Chylous Ascites

Etiology

The etiology of chylous ascites can be classified as follows:[3]

• Traumatic or non-traumatic.
• Inflammatory
• Postoperative
• Malignant
• Infectious
• Congenital or acquired
• Portal and non-portal determined by the presence or absence of diseases affecting the portal system pressure

In western countries, abdominal malignancy, and cirrhosis are considered the main causes of CA. In developing and eastern countries, the majority are secondary to infections, such as tuberculosis and filariasis.[3][4][5] However, a review of 190 patients with CA identified a total of 41 different etiologies. The most common cause was lymphatic anomalies (32%), which is more prevalent in the pediatric population. Malignant diseases were the second common etiology (7%). Cirrhosis and mycobacterial infections were identified as the cause of CA in 11% and 10% of the cases, respectively.[6]

Epidemiology

In 1992, a large university-based hospital estimated the incidence of chylous ascites (CA) to be approximately 1 in 20,000 admissions over 20 years. However, the incidence of CA has likely increased because of improved care and treatment of patients with cancer and their increased survival rates. CA is a morbid condition, and it is associated with high mortality rates depending on the underlying etiology (40% to 70%).[1][3][7]

Pathophysiology

The underlying cause of chylous ascites (CA) is the disruption of lymphatic flow. Lymph mainly originates in the intestine and the liver, as well as other organs in the abdomen. Long-chain triglycerides (TG) in the diet are absorbed as chylomicrons into the lymphatic system following conversion into monoglycerides and fatty acids in the small intestine. This attributes to the milky appearance of lymph due to the high content of TGs.[8]

In cases of CA, due to portal hypertension, endothelial compromise occurs due to high lymphatic pressure, leading to the dilation of lymphatic channels, which results in their rupture and CA formation. In non–portal etiology, lymph material is filtered as an exudate into the peritoneum by a fistula that is formed retroperitoneally due to congenital or acquired megalymphatics. Over time, the deposition of collagen in the basement membrane (BM) of the lymphatic channels occurs due to increased lymphatic pressure leading to a decline in the capacity of absorption of the intestinal mucosa. This can lead to protein-losing enteropathy manifested by inadequate absorption, malnutrition, and steatorrhea.[9][10]

The pathophysiology of chylous ascites (CA) varies depending on the etiology. This can be divided into three mechanisms:[3]

• Acquired Lymphatic Disruption

Acquired lymphatic disruption can be traumatic or secondary to surgical procedures. This causes dilation of the retroperitoneal lymphatics with drainage of lymph into the abdomen through a fistula between the lymphatic system and retroperitoneum. The dilation can also be a result of the increased production of lymph and the elevated pressure in the hepatic veins that are seen in cases of portal hypertension (HTN) secondary to cirrhosis and constrictive pericarditis.

• Fibrosis of the Lymphatic System

This is mostly seen in malignancies obstructing the lymphatic flow from the gut into the cisterna chyli, with leakage from the subserosal dilated lymphatics into the peritoneal cavity and lymph node fibrosis.

• Congenital Causes

Congenital anomalies such as congenital lymphangiectasia cause exudation of lymph into the peritoneal cavity causing CA.[11]

History and Physical

The evaluation of a patient with ascites should start with a thorough history and physical examination. A detailed history should describe the presenting symptoms, and include the past medical history (for example, malignancy, liver or renal diseases and inquiry about any recent trauma), family history, surgical history, history of travel, and social history.[6]

Patients with chylous ascites (CA) usually complain of painless, progressive abdominal distention that could extend over weeks to months. This is the most common symptom in up to 81% of the patients. Less common symptoms among patients with chylous ascites include pain or peritonitis in 11%, diarrhea, dysphagia (as reported in atraumatic causes due to goiter or para-esophageal hernia compressing the thoracic duct and leading to the formation of chylothorax and CA), peripheral edema, weight gain and shortness of breath, resulting from the increased abdominal pressure.[12] Other less specific symptoms include loss of appetite, fatigue, nausea, lymph nodes enlargement, fullness, fever, and night sweats.

Physical examination reveals a distended abdomen that could be tense on palpation. Classic signs to detect ascites can also be seen, such as shifting dullness and a transmission thrill (fluid wave). Surgical scars seen by inspection could suggest a traumatic etiology. Enlarged lymph nodes can be seen. Other general exam findings seen in the setting of malignancy, renal, or liver disease should be evaluated. For example, patients with cirrhosis may have characteristic physical exam findings, like cachexia, jaundice, temporal wasting, palmar erythema, spider angiomas on the chest and abdomen, gynecomastia, decreased breath sounds and dullness on chest percussion in the setting of pleural effusion, tense abdomen in the setting of ascites, caput medusae, confusion and disorientation (hepatic encephalopathy) in decompensated disease.[6]

Other physical exam findings can be related to specific syndromes like yellow-nail syndrome or Klippel-Trenaunay syndrome.

Evaluation

It is essential to obtain both blood and ascitic fluid analysis to diagnose and evaluate chylous ascites (CA). Standard blood tests are required and include a complete blood count, basic metabolic panel, lipid profile, liver function tests, total protein, albumin, lactate dehydrogenase (LDH), amylase, and lipase.[11]

The following tests are considered on a case-by-case basis and depending on the clinical presentation:

Abdominal Paracentesis

It is essential in the diagnosis of CA. CA is suspected when ascites appear milky. A triglyceride level in the ascitic fluid should be obtained, and a concentration greater than 200 mg/dL supports the diagnosis. Fat globules and leucocytes with a predominance of lymphocytes are shown after staining with Sudan III and undergoing microscopic examination. If tuberculosis is suspected, acid-fast bacilli smear, culture, and polymerase chain reaction (PCR) should be performed. Adenosine deaminase is considered both a sensitive (93%) and a specific (94%) diagnostic test for peritoneal tuberculosis, but in some cases, a peritoneal biopsy may be needed.

Lipoprotein Electrophoresis

It is considered a gold standard in the diagnosis of CA by identifying chylomicrons. Elevated ascitic fluid triglyceride levels are the best parameter for diagnosing CA. With a sensitivity and specificity of up to 95%, a recent study has suggested a triglyceride cutoff point of 187 mg/dL (2.13 mmol/L) or a range of 148 to 246 mg/dL (1.69 to 2.80 mmol/L) to establish CA.[13]

Cytology and Peritoneal Biopsy

These are important diagnostic tools in the work-up of CA.[14][15]

Computed Tomography (CT) of the Abdomen

This is useful to diagnose abdominal masses and lymph nodes in some cases of CA. Fat fluid level is the pathognomonic feature of chylous ascites on a CT scan, which can be demonstrated by positioning the patient in a supine position for some time before imaging is done. Because the specific gravity of lipids is less than that of water, it leads to the formation of a fat fluid level, which may also be seen by ultrasonography.[16][17]

Lymphangiography

It is considered a gold standard in the diagnosis of CA in cases of lymphatic obstruction. Lymphangiography and lymphoscintigraphy are effective in the selection of patients for surgery, assessment of the effects of treatment outcomes, detection of abnormalities in the retroperitoneal nodes, in addition to detection of any leakage, fistulization, and permeation of the thoracic duct.[1]

Other Tests

CA-125 could be particularly elevated in patients with cirrhosis and chylous ascites.

Treatment / Management

There are limited therapeutic options for chylous ascites. Therefore managing the underlying cause and applying conservative measures to improve patient comfort, reducing recurrence, and optimizing outcomes are the cornerstones in managing chylous ascites (CA).

Diet

A special diet is recommended that is low in fat, containing mainly medium-chain TGs, and high in protein. Medium-chain triglycerides spare the lymphatic system through absorption by enterocytes and being transported directly into the liver as free fatty acids and glycerol. When these dietary changes are insufficient, bowel rest and total parenteral nutrition (TPN) should be considered. This approach helps reduce lymphatic flow and bypasses the intestine. Nutritional consultation should be considered to help manage the TPN and select the ideal lipid formulation.[1][14][15]

Medical Therapy

Medical therapy includes different medications that may help decrease the accumulation of CA:

• Orlistat reduces the availability of fatty acids and their absorption by reversibly inhibiting the release of lipase from the stomach and pancreas.
• Somatostatin and the synthetic analog octreotide have been used in the treatment of CA. The exact mechanism of action is not completely understood. It can decrease the portal pressure (by inhibiting splanchnic vasodilation), peristalsis, intestinal absorption of fats, triglyceride concentration in the thoracic duct, and the lymph flow in the major channels. The route of administration and the half-life are different between somatostatin and octreotide. Somatostatins are administered intravenously and have a half-life of 1 to 3 minutes, while octreotide is administered subcutaneously and has a half-life of about 2 hours.[18] Octreotide has successfully been used in patients with CA secondary to pancreatitis, post-liver transplant, malignancy, portal vein thrombosis, and idiopathic causes, improving their quality of life.
• Etilefrine (adrenergic agonist) is used in treating postural hypotension due to its sympathomimetic effect. It has also been used in those who undergo esophagectomy and develop CA due to thoracic duct injury. It reduces the chyle flow by contracting the thoracic duct's smooth muscles.[19][20]
(B3)

Therapeutic Interventions

• Lymphangiography with embolization can be used in the management of CA. This is achieved by injecting glue percutaneously into a lymph node.[21] 
• Abdominal paracentesis may be a suitable temporary option. It can be complicated by electrolyte imbalance, malnutrition, and infection due to repetitive drainage. In patients with cirrhosis, albumin replacement, depending on the volume status, is recommended. Paracentesis should be used in conjunction with other conservative treatment options due to decreased efficacy when used alone.[17]
• Transjugular intrahepatic portosystemic shunt (TIPS) is reported to be a successful measure in treating cirrhotic patients who do not respond to conservative measures.[22]
• Peritoneovenous shunts can be considered in patients who do not respond to medical therapy or cannot undergo surgery. The shunt returns the chylous fluid to the blood, and by doing so, it achieves hemostasis again. Serious complications can be associated with these shunts, such as electrolyte abnormalities, septic shock, obstruction of the small intestine, disseminated intravascular coagulation (DIC), and air embolism. Also, it can be complicated by shunt occlusion due to the increased viscosity of chyle.[23]
(B2)

Surgical Therapy

Surgical interventions may be beneficial if all the conservative measures fail in treating CA. This should be considered if CA was due to congenital causes or as a result of surgery or malignancy. Laparotomy is usually performed to insert a shunt, close a fistula, or resect a malignancy.[22]

Differential Diagnosis

Chylous ascites is rare. Differential diagnosis may include:[24]

• Lymphoma or leukemia (CLL)
• Solid malignancies
• Sarcomas (Kaposi sarcoma)
• Neuroendocrine tumors
• Infections (mycobacterial infections and filariasis)
• Autoimmune diseases (like SLE or sarcoidosis)
• Pancreatitis
• Superior vena cava syndrome
• Cirrhosis
• Congenital abnormalities in the lymphatic system (primary intestinal lymphangiectasia or Waldmann disease, yellow-nail syndrome, Klippel-Trenaunay syndrome)

Prognosis

The prognosis among patients with chylous ascites (CA) depends on the underlying etiology. CA can be associated with a high mortality rate that can reach up to 40% to 70%. It can be highly morbid.[3][7] The prognosis of CA cases that are non-surgical is worse than surgical cases.[19] Although malignancies are considered a significant cause of CA, it has been reported that it is associated with improved survival when treated, especially in patients with lymphomas due to the recent introduction of better chemotherapy regimens, and monoclonal antibodies. Prior to the advent of these new protocols in chemotherapy, CA that occurred concurrently with lymphomas, usually led to poor prognosis, with a 3-month death rate of 90%.[25]

Complications

Chylous ascites contain nutrients and immunoglobulins, which get depleted due to their accumulation in the peritoneal cavity, leading to loss of fluids, impaired nutrition, electrolyte abnormalities, and suppression of immunity. Therefore, adequate diagnosis and treatment are mandatory.[2] Over time, the deposition of collagen in the basement membrane of the lymphatic channels occurs due to increased lymphatic pressure leading to a decline in the capacity of absorption of the gut mucosa. This can lead to protein-losing enteropathy.[11]