What is the appropriate workup for new ascites in a patient with known liver metastases?

Workup for New Ascites in Known Liver Metastases

Perform immediate diagnostic paracentesis with ascitic fluid analysis—this is the single most important and potentially life-saving intervention for determining the cause of new ascites in a patient with known liver metastases. 1

Initial Diagnostic Paracentesis

Diagnostic paracentesis should be performed immediately in all patients with new-onset ascites, as it is the most rapid and cost-effective method to determine etiology and can be safely performed even with coagulopathy (complications occur in only ~1% of cases, primarily minor abdominal wall hematomas). 2, 1

Essential Ascitic Fluid Tests

Order the following tests on the initial paracentesis specimen:

• Cell count with differential to detect spontaneous bacterial peritonitis (SBP) if neutrophils >250 cells/mm³ or to identify lymphocyte predominance suggesting tuberculous peritonitis or peritoneal carcinomatosis 2, 3, 1
• Albumin concentration (with simultaneous serum albumin) to calculate the serum-ascites albumin gradient (SAAG) 2, 1, 4
• Total protein concentration to help differentiate malignant ascites (typically >2.5 g/dL) from cirrhotic ascites 3, 5
• Cytology to detect malignant cells, particularly important given the known liver metastases 5
• Culture in blood culture bottles (inoculated at bedside) to exclude infection 2, 1

Optional Tests Based on Clinical Context

• Tumor markers (CEA, CA-125, CA 19-9) if peritoneal carcinomatosis is suspected 5
• Adenosine deaminase (ADA) if tuberculous peritonitis is suspected (ADA >27 U/L has 100% sensitivity and 97% specificity in cirrhotic patients) 6
• Triglycerides if the fluid appears milky or chylous 3, 5
• Amylase if pancreatic ascites is suspected 2, 5

Concurrent Blood Tests

Obtain simultaneously with paracentesis:

• Serum albumin (required to calculate SAAG) 1, 4
• Complete blood count to assess for systemic infection or cytopenias 1
• Liver function tests including bilirubin and transaminases 1
• Renal function (creatinine, BUN) to assess for hepatorenal syndrome 1
• Brain natriuretic peptide (BNP) if cardiac ascites is suspected (median pro-BNP is 6100 pg/mL in heart failure vs. 166 pg/mL in cirrhosis) 2, 1

Diagnostic Algorithm Based on SAAG

SAAG ≥1.1 g/dL (Portal Hypertension Present)

This indicates portal hypertension with 97% accuracy and suggests: 2, 3, 4

• Massive liver metastases causing portal hypertension (most likely in your patient with known liver mets)
• "Mixed ascites"—cirrhosis plus peritoneal carcinomatosis (critical not to miss this) 3
• Portal vein thrombosis from tumor
• Budd-Chiari syndrome

Key action: If cytology is positive despite SAAG ≥1.1 g/dL, this represents "mixed ascites" where both portal hypertension from liver metastases AND peritoneal carcinomatosis coexist. 3

SAAG <1.1 g/dL (No Portal Hypertension)

This suggests: 3, 4

• Peritoneal carcinomatosis (most common in malignancy without massive liver involvement)
• Tuberculous peritonitis (especially if lymphocyte-predominant ascites with protein >2.5 g/dL) 3, 6
• Nephrotic syndrome

Imaging Studies

Abdominal imaging should be performed to evaluate: 2

• Extent of liver metastases and whether massive enough to cause portal hypertension
• Portal vein thrombosis (tumor thrombus vs. bland thrombus) 2
• Hepatic vein thrombosis (Budd-Chiari syndrome) 2
• Peritoneal nodularity suggesting peritoneal carcinomatosis
• Hepatocellular carcinoma screening if underlying cirrhosis is present 2

Ultrasound can confirm ascites if physical examination is equivocal (particularly in obese patients), but imaging alone cannot determine etiology. 2

Critical Pitfalls to Avoid

• Do not delay paracentesis—physical examination alone (shifting dullness requires ≥1500 mL fluid) is insufficient for diagnosis and cannot determine etiology. 2, 3
• Do not withhold paracentesis for coagulopathy—prophylactic fresh frozen plasma or platelets before paracentesis is not recommended, as bleeding complications are rare (1/1000 procedures). 2
• Always consider "mixed ascites"—patients with liver metastases may have both portal hypertension (SAAG ≥1.1) AND peritoneal carcinomatosis, requiring cytology even when SAAG suggests portal hypertension. 3
• Check for SBP on every tap—even in malignant ascites, spontaneous bacterial peritonitis occurs frequently and requires immediate antibiotics if neutrophils >250 cells/mm³. 2, 1
• Measure ascitic fluid protein—high protein (>2.5 g/dL) with lymphocyte predominance strongly suggests tuberculous peritonitis or peritoneal carcinomatosis rather than simple portal hypertension. 3

Prognostic Considerations

Malignant ascites portends poor prognosis with median survival of 5.7 months from ascites diagnosis, and independent adverse prognostic factors include liver metastases, low serum albumin, and cancer type. 7 In metastatic pancreatic cancer specifically, ascites development leads to an 8.9-fold increased risk of death with median survival of only 1 month thereafter. 8