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[Peritoneovenous diversion using the LeVeen shunt in the treatment of refractory ascites after liver transplantation].

Intractable ascites is a rare complication after liver transplantation. In this study, the authors report 2 cases of intractable ascites after liver transplantation. The authors discuss the etiology of ascites and the place of peritoneovenous shunt as a therapeutic option. From 1985 to 1996, 354 liver transplantations were performed. In two cases, liver transplantation was performed for post-VHC liver cirrhosis and giant hemangioma. Both patients developed intractable ascites and were successfully treated by peritoneovenous shunt. The etiologies of ascites after liver transplantations are multiple: mechanical after vascular complication; lymphatic leak after surgical dissection; metabolic disorder; intrahepatic lesion of the graft. In our cases, the etiology of ascites was intrahepatic lesion of the graft due to VHC infection in the first case and acute rejection in the second. Peritoneovenous shunt is a therapeutic option for the treatment of intractable ascites after liver transplantation. Its indication should be considered only for isolated intractable ascites without portal hypertension and without liver cell failure after liver transplantation.

Acute Disease↗

Selective intestinal decontamination with norfloxacin reduces bacterial translocation in ascitic cirrhotic rats exposed to hemorrhagic shock.

Bacterial translocation (BT) can be involved in the pathogenesis of severe infections due to bacteria of enteric origin that complicates bleeding cirrhotic patients. To assess the effect of hemorrhagic shock (HS) on the incidence of BT and if selective intestinal decontamination (SID) reduces this incidence, we studied six groups of Sprague-Dawley rats: ascitic rats, ascitic rats exposed to HS with and without previous norfloxacin prophylaxis, healthy rats, and healthy shocked rats with and without previous norfloxacin prophylaxis. BT tended to be higher in ascitic rats with shock than without shock (69% vs. 41%, P = .15) and was significantly higher in healthy rats with than without shock (50 percent vs. 0 percent, P = .01). Norfloxacin significantly reduced translocation in ascitic shocked rats in comparison with nondecontaminated ascitic shocked rats (31 percent vs. 69 percent, P = .038). This effect was due mainly to a reduction of gram-negative BT (O percent vs. 37 percent, P = .008). In addition, norfloxacin prevented translocation in healthy shocked rats. Accordingly, aerobic gram-negative bacteria disappeared from fecal flora in all rats administered norfloxacin, except for Klebsiella species in one control rat. Cecal severe submucosal edema, chronic inflammatory infiltrate, and intestinal lymphangiectasia were significantly more frequent in ascitic rats than in control rats. Intestinal mucosal injury related with HS, particularly subepithelial cecal edema, was observed only in ascitic shocked rats. In conclusion, HS increases the incidence of BT both in ascitic cirrhotic and healthy rats. Norfloxacin reduces significantly the incidence of translocation after shock, especially in those cases caused by aerobic gram-negative bacilli.

Animals↗

Molecular species of glycerolipids of Ehrlich ascites cells and of their fat granules.

Ehrlich ascites cells were grown in mice and were isolated by centrifugation of the ascites fluid. The cells were lysed with distilled water, and the floating fat particles were collected by centrifugation. The particles contained about 90% neutral and 10% polar lipid. The neutral lipid was made up of about 50% triacylglycerol, 30% alkyldiacylglycerol, 3% cholesteryl esters, 3% free cholesterol and 4% free diacylglycerols. The phospholipid fraction was comprised of about 50% phosphatidylcholine, 35% phosphatidylethanolamine, 10% sphingomyelin and small amounts (less than 5% total) of serine and/or inositol phosphatides. The triacylglycerol and alkyldiacylglycerol fractions possessed total carbon number and fatty acid compositions closely similar to those reported in the literature for whole ascites cells and for a cell membrane preparation. Likewise, the fatty acid composition of phospholipids from the granules in general was similar to that reported for Ehrlich ascites cells. On the basis of the polar and neutral lipid ratio, the lipid granules of the ascites cells were calculated to possess lipid core diameters of 30-50 nm, which were 40-70 times smaller than those (up to 2 mu) measured for the lipid granules of the intact cells by electron microscopy. The characterization of the lipid composition of the Ehrlich ascites lipid granules was completed by determining the molecular species composition of the diacyl, alkylacyl and alkenylacyl phosphatidylethanolamines and of the diacyl and alkylacyl phosphatidylcholines of the ascites cells. It is concluded that the alkyldiacylglycerols of the Ehrlich ascites cells occur largely in the cytoplasmic lipid granules, which appear to consist of many particles of the size and structure of very low density lipoproteins enclosed in membranous sacs.

Animals↗

[Management of malignant ascites by intraperitoneal injection of OK-432. Possible mechanism of the reduction of original tumor mass volume].

We studied the effect of intraperitoneal injection of OK-432 on the growth of original tumor mass in patients with malignant ascites and a possible mechanism of reduction of tumor volume. Sixteen patients with valuable original tumor mass and a large amount of ascites caused by gastro-intestinal cancer were studied. Tumor cells were separated from ascitic fluids and cultured in vitro before the study. Lymphocytes were collected from the fluids at varying intervals after intraperitoneal injection of OK-432 and cultured 24 hours in vitro. Effect of the culture supernatant on ascites-derived autologous tumor cell growth was examined in vitro using microplate assay. The results were as follows. 1) Reduction of tumor mass more than four weeks was found in 4 of 16 cases. 2) Before OK-432 injection, the culture supernatant from ascites-derived lymphocytes did not inhibit autotumor cell growth in vitro. But, the supernatant from lymphocytes which were collected from the ascites after OK-432 injection markedly inhibited tumor growth in all of 4 tumor mass reduction cases. In 12 non-reduction cases the supernatant slightly inhibited tumor growth only in 2 cases. 3) A similar growth inhibitory factor was detected in the mixed culture-supernatant of peripheral blood lymphocytes and OK-432 in vitro. 4) Preliminary studies indicated that the tumor growth inhibitory factor might be different from tumor necrosis factor and interferons. These results indicate that ascites-derived lymphocytes-producing factor may play an important role in reduction of tumor mass volume in patients with cancerous ascites.

Adenocarcinoma↗

Further studies on the relationship between allotransplantability and the presence of the cell surface glycoprotein epiglycanin in the TA3-MM mouse mammary carcinoma ascites cell.

The loss of strain specificity in the TA3-St mammary carcinoma ascites cell during passage in ascites form in diseased syngeneic strain A mice was confirmed by the observation that TA3-MM/2 ascites cells were capable of progressive growth in 7 foreign mouse strains. Support for the hypothesis that allotransplantability in the TA3-MM lines may be due to masking of cell surface histocompatibility H-2a antigens by large glycoprotein (epiglycanin) molecules was obtained from the finding that the capacity of the TA3-MM/2 ascites cell to absorb anti-H-2a antibody was several times less than that of the parent TA3-St ascites cell, although it was greater than the capacity of the non-strain-specific TA3-Ha line. Further support for the location of epiglycanin molecules at the cell surface was obtained by transmission electron-microscopic observation of a high concentration of filamentous structures, usually 20-40 nm long, but often extending to 200-300 nm length at the TA3-MM/2 cell surface. Similar structures were also observed at the TA3-Ha cell surface but were not observed at the surface of the TA3-St ascites cell, a cell known to contain no detectable epiglycanin. Epiglycanin molecules, obtained by two different methods from TA3-MM/1, TA3-MM/2, and TA3-Ha ascites cells, were shown to be similar with respect to their capacities to inhibit the binding of 125I-labeled epiglycanin to its antibody, induced in the rabbit by TA3-Ha ascites cells in a radioimmunoassay.

Animals↗

Ascitic fluid alpha 1-antitrypsin.

Ascitic fluid alpha 1-antitrypsin (AF-AAT) was compared with ascitic fluid total protein (AF-TP) and the serum-ascites albumin gradient (SAAG) in the differential diagnosis of ascites. The study included 82 consecutive patients of which 42 had cirrhosis, 8 hepatoma (with cirrhosis), and 27 malignant ascites (peritoneal 18, liver 9). The concentration of AF-AAT (milligrams per deciliter) was significantly elevated (P less than 0.001) in hepatoma (174 +/- 123), malignant liver disease (232 +/- 119) and peritoneal neoplasms (376 +/- 106) in comparison with cirrhotics (66 +/- 33). In separating ascites caused by cirrhosis or malignancy, AF-AAT (discriminating limit of 120 mg/dl) had a 96% sensitivity, 95% specificity, and 96% diagnostic efficacy, which was superior to the 87% observed for AF-TP and 86% for the SAAG. Similar results were obtained for the A/S AAT ratio but this test was not available in all patients. AF-AAT was particularly useful in patients with malignancy causing portal hypertension as assessed by SAAG (hepatoma, malignant liver disease). We conclude that AF-AAT may be a valuable parameter in the differential diagnosis of ascites.

Ascites↗

Temporary use of peritoneovenous shunting for treatment of tense ascites following a Whipple procedure.

Tense, nonchylous ascites following a Whipple procedure has not been reported to date. We describe the course of such a patient successfully treated by a peritoneovenous shunt. A 49-year-old male developed tense ascites following pancreaticoduodenectomy. Despite conservative measures, abdominal distension developed to the point of dyspnea and orthopnea for over a six-month period. Because the physicochemical characteristic of the ascitic fluid was consistent with that of hepatic lymph, ascites was considered due to injury to the lymphatics around the porta hepatis. A peritoneovenous shunt was established for the treatment of ascites and was removed when the ascites had resolved at nine months after shunting. Our experience suggests that, in case conservative measures fail in the control of ascites, either direct repair of the lymphatic leak by laparotomy or the temporary use of peritoneovenous shunting may be considered.

Ascites↗

Involvement of VEGF and its receptors in ascites tumor formation.

Vascular endothelial growth factor (VEGF) has potent endothelial cell mitotic and vascular permeability activity. Several reports have suggested that VEGF may be one of the major factors regulating ascites formation, although no quantitative and systematic analyses have been carried out. To determine the role of VEGF in ascites formation, we examined the expression of VEGF in 13 mouse ascites tumors (5 sarcomas, 3 carcinomas, and 5 hematopoietic malignancies). We found that significant amounts (6-850 ng/mL) of biologically active VEGF accumulated in the ascites fluid of all 13 tumors, particularly in tumors of sarcoma and carcinoma origin (430 +/- 234 ng/mL). The microvessel densities in the peritoneal walls of tumor-bearing mice, which are significantly higher than those in healthy mice, basically correlated with but did not parallel VEGF concentrations, suggesting the existence of an additional modulator(s) of the angiogenic process. Administration of anti-mouse VEGF-neutralizing antibody to mice bearing the carcinoma-derived ascites tumor MM2 suppressed ascites accumulation, tumor growth, and tendency to bleed. These results directly demonstrate the crucial role of VEGF in carcinoma-derived ascites tumor formation in vivo.

Animals↗

The role of laparoscopy in the evaluation of ascites of unknown origin.

The role of laparoscopy in the diagnostic evaluation of ascites of unknown origin was studied in 129 patients. Laparoscopic results were as follows: (1) Carcinomatosis peritonei in 78 (60.5%). Peritoneal biopsies in 76 of these cases revealed malignancy in 67 (adenocarcinoma 62, lymphoma 4, mesothelioma 1) and tuberculosis in 5; specimens were inadequate for diagnosis in 4. (2) Tuberculous peritonitis in 26 (20.2%). Peritoneal biopsies in 24 of these cases revealed tuberculosis in 22 and non-specific chronic peritonitis in 2. (3) Cirrhosis in 7 (5.4%). (4) No gross abnormality in 18 (14.0%). Of the latter, causes of ascites had already been identified in 13 (72.2%), including chronic renal failure in 7, systemic lupus erythematosus in 2, constrictive pericarditis in 2, chronic pancreatitis with chylous ascites in 1, and retroperitoneal lymph node metastasis with chylous ascites in 1. Thus, laparoscopic observation in combination with biopsy established the cause of ascites of unknown origin in 111 (86.0%) of 129 patients. Most of the 18 patients without gross laparoscopic abnormality had underlying disease identified as a cause of ascites; laparoscopy was indicated in these cases to exclude other processes that may also cause ascites.

Adult↗

Paracentesis in the management of cirrhotic ascites.

During the last few years, several studies including six randomised, controlled trials reevaluating therapeutic paracentesis in the management of cirrhotic patients with tense ascites have been reported. The main findings of these investigations are: (i) Repeated large-volume paracentesis (evacuation of 4-6 l/day until complete mobilization of ascites) or total paracentesis (complete mobilization of ascites in only one tap) associated with i.v. albumin infusion (6-8 g/l of ascitic fluid removed) are more effective in eliminating the intra-abdominal fluid than conventional diuretic therapy, are associated with a lower incidence of complications and considerably reduce the duration of hospital stay and the cost of treatment; (ii) The mobilization of ascites by paracentesis without albumin infusion is associated with an impairment in effective circulating blood volume, as indicated by a decrease in cardiac output, central venous pressure, pulmonary capillary wedge pressure and plasma concentration of atrial natriuretic peptide and a marked elevation of plasma renin activity and aldosterone concentration. In 20% of patients this circulatory disturbance is accompanied by the development of renal impairment and/or dilutional hyponatraemia. These changes can be detected within the first 24 h following complete mobilization of ascites and do not occur when plasma volume is expanded with albumin; (iii) Hemaccel and dextran 70 appear to be as effective as albumin in preventing renal and electrolyte complications after paracentesis; (iv) Therapeutic paracentesis is an alternative treatment to peritoneovenous shunting in cirrhotic patients with refractory ascites.

Ascites↗

A clinical view of recent advances in ascites.

We discuss current perspectives in ascites, focusing on newer developments of interest to clinicians and stressing the value and limitations of therapeutic paracentesis. Because there is considerable evidence to support both the "underfilled" and "overflow" hypotheses for the development of ascites, current concepts concentrate on integration of these two theories. In the management of ascites the rate of ascites mobilization is more important than the method by which excess peritoneal fluid is removed; thus salt restriction may not have to be rigid if diuretics are used judiciously. An approach to intractable ascites emphasizes the difference between unresponsive and refractory ascites, but in both situations a conservative philosophy is recommended. Nonhepatic causes of ascites are briefly reviewed since their management may require principles different from those used in cirrhosis.

Animals↗

Mechanisms of early decrease in systemic vascular resistance after total paracentesis: influence of flow rate of ascites extraction.

BACKGROUND: An early decrease in systemic vascular resistance (SVR) after total paracentesis has been observed in ascitic patients who developed paracentesis-induced circulatory dysfunction. AIMS: To investigate the mechanisms of early changes in SVR after total paracentesis and the influence of intra-abdominal pressure and the flow rate of ascites extraction on the development of an early decrease in SVR. METHODS: Twenty-two cirrhotic patients with tense ascites were treated by total paracentesis (7 +/- 0.4 l). Measurements of intra-abdominal pressure and the volume of ascites removed were recorded every 10 min. Hormonal and haemodynamic measurements were performed at baseline and 3 h after total paracentesis. RESULTS: SVR decreased 3 h after paracentesis in 17 patients and remained stable in five patients. Patients with a decrease in SVR showed a significant increase in nitrite/nitrate serum values (4.4 +/- 0.9 to 7.4 +/- 1 nmol/ml; P < 0.05). A significant correlation was observed between the decrease in SVR and nitrite/nitrate serum values (r = 0.566; P < 0.05). The volume of ascites removed was similar in patients with and without a decrease in SVR. Patients with a decrease in SVR showed higher baseline intra-abdominal pressure, shorter duration of paracentesis (60 +/- 4.9 vs 88 +/- 0.4 min; P < 0.01) and higher flow rate of ascites extraction (1.18 +/- 0.08 vs 0.81 +/- 0.12 l/min; P < 0.05). CONCLUSIONS: Our results confirm that an early decrease in SVR after total paracentesis is due to an increase in arterial vasodilation that may be related to an abrupt decrease in intra-abdominal pressure after fast paracentesis. Haemodynamic disturbances after total paracentesis could be prevented by reducing the flow rate of ascites extraction.

Abdomen↗

Study of hepatic venous wedge and intraperitoneal pressures in cirrhotic patients with refractory ascites treated by dialytic ultrafiltration.

Three cirrhotic patients with intractable ascites and one patient with malignant ascites received dialytic ultrafiltration of ascitic fluid by a haemofilter system for symptomatic relief. The haemofilter removes fluid and substances with a molecular weight less than 50,000 daltons and the concentrated ascitic fluid was reinfused into the peritoneal cavity after ultrafiltration. The changes in intraperitoneal and hepatic venous wedge pressures were studied in these patients. Dialytic ultrafiltration of ascites was associated with a parallel fall of both intraperitoneal and hepatic venous wedge pressures in cirrhotic patients but not in the patient with malignant ascites. The intraperitoneal and hepatic venous wedge pressure remained low for 18 h after completion of dialytic ultrafiltration. The mean arterial pressure and central venous pressure remained unchanged despite rapid removal of ascitic fluid. The interrelationships between the intraperitoneal pressure, hepatic venous wedge pressure, and vascular volume are discussed.

Adult↗

Unsuspected infection is infrequent in asymptomatic outpatients with refractory ascites undergoing therapeutic paracentesis.

OBJECTIVE: Large-volume paracentesis is a safe and effective means of treating patients with refractory ascites. However, there is limited information regarding the need for ascitic fluid studies in asymptomatic outpatients presenting for therapeutic paracentesis. The aim of this prospective study was to define the incidence and natural history of peritoneal fluid infection in asymptomatic outpatients undergoing therapeutic paracentesis. METHODS: Over a 13-month period, 118 therapeutic paracenteses were performed in 29 outpatients with decompensated cirrhosis (Child-Pugh class B = 38%, C = 62%). After a brief medical history and physical examination, ascitic fluid cell count with differential and culture were obtained from all participating subjects. Seven (24%) of the subjects were receiving norfloxacin prophylaxis, accounting for antibiotic coverage during 40% of the procedures performed. The clinical course and outcome of study subjects during a mean follow-up of 137 days was reviewed. RESULTS: All 118 (100%) of the ascitic fluid samples demonstrated absolute neutrophil counts of <250/mm3 (mean = 6.5 +/- 22.5 pmn/mm3). Asymptomatic bacterascites was identified from three of the 118 (2.5%) fluid samples, but all of these subjects spontaneously recovered without treatment or sequelae. During follow-up, six episodes of symptomatic or hospital-associated peritoneal fluid infection were identified in study participants, emphasizing the importance of fluid studies in other clinical settings. CONCLUSIONS: Although further studies are needed, the routine culture of ascitic fluid in asymptomatic outpatients with refractory ascites requiring therapeutic paracentesis may not be necessary when there is a low index of suspicion for occult infection. In circumstances of clinical uncertainty, however, obtaining ascitic fluid cell counts with differential is recommended to insure patient safety.

Adult↗

Ascitic fluid concentrations of fibronectin and cholesterol: comparison of differential diagnostic value with the conventional protein determination.

Ascitic fluid concentrations of fibronectin, cholesterol and protein were determined in 95 patients: 38 with cirrhosis of the liver, 10 with miscellaneous nonmalignant diseases, 43 with peritoneal carcinomatosis and 4 with liver metastases or hepatocellular carcinoma. Fibronectin, cholesterol and protein at discrimination values of 7.5 mg/100 ml, 45 mg/100 ml and 3.0 g/100 ml, respectively, separated patients with peritoneal carcinomatosis from patients with cirrhosis with an efficiency of 94%, 90% and 85%, respectively. Thus, ascitic fluid determinations of fibronectin and cholesterol offer good discrimination of cirrhotic ascites from ascites related to peritoneal carcinomatosis, superior to the conventional protein determination. However, the failure of all parameters to distinguish ascites caused by miscellaneous nonmalignant diseases from malignancy-related ascites underscores the importance of highly specific methods to confirm a suspected diagnosis of malignancy-related ascites.

Ascites↗

High interleukin-6 production within the peritoneal cavity in decompensated cirrhosis and malignancy-related ascites.

To assess the diagnostic and prognostic value of interleukin-6, interleukin 1 beta, and tumor necrosis factor-alpha assays in plasma and ascites, we measured these cytokines in eight patients with malignancy-related ascites and 32 patients with decompensated cirrhosis. Five patients had an episode of bacterial peritonitis, during which one or more ascitic fluid samples were analyzed. Interleukin-6 and tumor necrosis factor-alpha were not significantly different between the cirrhotic and the malignant groups: ascitic interleukin-6 13,816 +/- 15,314 vs 28,138 +/- 23,403 pg/ml, plasma interleukin-6 542 +/- 719 vs 559 +/- 604 pg/ml; ascitic tumor necrosis factor-alpha 19 +/- 50 vs 12 +/- 31 pg/ml, plasma tumor necrosis factor-alpha 3.4 +/- 8.2 vs 6.1 +/- 13.8 pg/ml. During an episode of bacterial peritonitis there was a significant increase only in ascitic interleukin-6 (133,268 +/- 99,743 pg/ml), which declined after antibiotic treatment. None of the parameters was associated with 6-month survival (11 of the 40 patients died within 6 months). There was a correlation (r = 0.675; p = 0.002) between plasma interleukin-6 levels and the Child-Pugh score in patients with cirrhosis, but not with the etiology of the liver disorder. Plasma interleukin-6 levels correlated with IgA levels (r = 0.649; p = 0.004) but not with C reactive protein, sedimentation rate, fibrinogen, IgM or IgG. These results do suggest that interleukin-6 is produced within the peritoneal cavity in hepatic and malignant ascites. There is a sharp increase in the local production of interleukin-6 during an episode of bacterial peritonitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Antibiotic penetrance of ascitic fluid in dogs.

Antibiotic concentrations in ascitic fluid after parenteral therapy may be important in the treatment of peritonitis. We have created ascites in dogs by partial ligation of the inferior vena cava. Ascitic fluid volume was measured at the time each antibiotic was administered. Nine antibiotics were studied in the same three dogs. Antibiotic concentration in ascitic fluid was found to vary inversely with ascites volume. Percentage of penetration (ratio of ascites peak to serum peak x100) ranged from 5.8 to 65% among the drugs studied. Only metronidazole showed a statistically significant higher percentage of penetration than other antimicrobials. Concentrations in ascitic fluid after single doses of cephalothin (15 mg/kg) and the aminoglycosides (2 mg/kg, gentamicin and tobramycin; 7.5 mg/kg, amikacin and kanamycin) did not exceed the minimum inhibitory concentration of many gram-negative rods and may justify the use of higher than usual initial parenteral doses, or possibly initial intraperitoneal administration in seriously ill patients.

Aminoglycosides↗

Intraperitoneal pressure in formation and reabsorption of ascites in cats.

The rate of ascites formation or reabsorption was recorded in anesthetized cats using the technique of intraperitoneal plethysmography. Hepatic venous pressure was increased using an extracorporeal circuit to drain effluent blood from the liver. When the intraperitoneal pressure was set to zero, elevation of hepatic venous pressure increased portal pressure and produced a constant rate of ascites formation. However, equivalent increments of portal pressure without elevation of hepatic venous pressure did not cause ascites formation, indicating that the liver was the source of ascites when hepatic venous pressure was increased. The rate of ascites formation was proportional to hepatic venous pressure, but elevation of the intraperitoneal pressure reduced the transsinusoidal pressure gradient responsible for fluid filtration from the liver. Although this reduced the rate of ascites formation, a secondary effect partly opposed this reduction in filtration rate. From this study and from previous work, there are now quantitative data showing that the intraperitoneal pressure is an important factor which accelerates the rate of reabsorption and decreases the rate of formation of ascites to bring these processes into equilibrium.

Animals↗