Ascites ≈ most common complication of cirrhosis that leads to hospital admission

1. AscitesNader RoushanAssistant ProfessorDepartment of internal medicinedivision of GastroenterologyTehran University of Medical Sciences21.10.92

2. Ascites≈ most common complication of cirrhosis that leads to hospital admission • 85%ascites in US≈ cirrhosis

3. Diagnostic paracentesis≈ clinically apparent new-onset ascites • bleeding is uncommon ≈ routine prophylactic use of FFP or plateletsbefore paracentesis is not recommended.

7. SAAG ≥1.1g/dL ≈ portal hypertension ≈ 97% accuracy.

8. If ascitic fluid infection is suspected ≈culturedat bedside in aerobic and anaerobic blood culture bottles prior to initiation of antibiotics. • Other studies of ascitic fluid ≈ based on pretest probability of disease • serum CA125 is not helpful in Dx of ascites ≈ not recommended in patients with ascites of any type.

9. An ascitic fluid CEA>5ng/mLor ALP>240 units/L ≈ accurate in detecting gut perforation

10. Patients with low SAAG (<1.1 g/dL) ascites usually do not have portal hypertension and, with the exception of nephrotic syndrome, do not respond to salt restriction and diuretics. Improvement in the outcome of patients with nonportal-hypertension related ascites depends on successful treatment of the underlying disoder.

11. Secondary bacterial peritonitis: Multiple organisms (frequently including fungi and enterococcus) on Gram’s stain and culture, and at least two of The following criteria: • total protein >1g/dL, • LDH> ULN for serum, • glucose <50 mg/dL.

12. DX: • 96% sensitivity of 3 criteria and/or polymicrobial culture • CT was diagnostic in 85% of patients with 2ary peritonitis

13. Cancer is the sole cause of ascites or contributes to ascites in 7 % of pxs • Some have 2 causes for ascites (cirrhosis + peritoneal carcinomatosis) • Ascites typically develops in the setting of recurrent and/or advanced cancer

15. origin of primary tumor ≈impact on etiology of the ascites: • Malignancies of ovarian,urinary bladder ,peritoneal mesothelioma ≈ peritoneal carcinomatosis • Colonic, gastric, breast, pancreatic, and lung cancers ≈ peritoneal carcinomatosis and/or massive liver metastases ≈ obstruct/compress portal veins or liver failure • lymphomas ≈lymph node obstruction ≈ chylous

16. underlying liver disease   • Malignancy-related ascites in underlying liver disease is usu. ≈HCC • ascites may be first indication of HCC • 4 most common ≈HCC+ ascites≈ pxs with chronic HBV, chronic HCV, NAFLED, alcoholic cirrhosis • In these settings, ascites due to≈ liver failure ± portal vein (thrombosis)

17. DIAGNOSIS  •  single laboratory test ≈ + ascitic fluid cytology • clinical setting+ascitic fluid analysis+imaging • known malignancy who develop ascites frequently undergo an extensive and futile inpatient evaluation≈notinfrequently, die while hospitalized • Once px develops ascites in the setting of a nonovarian cancer, PX is usu. poor, often <3 months • Thus, approach should focus on rapid evaluation and discharge, with treatment aimed at improving quality of life • ascites in a woman with epithelial ovarian cancer ≈not limited PX

18. Physical examination • percussion of the flanks for dullness • shifting dullness • umbilical nodule ≈ Sister Mary Joseph nodule • FNA of nodule ≈ rapid DX Gastric or colon cancer, HCC, lymphoma, and rarely peritoneal mesothelioma

19. Imaging tests —  • presence of ascites, visualize liver, findings that support DX of malignancy • Ultrasound ≈ most cost-effective initial imaging • CT or MRI may also be performed depending upon the clinical setting and status of renal function.

20. ABDOMINAL PARACENTESIS • most efficient way to confirm the presence of ascites, diagnose cause, determine if the fluid is infected

21. Pink or bloody —  • Pink usu. RBC>10,000 cells/mm3 ≈ frankly bloody typically RBC tens of thousands • Ascitic fluid is bloody≈1/2 HCC and 20 % of malignancy-related ascites

22. Ascitic fluid tests • Cell count and diff — WBC ≥500 cells/mm3 ≈70 % peritoneal carcinomatosis, and cirrhosis + HCC • Peritoneal carcinomatosis can mimic SBP≈ 8% PMN≥250 • tip that the fluid is not infected ≈ predominance of lymphocytes ≈ neutrophils may reflect a response to dying tumor cells • Antibiotics can be given initially when an elevated fluid neutrophil is detected ≈ DC when DX (by +cytology and absence of growth on bacterial culture) that ascites is related to malignancy and that infection has been excluded.

23. Appearance • Clear fluid — Uninfected ascites in cirrhosis or massive liver metastases ≈ water clear if the ascitic fluid bilirubin concentration is normal +protein very low (<1 g/dL) • Turbid or cloudy — peritoneal carcinomatosis (cells) ≈ In general, high protein concentrations do not make ascitic fluid turbid≈ elevated TG as 50-100 mg/dL makes the fluid opalescent • Milky — usu. TG>serum and >200 mg/dL, and often >1000 • chylousascites≈ cirrhosis, malignancy

24. SAAG ≈ accurately identifies portal hypertension ≈ more useful than protein-based exudate/transudate • HCC +cirrhosis, massive liver metastases (± peritoneal carcinomatosis) SAAG ≥1.1 • A gradient <1.1 ≈ NO portal hypertension • peritoneal carcinomatosis -cirrhosis or massive liver metastases ≈ SAAG <1.1

25. Cultures • Bacterial cultures ≈ new onset ascites OR fever or abdominal pain • 10 mL per bottle ≈ blood culture bottles at the bedside • unusual to detect SBP ≈ in ascites due solely to peritoneal carcinomatosis

26. Protein   • mean protein ≈ in peritoneal carcinomatosis 4.0 g/Dl • 95% ≥2.5≈ when ascites solely to peritoneal carcinomatosis • always <2.5 ≈ massive liver metastases and in patients with HCC +cirrhosis

27. Glucose  • ascitic glucose similar serum unless glucose is being consumed white blood cells or bacteria • Malignant cells also consume glucose ≈ glucose may be low in peritoneal carcinomatosis • one series ≈ 70 % malignancy-related ascites ≈ <100 mg/dL and 17 %<50

28. LDH ≈ larger molecule than glucose, it enters ascitic fluid less readily • If the fluid/serum LDH >1.0 ≈ produced in or released into the peritoneal cavity ≈ usu. because of presence of tumor cells or infection • peritoneal carcinomatosis ≈ 74 %

29. Cytology • sensitivity of cytology smears for malignancy-related ascites is 58 -75 % • depends ≈number of specimens ,quality of processing, cause of malignancy-related ascites • 50 mL is sufficient • For patients with ascites related to peritoneal carcinomatosis, viable malignant cells are exfoliated into ascitic fluid ≈ 97 %of patients with peritoneal carcinomatosis had at least 1 positive ascitic fluid cytology after testing 3 samples

30. 2/3 malignancy-related ascites ≈ peritoneal carcinomatosis. • remaining 1/3 ≈ massive liver metastases, chylousascites due to lymphoma, HCC, or malignant Budd-Chiari syndrome ≈ negative cytologies • HCC metastasize to the peritoneum infrequently • Peritoneal mesothelioma≈difficult to dx cytologically, even in experienced hands ≈ It may be especially difficult to differentiate between peritoneal mesothelioma and a serous ovarian carcinoma. In some cases, peritoneoscopymay be needed with bx in order to perform IHC and electron microscopy

31. CA 125 ≈ misleading results when elevated in serum ≈ Virtually all patients, including men, with ascites or pleural fluid of any cause have elevated serum level of CA 125≈reflect shear forces on mesothelialcells≈elevatedserum levels are nonspecific • chronic liver disease + ascites averaged 321≈ When ascites is controlled, serum CA 125 decreases dramatically • ascitic fluid CA 125 ≈ not helpful test to differentiate between ascites that is due to ovarian cancer from ascites due to tumors or benign causes • we suggest against testing patients with ascites for CA 125 either in serum or in the ascitic fluid • Dx of ascites due to ovarian cancer should be made only on the basis of cytology and not upon CA 125 levels.

32. CEA   • CEA is a glycoprotein that is shed from surface of malignant cells • detectable levels of this tumor marker can be measured in the serum, and serve as indicators of disease activity • CEA is elevated in a variety of malignancies, espGI • CEA in ascitic fluid ≈ precise value in dx and DDx of malignancy-related ascites is uncertain

36. Laparoscopy • Laparoscopy + bx of peritoneal implants ≈ sensitivity for detecting peritoneal carcinomatosis≈100% • However, optimally processed cytology almost always precludes need for this invasive procedure ≈ possible exception of peritoneal mesothelioma

39. Evaluation and treatment of malignancy-related ascites