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[Differentiation of malignant and non-malignant origin of ascites by determination of levels of cholesterol and lactate dehydrogenase in ascitic fluid is not absolute].

The authors Castaldo et al. (Clin. Chem., 1994, 30: 478-83) state, that the ascitic lactate dehydrogenase and ascitic cholesterol association correctly identified 100% of malignant ascites from ascites associated with cirrhosis and/or hepatocellular carcinoma, with help of stepwise multiple linear discriminant analysis. The free software Capsules--Ascites is via internet available (http:¿www.leeds.ac.uk/acb), which use the mathematical formula from this article. As we argue, Castaldo's state is not correct. Three independent multidimensional statistical methods--bivariate reference regions (program EVAL-KIT), cluster analysis (program BioAnalyst), geometrical distance classification (program GEODICLA) applicated on Castaldo's original data showed that lactate dehydrogenase and cholesterol have not satisfactory absolute discriminative power between malignant from nonmalignant ascites in general, but the probability to determinate the right diagnosis is about 91-93%. Research conducted in correctly selected probands should provide information which is valid not only for the selected sample but for the entire population, to achieve more generally valid conclusions, useful for practical decisions. In addition, in the compiled table show we sensitivity and specificity of different laboratory parameters publicated in 11 original articles in the nineties, all with diagnostic efficiency less 100%.

Ascites↗

New method of extracorporeal concentration of ascitic fluid as a treatment of refractory ascites.

A new piece of equipment for the treatment of ascites is described. Ascitic fluid is drained by gravity in a unit consisting of an Amicon D-30 ultrafilter and a bag used as transit reservoir placed below the patient. When the bag is full, it is raised to a height sufficient to let the fluid flow back through the filter to the peritoneal cavity. Mainly during this step ultrafiltration of ascitic fluid occurs through the membrane of the filter. Ultrafiltration is enhanced by the negative pressure created in the filtrate compartment due to the height difference between filter unit and filtrate drainage bag placed at the bottom of the machine. Proteins in the ascitic fluid are retained and returned to the abdominal cavity. The machine cycle is automatically repeated as many times as necessary to achieve the scheduled patient weight loss. 17 patients have been treated for a total of 1.94 sessions/patient with reinfusion of the fluid in the abdominal cavity. In all patients a significant reduction of the amount of ascitic fluid and of its rate of formation have been achieved. The treatment was well tolerated and no side effects were observed. After treatment the diuresis and the sodium excretion increased significantly in all patients. The system is safe and reliable for the treatment of refractory ascites without major complications.

Adult↗

Value of ascitic fluid ferritin in the differential diagnosis of malignant ascites.

The ascitic fluid ferritin concentrations were compared with serum-ascites albumin gradient (SAAG), in their diagnostic ability for detection of malignancy in 60 patients with ascites: 29 with chronic liver disease alone (CLD) and 31 patients with various neoplasms. Of the patients with malignancy, 12 had liver metastases, 9 had no evidence of liver involvement, and 10 had hepatocellular carcinoma (HCC) with or without coexisting liver cirrhosis. Analysis of our data confirms that the ascitic ferritin is a more accurate indicator of malignant ascites (MA) than the SAAG. This new parameter is particularly helpful in distinguishing MA associated with HCC and/or metastatic liver disease from nonmalignant ascites due to CLD alone.

Ascites↗

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↗

Proteases and antiproteases related to the coagulation system in plasma and ascites. Prediction of coagulation disorder in ascites retransfusion.

To improve the ability to predict the occurrence of coagulation disorders in ascites retransfusion and, in addition, to better define the nature of the coagulation disorder, several proteases and antiproteases were analyzed in ascites and plasma before ascites retransfusion in 17 patients. Plasminogen, alpha 2-antiplasmin, antithrombin III, and fibrin(ogen) degradation products in ascites were significantly altered in patients who later developed abnormal coagulation as compared to those who did not. Only plasminogen and alpha 2-antiplasmin in ascites achieved a sufficient predictive value for the occurrence of coagulation abnormalities. The pattern of the coagulation abnormalities observed strongly suggests fibrinolysis induced by the infusion of plasminogen activators as the cause of the coagulation disorder in ascites retransfusion procedures.

Antithrombin III↗

A patient with myelofibrosis complicated by refractory ascites and portal hypertension: to tips or not to tips? A case report with discussion of the mechanism of ascites formation.

In patients with myelofibrosis, clinically significant portal hypertension is known to be predominantly presinusoidal; however, the exact mechanisms are still controversial. The pathophysiology is particularly enigmatic in those patients without histological and angiographic evidence of significant intra- or extrahepatic obstruction to portal blood flow, respectively. Moreover, ascites formation has been reported in such cases, but in general is rare in presinusoidal portal hypertension. Here we present such a patient in which ascites developed even in the presence of unchanged serum protein levels (oncotic pressure) and was refractory to sodium restricted diet and high-dose diuretic treatment. A discussion on the parameters influencing fluid exchange and ascites formation particularly emphasizing the potential importance of the hyperdynamic circulation in this case is given. Finally, the patient was treated by implanting a transjugular intrahepatic shunt (TIPS), exerting a diuretic effect sufficient enough to avoid re-formation of ascites for several months. However, ascites re-accumulated potentially due to the appearance of ectopic peritoneal myeloid metaplasia and the patient died soon afterwards. In conclusion, TIPS may be considered as rescue management for refractory ascites secondary to portal hypertension, but caution in respect to the presence and/or development of peritoneal or other ectopic haematopoesis has to be taken.

Aged↗

Fibrinolytic study in plasma and ascitic fluid of cirrhotic patients before and after ascites concentration; reinfusion technique.

Management of cirrhosis with massive ascites involves particular difficulties. The introduction of a peritoneovenous shunt and reinfusion of concentrated ascitic fluid techniques allows increased diuresis and improves renal function. However, these procedures have frequently been associated with disseminated intravascular coagulation and/or activation of fibrinolysis. Factor VIII activity, antigen and ristocetin cofactor, plasminogen, antiplasmin, plasminogen activator activity and plasmin-antiplasmin complex were investigated both in the ascitic fluid and plasma of cirrhotic patients before and after the concentration-reinfusion technique. Our results indicated that no hyperfibrinolysis was seen in the plasma of cirrhotic patients and that activation of fibrinolysis exists in ascites. Significantly higher levels of plasmin-antiplasmin complex and plasminogen activator activity were found in ascitic fluid than in plasma. In post-reinfusion much higher levels of all three Factor VIII components were observed in cirrhotic plasma than in normal plasma. In conclusion, activation of fibrinolysis could explain coagulation complications occurring after ascites reinfusion. Antifibrinolytic treatment could render the concentration-reinfusion technique more acceptable.

Adult↗

Effects of ascites resolution after successful TIPS on nutrition in cirrhotic patients with refractory ascites.

OBJECTIVE: Malnutrition is common in patients with decompensated cirrhosis and refractory ascites. The use of transjugular intrahepatic portosystemic stent shunt (TIPS) is effective in eliminating ascites. The purpose of this study was to investigate the effect of TIPS and resolution of refractory ascites on the nutritional status of patients with decompensated cirrhosis. METHODS: Fourteen consecutive patients with refractory ascites and a Pugh score of 9.0+/-0.5 had a TIPS insertion. Biochemical data, resting energy expenditure (REE), total body nitrogen (TBN), body potassium (TBK), body fat (TBF), muscle force (MF), and food intake were recorded before TIPS, and at 3 and 12 months after the procedure. RESULTS: Ten patients completed the study. Baseline values for REE, TBN, TBF, MF, and energy intake were below normal at baseline. There was a significant increase in dry weight, TBN, and REE at 3 and 12 months compared with baseline. TBF improved significantly at 12 months. There was a trend toward an increase in energy intake (p = 0.072). There was no change in protein intake, TBK, MF, and Pugh score. CONCLUSION: In cirrhotic patients with refractory ascites, resolution of the ascites after TIPS placement resulted in improvement of several nutritional parameters, especially for body composition.

Absorptiometry, Photon↗

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↗

[Treatment of cancer ascites by combined intraperitoneal administration of low-dose CDDP and reinfusion of ultra-filtrated and concentrated ascitic fluid in patients].

Ascites due to carcinomatous dissemination is a severe problem for end-stage cancer patients. We attempted treating patients on an outpatient basis with the administration of low-dose CDDP-i.p. and reinfusion of ultrafiltrated and concentrated ascites. From 1995, we performed this therapy on 16 patients with concentrated ascites 6-8 fold and reinfusion, combined with low-dose CDDP-i.p. and drip infusion of 5-FU intravenously. The ascitic fluid was significantly decreased after treatment in 8 patients, and 2 patients had lasting low concentrations of CA 125. CA 125 decreased in 83.3% of patients, who tended to have extended survival times after remarkable ascites pooling and treatment with low-dose CDDP-i.p. and reinfusion therapy. This treatment is a useful cant method for decreasing ascites and improving QOL.

Adult↗

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↗

Establishment of a human ovarian cancer cell line capable of forming ascites in nude mice and effects of tranexamic acid on cell proliferation and ascites formation.

The present study was designed to obtain an experimental tumor model as similar as possible to human ovarian cancer which often had a large amount of ascites and to assess the therapeutic value of tranexamic acid. Human tumor cell lines which form ascites in nude mice were established from ascites of patient with serous cystadenocarcinoma of the ovary. Two cloned cell lines designated HRA and HR-1 were obtained from the parent cell line designated HR. All of these cultured cell lines had about 2.5-3.5 times higher lactate dehydrogenase activities than the original tumor. The original tumor and the tumor grown in nude mice had all 5 bands of lactate dehydrogenase isoenzymes, while all cultured cell lines had only a marked lactate dehydrogenase-3 in addition to a faint lactate dehydrogenase-2. Modal chromosome numbers of HR cells ranged from 50-76, while that of HRA cells ranged widely from 40-140. The DNA histograms of HR and HRA cells were similar to each other, showing predominant G1 and S phases. Although these cell lines had ability to produce ascites in the nude mice when the cells were inoculated i.p., the HRA cell inoculation made ascites most rapidly and brought about the shortest median survival (39 days). The proliferations of all three cell lines were dose-dependently inhibited by tranexamic acid. However, the concentration of this drug required for 50% inhibition of the proliferation of HRA cells was about one-half of that of HR and HR-1 cells. In addition, i.p. injections of tranexamic acid to nude mice treated with cisplatin resulted in a significant inhibition of the ascites formation and prolongation of 50% survival.

Animals↗

Value of ascitic fibronectin and cholesterol concentration in the differentiation between malignancy-related and non-malignant ascites.

In this prospective study, we tried to evaluate various "humoral tests of malignancy" regarding their efficiency of discriminating between malignancy-related and non-malignant ascites. Fibronectin, total protein, number of cells, LDH, pH, specific gravity and cytology were compared in the ascitic fluid of 51 patients with malignancy-related and 52 patients with non-malignant ascites; patients with tuberculous peritonitis were not included. Ascitic fluid cholesterol was determined in 36 of 51 malignancy-related and in 37 of 52 non-malignant ascites. Cytology and fibronectin were found 100% specific with diagnostic efficiency 87.5% and 94.2% respectively under optimal conditions. Cholesterol was neither sensitive nor specific. It is concluded that fibronectin was a valuable test for malignancy-associated ascites.

Ascitic Fluid↗

The circulation of ascitic fluid; interchange of plasma and ascitic fluid protein as studied by means of C14-labeled lysine in dogs with constriction of the vena cava.

After plasma containing labeled plasma protein has been given intraperitoneally to dogs with experimental ascites a steady and rather rapid movement takes place of the labeled protein into the circulating blood. When plasma containing labeled plasma protein has been injected intravenously into the ascitic dog the labeled protein steadily disappears from the circulating blood and appears promptly and steadily in the ascitic fluid. The period of complete exchange or turnover in either instance is measured in days (2 to 7), but many factors enter in and make for variation. Lysine labeled with radio carbon is incorporated into the plasma proteins by feeding the donor dog. These experiments emphasize the ready exchange of proteins in the plasma with those in the ascitic pool and vice versa. This exchange may be termed circulation of ascitic protein.

Animals↗

Expression of vascular endothelial growth factor and E-cadherin in human ovarian cancer: association with ascites fluid accumulation and peritoneal dissemination in mouse ascites model.

Ascites formation and peritoneal dissemination are critical problems in patients with advanced ovarian cancer. Vascular endothelial growth factor (VEGF), also known as angiogenic growth factor, is a potent mediator of peritoneal fluid accumulation and angiogenesis of tumors. E-Cadherin is an adhesion molecule that is important for cell-to-cell interaction. To elucidate the molecular mechanism of ascites formation and peritoneal dissemination of ovarian cancer, we examined the expression of VEGF and E-cadherin in different ovarian cancer cell lines and utilized nude mice to compare the biological characteristics of ovarian cancer cells. Three human ovarian cancer cell lines (AMOC-2, HNOA and HTBOA) were used in this study. Expression of genes was analyzed by northern blotting and RT-PCR methods. AMOC-2 expressed E-cadherin, but not VEGF. HNOA expressed VEGF without E-cadherin expression. HTBOA expressed both VEGF and E-cadherin. Each human ovarian cancer model revealed a specific feature. The AMOC-2 mouse had a single large peritoneal tumor without ascites or remarkable peritoneal dissemination. HTBOA and HNOA mice had bloody ascites and marked peritoneal dissemination. Introduction of VEGF antisense into HTBOA cells could inhibit the ascites formation. It is suggested that VEGF is important for the ascites formation via the increased vascular permeability effect. The deregulation of E-cadherin expression might be involved in the peritoneal dissemination. These molecules are important for the formation of specific features of advanced ovarian cancer. Ovarian cancer cell lines that had different gene expression patterns produced nude mouse human ovarian cancer models with different characteristics.

Animals↗

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↗