enteral Feeding Tube with Tip in the Pleural Space (see Nasogastric Tube)
- Epidemiology
  - Chylothorax Has Been Reported in the Setting of Nasogastric Tube Misplacement into the Pleural Space (Chest, 1985) [MEDLINE]
- Physiology
  - Inadvertent Infusion of Lipid-Containing Enteral Feeding into the Pleural Space
Neck Surgery
Peritoneovenous Shunt (LeVeen Shunt) with Superior Vena Cava Obstruction (see Peritoneovenous Shunt)
Sellate Ganglion Blockade
Spine Surgery
Thoracic Sympathectomy
Transabdominal Vagotomy

Trauma

General Comments
- Closed-Traumatic Disruptions Usually Occur on Right Side Near T9-T10
Chest Trauma
Childbirth
Coughing (see Cough)
Head and Neck Surgery
Hiccuping (see Hiccups)
Hyperextension of Spine
Penetrating Injury of Neck or Thorax
Straining
Stretching While Yawning (see Yawning)
Vertebral Fracture (Especially After Fatty Meal
Vomiting (see Nausea and Vomiting)
Weight Lifting

Neonatal Chylothorax

Neonatal Chylothorax is the Most Common Etiology of Pleural Effusion in First Few Days of Life
- Usually Right-Sided or Bilateral
- Possibly Due to Increased Fetal Venous Pressure during Delivery
- Increased Incidence with Hydramnios

Other

Amyloidosis (see Amyloidosis)

Epidemiology
- XXXX

Aortic Aneurysm (see XX)

Epidemiology
- XXXX

Behcet’s Disease (see Behcet’s Disease)

Epidemiology
- XXXX

Castleman’s Disease (Angiocentric or Giant Lymph Node Hyperplasia (see Castleman’s Disease)

Epidemiology
- XXXX

Cirrhosis (see Cirrhosis)

Epidemiology
- XXXX

Congenital Chylothorax

Physiology
- Due to Congenital Malformation of Thoracic Duct (Although Can Also Be Observed After Traumatic Childbirth)

Congenital or idiopathic disorders of the lymphatic system

Lymphangiectasia, generalized lymphatic anomaly, lymphangiomatosis, Gorham syndrome, Kaposiform lymphangiomatosis) or lymphatic conduction disorders (eg, lymphatic valve dysfunction, heart failure, cirrhosis, plastic bronchitis, pulmonary lymphatic perfusion syndrome)

Congestive Heart Failure (CHF) (see Congestive Heart Failure)

Epidemiology
- Physiology
  - Increased Central Venous Pressure

Constrictive Pericarditis (see xxxx)

Epidemiology
- XXXX

Dasatinib (Sprycel) (see Dasatinib)

Epidemiology
- Case Reports When Used in the Treatment of Chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia (XXXXX)

Down Syndrome

Epidemiology
- XXXX

Fibrosing Mediastinitis (see Granulomatous Mediastinitis and Fibrosing Mediastinitis)

Epidemiology
- XXXX
Physiology
- XXXX

Idiopathic Chylothorax

General Comments
- Epidemiology
  - Accounts for Approximately 15% (Range: 6-14%) of All Chylothorax Cases

Lymphatic Filariasis (see Lymphatic Filariasis)

Epidemiology
- XXXX

Goiter (see Goiter)

Epidemiology
- XXXX

Gorham-Stout Disease (Gorham’s Disease) (see Gorham-Stout Disease)

Clinical
- Bone Pain
- Pathological Fractures
- Chylothorax

Histoplasmosis (see Histoplasmosis)

Epidemiology
- XXXX

Immunoglobulin G4 (IgG4)-Related Pleural Disease (see XXX

Epidemiology
- XXXX

Intestinal Lymphangiectasia (Noonan’s Syndrome)

Epidemiology
- XXXX

Lymphangioleiomyomatosis (LAM) (see Lymphangioleiomyomatosis)

Epidemiology
- *Occurs in 28% of Cases

Mediastinal Lymphadenopathy (see Mediastinal Mass)

Epidemiology
- XXXX
Physiology
- XXXX

Nephrotic Syndrome (see Nephrotic Syndrome)

Epidemiology
- XXXX

Noonan Syndrome

Epidemiology
- XXXX

POEMS Syndrome

Epidemiology
- XXXX

Radiation Therapy (XRT) (see Radiation Therapy)

Epidemiology
- May Be Delayed as Long as 20 Years Later

Regional Ileitis

Epidemiology
- XXXX

Retrosternal Goiter

Epidemiology
- XXXX

Sarcoidosis (see Sarcoidosis)

Epidemiology
- XXXX

Subclavian Vein Thrombosis

Epidemiology
- XXXX

Superior Vena Cava (SVC) Syndrome (see Superior Vena Cava Syndrome)

Epidemiology
- XXXX

Systemic Lupus Erythematosus (SLE) (see xxxx)

Epidemiology
- XXXX

Thoracic Aortic Aneurysm (see Thoracic Aortic Aneurysm)

Epidemiology
- XXXX
Physiology
- Due to Erosion of Thoracic Duct

Thoracic Duct Cyst

Epidemiology
- XXXX

Thoracic Duct Lymphangitis

Epidemiology
- XXXX

Transdiaphragmatic Movement of Chylous Ascites (see

Epidemiology
- XXXX

Tuberculosis (see Tuberculosis)

Epidemiology
- May Occur with Mediastinal Involvement

Tuberous Sclerosis (see Tuberous Sclerosis)

Epidemiology
- XXXX

Turner Syndrome

Epidemiology
- XXXX

Waldenström Macroglobulinemia

Epidemiology
- XXXX

Yellow Nail Syndrome (see Yellow Nail Syndrome)

Epidemiology
- XXXX

Physiology

Anatomy (note that anatomy is variable with anomalous course in 60% of humans): lymph vessels from lower extremities and peritoneal cavity join together behind the aorta and inferior to the diaphragm to form the cisterna chyli, the origina of the thoracic duct -> thoracic duct passes through diaphragm and runs along the right paravertebral space (between the azygos vein and the aorta
- At the 3rd-4th vertebra, thoracic duct crosses into the left thorax
- Thoracic duct then turns laterally and makes a small loop in the neck region
- Thoracic duct usually empties into the left subclavian vein, between jugular and vertebral veins (however, anatomic variably occurs and it can empty into the right subclavian vein)
- Thoracic duct has valves (with thoracic motion causing forward movement of the chyle) -> allows chyle to only move forward through the duct
- There are numerous small connections of thoracic duct with veins -> this allows duct to be ligated safely
Chyle contains triglycerides, chylomicrons, protein, and lymphocytes (originating from the GI tract) -> chyle is bacteriostatic
- Normal chyle flow is 2L per day
- Chyle production increases with PO intake
- Chyle contains chylomicrons, composed of long-chain triglycerides
Chylothorax results from obstruction or disruption of the thoracic duct
Chylothorax is usually right-sided: since most of the duct is within the right hemithorax
- If thoracic duct injury occurs at the level of the aorta -> left chylothorax can occur
- If thoracic duct injury occurs at point of crossover in the thorax -> bil chylothorax can occur
Note: ligation of thoracic duct does not produce chylothorax (due to collaterals and lymphatico-venous anastomoses)

Diagnosis

CXR/Chest CT
- Pleural effusion (usually right-sided)
- Chest/Abd/Pelvic CT is necessary to exclude intrathoracic tumor (particularly lymphoma) CXR/Chest CT patterns: chyloma may occur in posterior mediastinum before chylothorax develops (disappears when mediastinal pleura ruptures into pleural space) -Pleura is normal (chyle is non-irritating)
Lymphangiogram
- Useful in some cases to demonstrate if disease is localized of diffuse
- May demonstrate leak or level of obstruction
Pleural Fluid:
- Appearance: ususlly appears thick, opalescent, whitish or coffee-colored, due to high fat content (however, only 47% of cases demonstrate the characteristic odorless, milky, turbid fluid of chylothorax)
  - Neonatal chylothorax is serous until milk is fed
- Triglyceride: elevated
  - Trig >100 mg/dL: diagnoses chylothorax (chylothorax fluid clears with addition of ethyl ether)
  - Trig <50 mg/dL: rules out chylothorax
  - Trig 50-110 mg/dL: perform lipoprotein analysis for chylomicrons to diagnose chylothorax
- Chylomicron: positive
- Centrfugation: will not clear fluid in chylothorax (as opposed to in empyema, where centrifugation will sediment the cells result in a clear supernatant)
- LDH:
- Total Protein: usually >30 g/L
- Electrolytes: same as serum
- Cells: mostly T-cells
- Ethyl Ether: causes clearing of fluid

Clinical Manifestations

Chyloma

Epidemiology: this presentation is more common after traumatic thoracic duct injury
Physiology: local chyle collection that forms acutely in the chest
- Chyle subsequently migrates into mediastinum (chylomediastinum), pericarium (chylopericardium), or into the pleural space (chylothorax)
Clinical
- Acute Chest Pain (see Chest Pain)
- Dyspnea (see Dyspnea)
- Swelling in Supraclavicular Fossa: occasional
- Tachycardia (see Sinus Tachycardia)

Pleural Effusion

Epidemiology
- Typical presentation
Clinical
- Onset
  - Non-Traumatic Cases: gradual onset
  - Traumatic Cases: subacute onset
  - May be acute with associated hypotension in some cases
- Rate of Chyle Accumulation: rate of accumulation depends on diet
  - High Fat Meal: increases chyle flow 2-10x normal for several hrs
  - Ingestion of Liquid (But not Carbohydrate or Protein): increases chyle flow
- Absence of Chest Pain and Fever: chyle is non-irritating and bacteriostatic
- Atelectasis (see Atelectasis): may be present
- Increased Risk of Infection: due to loss of lypmhocytes in chyle
- Nutritional Depletion: due to loss of protein, water, electrolytes, fats) -> exacerbated by thoracenteses, chest tube
Treatment
- Accumulation After Thoracentesis: rapidly reaccumulates

Treatment

Dietary Modification with Observation

Low-Fat Diet (with medium-chain triglycerides, which are predominantly absorbed drectly in to the blood): may decrease chyle flow
TPN: may decrease chyle flow
In traumatic cases, approximately 50% of chylothoraces will heal with conservative management

Chemical Pleurodesis

Pleurodesis (with tetracycline, bleo, talc): may be necessary, especially for malignancy-associated cases
It is generally believed that pleurodesis success rates are lower in chylothorax than for other malignant effusions

Pleuroperitoneal Shunt (see Pleuroperitoneal Shunt)

May be considered early to avoid malnutrition (especially in idiopathic cases)
Contraindication: co-existent chylous ascites
Requires daily pumping by the patient
May require replacement, in cases where shunt fails to function

Thoracoscopic Ligation of the Thoracic Duct

Ligation of duct just above the diaphragm
Usually successful and well-tolerated (due to collaterals from thoracic duct into other veins)

Mediastinal Radiation Therapy (XRT) (see Radiation Therapy)

Usually effective (in 68% of lymphoma cases and 50% of metastatic cancer cases)

References

Pleuropulmonary complications of enteral tube feedings. Two reports, review of the literature, and recommendations. Chest. 1985;88(2):230 [MEDLINE]
The management of chylothorax. Chest 1992; 102:586 [MEDLINE]
Eur Resp J 1997 ; vol. 10 no. 5 1157-1162 [MEDLINE]
Etiology of chylothorax in 203 patients. Mayo Clin Proc 2005; 80:867 [MEDLINE]
Chylothorax: aetiology, diagnosis and therapeutic options. Respir Med. 2010 Jan;104(1):1-8. doi: 10.1016/j.rmed.2009.08.010 [MEDLINE]
Chylothorax: diagnostic approach. Curr Opin Pulm Med. 2010 Jul;16(4):387-93. doi: 10.1097/MCP.0b013e328338dde2 [MEDLINE]
Iatrogenic chylothorax due to pleural cavity extravasation of total parenteral nutrition in two adults receiving nutrition through a peripherally inserted central catheter. Hosp Pract (1995). 2010;38(1):50 [MEDLINE]
Differential diagnosis of chylothorax in a patient on parenteral nutrition: a case report. Ann Clin Biochem. 2010;47(Pt 1):84 [MEDLINE]
Management of chylothorax in adults: when is surgery indicated? Thorac Cardiovasc Surg. 2011;59(4):243 [MEDLINE]
The incidence and management of postoperative chylothorax after pulmonary resection and thoracic mediastinal lymph node dissection. Ann Thorac Surg. 2014 Jul;98(1):232-5; discussion 235-7 [MEDLINE]