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Serum-ascites albumin concentration gradient and ascites fibronectin in the diagnosis of malignant ascites.

BACKGROUND: The differential diagnosis between malignant and nonmalignant ascites by using laboratory parameters has not been completely achieved so far. METHODS: The authors studied serum-ascites albumin concentration gradients ([albumin]s - [albumin]a), ascites fibronectin and various parameters in 149 consecutive patients with ascites (including Group 1: 22 patients with intraabdominal malignant lesions; Group 2: 81 patients with chronic liver disease; and Group 3: 46 patients with hepatocellular carcinoma [HCC]). RESULTS: The concentrations of fibronectin, albumin, protein, lactate dehydrogenase, and carcinoembryonic antigen in ascites were significantly higher in Group 1 than in Group 2 (P < 0.001). By contrast, the [albumin]s - [albumin]a was significantly lower in Group 1 than in Group 2 (P < 0.001). None of these parameters was useful in differentiating the ascites of chronic liver disease from that of HCC. In this study, to differentiate malignant ascites from the ascites caused by liver diseases, [albumin]s - [albumin]a (< 1.5 g/dl) and the fibronectin level in the ascites (> 100 micrograms/ml) provided diagnostic accuracy (96.8% and 95.9%, respectively) as precise as those of the levels of albumin (> 1.6 g/dl), protein (> 2.5 g/dl), and lactate dehydrogenase (> 60 U/l; 97.9%, 96.7%, and 94.8%, respectively) in ascites. These results were better than that of carcinoembryonic antigen level (> 1.5 ng/ml, 80.9%). CONCLUSIONS: The authors concluded that [albumin]s - [albumin]a offered the best method to survey malignant ascites because of its sensitivity (100%).

Albumins

Pathophysiology of elevated ascites fluid cholesterol in malignant ascites. Increased ascites to serum relation of proteins and lipoproteins in patients with peritoneal carcinomatosis as compared to patients with cirrhosis of the liver.

The existence of marked elevations of ascitic fluid cholesterol has been observed in patients with peritoneal carcinomatosis compared to patients with cirrhosis and has been found useful in differential diagnosis. This finding could be caused by an enhanced movement of plasma lipoproteins into the peritoneal cavity. To test this hypothesis we determined the fasting concentrations of total, high density lipoprotein (HDL)- and low density lipoprotein (LDL)-cholesterol, apolipoprotein-A1 (apo-A1) and apolipoprotein-B (apo-B) in serum and ascites of 17 patients with cirrhosis and 16 patients with peritoneal carcinomatosis. The movement of proteins from plasma to ascites was calculated from the ascites/serum concentration ratios of six different sized proteins with a molecular mass ranging from 54 kDa to 971 kDa. Mean values (mg/dl) for total cholesterol (92.6 vs. 21.0), HDL-cholesterol (15.6 vs. 1.8), LDL-cholesterol (63.4 vs. 16.1), apo-A1 (50.2 vs. 13.6) and apo-B (41.2 vs. 12.9) in ascites were significantly higher in peritoneal carcinomatosis than in cirrhosis. These differences could only partially be explained by the higher serum concentrations of these parameters in peritoneal carcinomatosis, but were mainly due to a lower selectivity for the movement of plasma proteins and lipoproteins into ascites (mean ascites/serum (A/S) ratio: 0.30-0.77) in peritoneal carcinomatosis as compared to cirrhosis (mean ascites/serum ratio: 0.11-0.21). In both groups about 85% of the total cholesterol in serum and ascites consisted of HDL- and LDL-cholesterol. These findings support the hypothesis that elevations in ascitic cholesterol in peritoneal carcinomatosis compared to cirrhosis are mainly caused by the increased movement of plasma HDL and LDL into the peritoneal cavity.

Apolipoprotein A-I

The serum-ascites albumin gradient is superior to the exudate-transudate concept in the differential diagnosis of ascites.

OBJECTIVE: To compare the serum-ascites albumin gradient to the exudate-transudate concept in the classification of ascites. DESIGN: Prospective collection of ascitic fluid data from patients with well-characterized causes of ascites. SETTING: Hepatology inpatient and outpatient ward and consult service of a large, urban hospital. PATIENTS: A total of 901 paired serum and ascitic fluid samples were collected from consecutive patients with all forms of ascites. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The utility of the serum-ascites albumin gradient and the old exudate-transudate concept (as defined by ascitic fluid total protein concentration [AFTP]) were compared for their ability in discriminating the cause for ascites formation. RESULTS: The albumin gradient correctly differentiated causes of ascites due to portal hypertension from those that were not due to portal hypertension 96.7% of the time. The AFTP, when used as defined in the old exudate-transudate concept, classified the causes of ascites correctly only 55.6% of the time. This resulted in part because the AFTP of most spontaneously infected samples (traditionally expected to be exudates) was low, and the AFTP of most cardiac ascites samples (traditionally expected to be transudates) was high. CONCLUSIONS: The exudate-transudate concept should be discarded in the classification of ascites. The serum-ascites albumin gradient is far more useful than the AFTP as a marker for portal hypertension, but the latter remains a useful adjunct in the differential diagnosis of ascites.

Albumins

Mobilization of malignant ascites with diuretics is dependent on ascitic fluid characteristics.

Serial ascites and plasma volumes were measured during diuresis in nine patients with ascites caused by peritoneal carcinomatosis, four patients with chylous malignant ascites, and three patients with portal hypertension-related ascites caused by massive hepatic metastases. Oral diuretics were given to achieve an adequate natriuresis on a sodium-restricted diet. During the study period (7.8 +/- 3.2 days), patients with peritoneal carcinomatosis and chylous ascites lost 0.49 +/- 0.31 and 0.51 +/- 0.42 kg/day in weight, respectively, with negligible change in ascites volumes (-0.03 +/- 0.11 and 0.02 +/- 0.09 L/day). Patients with ascites caused by massive hepatic metastasis lost 1.06 +/- 0.15 kg/day in weight (P = 0.01 for massive hepatic metastasis vs. peritoneal carcinomatosis) and 0.23 +/- 0.13 L/day of ascites (P less than 0.05 vs. other groups). Plasma volume changes were not significantly different among the three groups. Patients with edema (9/16) had a greater natriuresis and daily weight loss. Three patients with peritoneal carcinomatosis and one with chylous ascites developed renal dysfunction or symptomatic hypotension. No patient with massive hepatic metastasis developed these complications. In patients with ascites caused by peritoneal carcinomatosis or chylous malignant ascites there is no mobilization of ascites, whereas in patients with massive hepatic metastasis, ascites may be mobilized with diuretics.

Adult

Ascitic fluid analysis in peritoneal carcinomatosis: comparison of various biochemical tests with ascitic cirrhotics.

Owing to the high false-negative rate of cytological examinations, various biochemical tests have been investigated to search for an alternative method to differentiate between the most frequent causes of ascites formation, i.e. cirrhosis of the liver and peritoneal carcinomatosis. For this purpose, serum and ascitic fluid samples of 71 ascitic patients (54 due to cirrhosis of the liver and 17 due to peritoneal carcinomatosis) were prospectively and simultaneously collected. Eleven major parameters were analyzed, and, of them, ascitic fluid protein, albumin, cholesterol, fibronectin and serum-ascitic gradient of protein and albumin were found to be useful. The serum-ascitic fluid albumin gradient was not as useful as described in the literature and, if clinically applied, the best cut-off value should be raised up to 1.5 gm/dl. Neither as useful was the serum-ascitic fluid protein gradient. Ascitic cholesterol and ascitic fibronectin were more accurate than the ascitic total protein, ascitic albumin and serum-ascitic gradient of protein and albumin in the diagnosis of peritoneal carcinomatosis. Of these tests, an ascitic fluid fibronectin concentration greater than 40 micrograms/ml was the most accurate parameter (diagnostic accuracy 96.2%) that could solely help to establish the diagnosis of peritoneal carcinomatosis.

Adult

Enhancement of normal polymorphonuclear cells respiratory burst in ascitic fluid by fibronectin. Comparison between cirrhotic and malignant ascitic fluids.

The chemiluminescence (CL) response of normal peripheral blood polymorphonuclear cells (PMN) in ascitic fluids (cirrhotic = 32; malignant = 17) was studied independently of the ascitic fluid complement activity. CL response and fibronectin levels were higher in malignant ascitic fluid than in cirrhotic ascitic fluid (p less than 0.001). Addition of pure fibronectin or malignant ascitic fluids to cirrhotic ascitic fluids increased the CL response of normal PMN. These findings suggest that the susceptibility of cirrhotic patients to spontaneous bacterial peritonitis (SBP) is a multifactorial defect involving factors distinct from low C3 levels. Fibronectin is an important factor in the promotion of the respiratory burst of normal PMN stimulated by opsonized zymosan or PMA in ascitic fluid. Our results suggest that low levels of ascitic fluid fibronectin could partly explain the high susceptibility of cirrhotic patients to spontaneous bacterial peritonitis.

Adult

Prediction of the concentration of penicillins in ascitic fluid from serum kinetics and protein binding of the antibiotics in serum and ascitic fluid of dogs.

Ascites was induced in dogs by partial ligation of the inferior vena cava. Concentrations of ampicillin, penicillin G, oxacillin, cloxacillin, dicloxacillin, nafcillin, and methicillin in ascitic fluid and serum were each determined in three animals. All antibiotics were administered intramuscularly in a dose of 15 mg/kg (dry weight) for both single-dose and multiple-dose (eight doses at 4-hr intervals) studies. Binding of antibiotics to serum and ascitic fluid proteins was measured by ultracentrifugation. After single doses the highly protein-bound drugs (oxacillin, cloxacillin, dicloxacillin, and nafcillin) had lower percentages of penetration (ratio of peak in ascitic fluid to that in serum, multipled by 100) than did methicillin, ampicillin, and penicillin G, which have a lower degree of protein binding. The effect was partially overcome by repetitive doses, but five to six doses were usually required to reach equilibrium. In addition to protein binding, serum kinetics (particularly the log mean total concentration of drug in serum after multiple doses) were important determinants of antibiotic concentrations in ascitic fluid. The total antibiotic concentration in ascitic fluid at equilibrium can be accurately calculated from the log mean serum concnetration and the percentages of protein binding in serum and ascitic fluid.

Ampicillin

Comparison of spontaneous ascites filtration and reinfusion with total paracentesis with intravenous albumin infusion in cirrhotic patients with tense ascites.

OBJECTIVE: To compare the effectiveness and safety of spontaneous ascites filtration and reinfusion and total paracentesis plus intravenous albumin infusion in cirrhotic patients with tense ascites. DESIGN: Randomised trial of the two treatments. SETTING: Teaching hospital and district general hospital in Milan. PATIENTS: 45 consecutive cirrhotic patients with recurrent tense ascites and urinary sodium excretion rate less than 20 mmol/day. 35 fulfilled admission criteria and completed the study. 17 received spontaneous ascites filtration and 18 paracentesis plus albumin infusion. MAIN OUTCOME MEASURES: Body weight; urinary volume; serum and urinary electrolyte, serum fibrinogen, and plasma aldosterone concentrations; and plasma renin activity before the procedure and 24 hours and eight days afterwards. RESULTS: Both procedures were effective in all patients. Weight decreased in both groups and showed no substantial increase after eight days. In patients receiving ascites filtration, values decreased significantly (p less than 0.01) after 24 hours for platelet count (mean relative change 0.92; 99% confidence interval 0.86 to 0.98) and serum fibrinogen concentration (0.92; 0.88 to 0.98) but returned to pretreatment values after eight days; no laboratory and clinical signs of disseminated intravascular coagulation were noted. Three patients in this group had fever, which receded spontaneously. One patient in each group had dilutional hyponatraemia. CONCLUSIONS: Spontaneous ascites filtration and reinfusion is an effective treatment for tense ascites. Reinfusion of the patient's concentrated proteins provides savings without compromising safety.

Adult

Pancreatic ascites: diagnostic importance of ascitic lipase.

10 cases of pancreatic ascites are presented. Ascitic fluid lipase is complementary to the determination of ascitic amylase in the diagnosis of pancreatic ascites and may be a more reliable diagnostic indicator of pancreatic ascites on a random ascitic fluid sample. Conservative management, consisting of abdominal paracentesis with or without diurectics, proved to be the treatment of choice in 3 of our patients who failed to reveal an associated pseudocyst.

Adenocarcinoma

Reinfusion of autogenous ascitic fluid concentrated by freezing in patients with intractable ascites.

Eleven patients with intractable ascites were treated by intravenous reinfusion of concentrated autogenous ascitic fluid. The ascitic fluid was drained and centrifuged for removal of cells by a cell separator. Cell-free ascitic fluid was frozen in a medical freezer at -15 degrees C and thawed at room temperature. The fraction at the initial stage of melting contains a high concentration of protein and was thus collected and reinfused to the patient. In this initial fraction, the recovery rate of albumin was 42.0 +/- 9.0% and the concentration of protein was 7.1 +/- 2.4 g/dl. This frozen method is inexpensive and time saving, because it does not use a filter. Ascites was ameliorated in all patients with 1 to 19 times of reinfusion. Therefore, when renal function is not disturbed, the frozen method may be indicated for management of intractable ascites.

Adult

Antibiotic concentrations in ascitic fluid of patients with ascites and bacterial peritonitis.

Thirty-six paired specimens of serum and ascitic fluid from 21 patients with peritonitis and ascites, most with sponetaneous bacterial peritonitis and alcoholic cirrhosis, were assayed for antibiotic content. Antibiotics assayed and number of determinations were gentamicin, 14; tobramycin, 7; ampicillin, 5; clindamycin, 3; penicillin G, 2; cephalothin, 2; chloramphenico, 2; and cefazolin, 1. In 31 pared specimens the ascitic fluid antibiotic concentration was about one half or more of the simultaneous serum level and in 17 assays exceeded 90% of the serum level. All antibiotics studied penetrated ascitic fluid equally well. Clinical response to antibiotic therapy was good in 12 of 16 patients with culture-proven bacterial peritonitis. Antibiotic levels in ascitic fluid exceeded the minimal inhibitory concentration of the infecting organisms in all but one patient who responded. Direct intraperitoneal instillation of antibiotics does not appear to be necessary routinely; however, there may be an initial lag of several hours before antibiotic concentrations is ascites achieve therapeutic levels.

Adult

Incidence and predictive factors of first episode of spontaneous bacterial peritonitis in cirrhosis with ascites: relevance of ascitic fluid protein concentration.

To investigate the long-term probability of the appearance of the first episode of spontaneous bacterial peritonitis in cirrhosis with ascites and to identify predictors of this complication, we closely followed throughout their illness 127 patients consecutively admitted to our unit for the treatment of an episode of ascites without prior spontaneous bacterial peritonitis (follow-up period: 21 +/- 22 mo). Thirteen patients (10%) had the first spontaneous bacterial peritonitis episode during follow-up. The appearance probability of this complication is 11% at 1 yr and 15% at 3 yr. Thirty-three variables obtained at admission (including clinical data, standard liver and kidney function test results, ascitic fluid protein concentrations and hemodynamic parameters) were analyzed in relation to their value in predicting spontaneous bacterial peritonitis development. In univariate analysis (Kaplan-Meier curves) five variables reached statistical significance (p less than 0.05) as predictive factors for the development of the first spontaneous bacterial peritonitis episode. These five variables were poor nutritional status, increased serum bilirubin levels, increased serum AST levels, decreased prothrombin activity and reduced total protein concentration in ascitic fluid. When these five variables were introduced in a multivariate analysis, only the ascitic fluid protein concentration was found to correlate independently with spontaneous bacterial peritonitis development (p = 0.002). The probability of first spontaneous bacterial peritonitis after 3 yr of follow-up was 24% and 4% in patients with ascitic fluid protein content lower than 1 gm/dl and greater than or equal to 1 gm/dl, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Ascites tumors in CBA mice. 2. Ultrastructural aspects on ascites conversion.

We have studied four syngeneic murine tumors, a fibrosarcoma, a squamous cell carcinoma and their two ascites-converted counterparts, by transmission electron microscopy. The ascites tumors were investigated both as cell suspensions (AA-tumor) and as solid tumor (AS-tumor). We have also studied the ascites tumors, enzymatically produced cell suspensions of the AS-tumors and solid original tumors by scanning electron microscopy. The two ascites tumors are totally de-differentiated and lack intercellular junctions. This, we think, is a prerequisite for ascites growth. But the ascites tumors show no peculiar ultrastructural features in comparison with other undifferentiated malignant tumors. We found no morphological cell alternations by the enzymatical dissociation procedure used to bring the solid tumors into suspension. Differences between the AS and AA tumors can be ascribed to differences in proliferation rates.

Animals

Tense ascites redefined: renal consequences of tense ascites in decompensated cirrhotics.

Cirrhotics with tense ascites fail to achieve increased diuresis in the supine position. To assess the role of inferior vena cava compression in this phenomenon, we studied cirrhotics with mild to moderate (n = 11) and tense (n = 2) ascites, and patients with membranous inferior vena cava obstruction (n = 2) before and after balloon dilatation, in the sitting, supine and 10 degrees head down tilted positions for 2 hours each. Urinary output (p < 0.005), creatinine clearance (p < 0.025) and sodium excretion (p < 0.025) increased in cirrhotics with mild to moderate ascites in the supine position, and further in the head down position. Similar changes occurred in patients with inferior vena cava membrane. In cirrhotics with tense ascites, these parameters did not change significantly in the supine position, but increased in the head down position. We conclude that failure to augment diuresis in the supine position in cirrhotics with tense ascites is not due to inferior vena cava obstruction alone but is probably also due to compression of the collateral vessels. This clinical observation may serve as a criterion for diagnosing tense ascites.

Ascites

Treatment of resistant ascites by continuous ultrafiltration--reinfusion of ascitic fluid.

Eight patients with diuretic-resistant ascites due to cirrhosis were treated by reinfusion of concentrated ascitic fluid. In 11 procedures, with a mean duration of 21.9 hours, weight loss averaged 14.8 kg. Complications during reinfusion included septicemia in 1 procedure, left-sided heart failure in 5, pyrexia in 7 and coagulation abnormalities in 10. Ascites recurred within 2 months after reinfusion in all but one patient. Although this technique is an efficient and inexpensive method of treatment of ascites, it does not appear indicated in patients with cirrhosis and resistant ascites in view of the possibly serious complications associated with reinfusion and the poor long-term results.

Aged

Treatment of intractable ascites by continuous reinfusion of the sterilized, cell-free and concentrated ascitic fluid.

The new method for continuous reinfusion of sterilized, cell-free and concentrated ascitic fluid is described, and utilized in 72 patients with intractable ascites in both malignancy as well as liver cirrhosis and is described with satisfactory results. The management by repeated ascites reinfusion of patients with benign massive ascites has been possible. This method is capable of being applied to patients with malignant ascites. Symptomatic relief and prolonged survival time is anticipated. The method described in this study is simple and free of adverse effects.

Adult