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Quality of life in refractory ascites: transjugular intrahepatic portal-systemic shunting versus medical therapy.

Uncontrolled studies suggest that transjugular intrahepatic portal-systemic shunting (TIPS) may improve quality of life in patients with refractory ascites. We hypothesized that any improvement of quality of life in patients with TIPS would be matched in controls due to the competing effects of improved ascites and worsened hepatic encephalopathy. Thus, an analysis of quality of life was performed using original data from the North American Study for the Treatment of Refractory Ascites, a multicenter trial of 109 patients randomized to TIPS or repeated large volume paracentesis (LVP) for refractory ascites. Short form 36 (SF-36) surveys were completed at baseline and at 6- and 12-month follow-up. Variables analyzed were: randomization group, number of LVP performed, cumulative volume from LVP, shortness of breath, abdominal distention, abdominal pain, diuretic usage, confusion, hospitalizations, and emergency room visits. Outcomes were changes in physical component scale (PCS) and mental component scale (MCS) of SF-36 results. We constructed multivariable, mixed effects models, including randomization group and baseline MCS and PCS. Changes in PCS and MCS from baseline were similar between the two randomization groups. In multivariate analysis, PCS improvement was associated with lack of confusion, improved ascites, and lack of hospitalizations, but not directly with randomization group. Improvement in MCS was associated with randomization to TIPS and lack of confusion. In conclusion, patients with refractory ascites randomized to TIPS or repeated LVP had similar changes in quality of life. Competing effects of hepatic encephalopathy, requirement for repeated LVP, and need for hospitalizations explain similar changes in quality of life between the two groups.

Analysis of Variance↗

Ultrasonographic determination of ascitic volume.

The purpose of this study was to develop a method by which ascitic volume can be calculated using transcorporeal ultrasonography, and to determine the accuracy of this method by comparison with the volume of distribution of a radiolabeled tracer (indicator dilution technique [IDT]). Subjects with ascites confirmed by ultrasonography were recruited from the San Francisco General Hospital Gastroenterology and Liver Clinics. With subjects in the prone position on their hands and knees, ultrasonographic measurements were obtained along the ventral surface of the abdomen. The greatest vertical depth of ascitic fluid was recorded, and the abdominal circumference was measured from this point. The ascitic fluid volume was modeled as a segment of a sphere. IDT was performed as the reference method by injecting 99mTc-labeled macroalbumin into the peritoneal cavity and determining the volume of distribution of the indicator. Nine patients were evaluated. The median volume of ascites measured by the IDT was 11.2 L (range, 1.5-17.0 L). The median volume calculated by the ultrasonographic method was 10.3 L (range, 1.2-18.0 L). The correlation coefficient between the ultrasonographic and IDT was 0.96 (P < .001). Our technique accurately determines the volume of ascites using simple ultrasonographic measurements.

Ascites↗

Utility of sonographic gallbladder wall patterns in differentiating malignant from cirrhotic ascites.

Thirty-one patients with ascites associated with malignancy and 49 patients with cirrhotic ascites were enrolled in a sonographic study of the gallbladder wall. Three gallbladder wall patterns were recognized: A, single-layered, nonthickened wall; B, single-layered, thickened wall; and C, double-layered, thickened wall. Pattern A was found more frequently in patients with malignant ascites, while patterns B and C were detected more frequently in patients with cirrhotic ascites. If "nonthickened gallbladder wall" is used as a criterion for prediction of malignant ascites, the sensitivity is 80.6% and the specificity 93.9%. This suggests that sonographic examination of the gallbladder wall is useful in the differentiation of malignant from cirrhotic ascites.

Ascites↗

Serum, pleural effusion, and ascites CA-125 levels in ovarian cancer and nonovarian benign and malignant diseases: a comparative study.

OBJECTIVES: Cancer antigen-125 (CA-125) is not a specific tumor marker and it is synthesized by normal and malignant cells of different origins. Recently it has been shown that various diseases are associated with increased CA-125 levels, especially in the presence of serosal fluid. The aim of this study is to investigate serum and fluid CA-125 levels in patients with different diseases. METHODS: A total of 133 patients and 23 healthy control cases were included in the study and divided into eight groups on the basis of disease and the presence of fluid in the serosal cavities. Serum and serosal fluid CA-125 levels were measured by a commercial enzyme immunoassay kit at the same time. Comparisons among the groups were made. RESULTS: Abnormal levels of serum CA-125 were observed in 76% of ovarian cancer patients; 96% in patients with ascites and 56% in patients without ascites. Moreover, elevated serum CA-125 levels were detected in 52% of patients with hepatic diseases, in 100% of patients with nongynecologic peritoneal carcinomatosis, and in 87% of patients with pleural effusion. Serum and fluid CA-125 levels were significantly higher in cases of ovarian cancer with ascites than in the other groups (P < 0.01). A positive correlation between serum CA-125 levels and ascites amounts was observed in cases of ovarian cancer with ascites (P < 0.01, r = 0.81). Furthermore, no correlation was observed between ovarian mass volume and serum CA-125 levels in ovarian cancer patients with stage I disease without ascites (P = 0.08, r = 0.48). CONCLUSIONS: Although CA-125 levels may be considered a sensitive tumor marker in patients with epithelial ovarian cancer, it was determined that high serum CA-125 levels were closely related to the presence of serosal fluids and serosal involvement, whatever the origin is. These results should be considered in the interpretation of CA-125 elevation in patients with ovarian cancer.

Adult↗

The influence of ascites on the pharmacokinetics of piretanide in cirrhotic patients.

The pharmacokinetics of piretanide, a new loop diuretic, were studied in seven patients with severe liver disease before and after resolution of ascites. The time to maximum concentration was significantly prolonged by the presence of ascites. Tmax after relief of ascites was similar to that seen for normal volunteers. Area under the curves, bioavailability, volumes of distribution and elimination half-lives did not change after resolution of the ascites: two patients in whom diuretic resistant ascites occurred showed similar pharmacokinetics to that of the diuretic responders. Reduced responsiveness to piretanide therapy in patients with gross ascites does not appear to be the result of decreased bioavailability.

Absorption↗

Ascites, pleural, and pericardial effusions in acute pancreatitis. A prospective study of incidence, natural history, and prognostic role.

Ascites and pleural and pericardial effusions can be observed during acute pancreatitis. The aims of this study were to evaluate their incidence, natural history, and prognostic role in patients with acute pancreatitis. One hundred patients consecutively admitted with a diagnosis of acute pancreatitis were prospectively submitted to abdominal, pleural, and cardiac ultrasonography at admission and during follow-up. Ascites was found in 18 patients, pleural effusion in 20, and pericardial effusion in 17. Twenty-four patients of this series had severe pancreatitis; three of them died. All effusions disappeared spontaneously in patients who survived pancreatitis up to two months after dismissal. At multivariate analysis ascites and pleural effusion were demonstrated to be accurate independent predictors of severity. The respective odds ratios were 5.9 [95% confidence interval (CI), 1.5-23.0%) and 8.6 (95% CI, 2.3-32.5%). Furthermore the presence of pleural effusion, ascites, and pericardial effusion were associated with an increased incidence of pseudocyst during follow-up. Ascites and pleural and pericardial effusions are frequent during acute pancreatitis. Pleural effusion and ascites are accurate predictors of severity in these patients.

Acute Disease↗

Chylous ascites following abdominal aortic surgery.

Three patients, two women, one man (mean age 74 years), who had abdominal aortic aneurysms (2) or aortobifemoral surgery (1), developed chylous ascites postoperatively. They were studied to determine their clinical course and develop a plan for management of this complication. In each patient, the ascites was not manifest until abdominal swelling developed two weeks after operation, and the problem was confirmed by the finding of milky fluid on paracentesis. A low serum albumin (mean 2.6 gm) was also characteristic. The ascites was not altered by parenteral nutrition or reduction of dietary fat and ingestion of medium chain triglycerides. In one patient (man, age 93) the ascites resolved spontaneously two months after abdominal aortic aneurysm surgery. Another (woman, age 70) was cured following operative ligation of a lymphatic fistula identified at operation five weeks after abdominal aortic aneurysm repair. In the third (woman, age 60), the ascites resolved immediately following placement of a peritoneal venous shunt six weeks after an aortobifemoral bypass. Chylous ascites is rare after aortic surgery and manifests itself about two weeks after operation, at times after discharge from hospital. It has an indolent course, but may resolve spontaneously up to two months after operation. Its course appears not to be foreshortened by diet, including omission of fat, but can be successfully treated surgically with a shunt or fistula ligation. If done early a protracted hospital course may be avoided.

Aged↗

Features of the Renin-angiotensin system in ascites and pleural effusion during severe ovarian hyperstimulation syndrome.

PURPOSE: The purpose of this work was to investigate the ovarian renin-angiotensin system (RAS) during severe ovarian hyperstimulation syndrome (OHSS) with ascites and pleural effusion. METHODS: Two patients who developed severe OHSS after ovarian stimulation for in vitro fertilization were investigated. Both patients presented ascites and pleural effusion. Blood, ascites, and pleural fluid were simultaneously sampled during therapeutic paracentesis and thoracocentesis. Renin activity, active renin, prorenin, and angiotensin II immunoreactivity (Ang II-ir) were measured simultaneously in plasma, ascites, and pleural fluid. RESULTS: Prorenin, renin activity, active renin, and Ang II-ir levels were much higher than normal plasmatic laboratory norms in the three compartments. Prorenin and Ang II-ir levels were the highest in the ascites, while they were in the same range in the pleural fluid and in the plasma. CONCLUSIONS: The present findings provide additional evidence for the ovarian origin of the prorenin and Ang II-ir in the ascites of severe OHSS.

Adult↗

Atrial natriuretic peptide in liver cirrhosis with mild ascites.

To clarify the involvement of atrial natriuretic peptide (ANP) in the pathogenesis of liver cirrhosis, we measured plasma ANP in patients with various stages of cirrhosis and in age-matched normal subjects. Urinary cyclic guanosine monophosphate (cGMP) was also measured as a marker of active biological ANP. In addition, effects of exogenous synthetic human ANP (0.5 micrograms/kg) on renal functions were examined in normal subjects and in cirrhotics without ascites or with mild ascites. Plasma ANP levels were not significantly different among these 3 groups. Urinary cGMP concentrations were significantly higher in both cirrhotics without ascites and cirrhotics with mild ascites, (340 pmol/ml, P less than 0.05 and 496 pmol/ml, P less than 0.01 respectively) than normal subjects (95 pmol/ml). In normal subjects, marked increases in urinary volume (UV), sodium excretion (UNaV), fraction excretion of sodium (FENa) and free water clearance (CH2O) were induced after ANP infusion, and significant recoveries were subsequently observed in these parameters. However, in cirrhotics, the responses to ANP infusion of UV, FENa and CH2O were far less dramatic. The response of UV, UNaV and FENa in cirrhotics with mild ascites was delayed compared to cirrhotics without ascites. These results suggest that the blunted natriuretic responsiveness to ANP is contributory to the pathogenesis of initial sodium retention in cirrhotics.

Ascites↗

Intervention for pleural effusions and ascites following liver transplantation.

BACKGROUND: Small volumes of fluid in the pleural and peritoneal cavities are common after paediatric liver transplantation. Occasionally, larger fluid collections develop and need intervention by aspiration or insertion of a drain. Objective. To assess the incidence of moderate and large pleural and peritoneal fluid collections following paediatric liver transplantation, the need for intervention and the outcome following radiological and non-radiological treatment, with the ultimate objective of recommending a treatment protocol for such post-operative fluid collections. MATERIALS AND METHODS: A total of 184 consecutive liver grafts in 164 children were reviewed. RESULTS: Of 184 grafts, 31 (16.8%) developed excessive fluid collections requiring intervention (19 pleural effusions, 8 ascites and 4 effusions and ascites). The effusions were first diagnosed between days 1 and 44 after transplant and the ascites between days 1 and 14. The initial diagnosis was made radiologically in 21 (91%) of 23 pleural effusions and in 10 (83%) of 12 ascites. No identifiable cause or association was seen in 18 (58%) of 31 cases. The mean duration of the pleural effusions and ascites, from onset of treatment to resolution, ranged from 33 +/- 42 days (SD) to 35 +/- 48 days and from 36 +/- 47 days to 39 +/- 46 days respectively. Comparison of the modes of interventional treatment (i.e. unguided, radiological and surgical) showed no statistically significant difference in the outcome of the management. CONCLUSIONS: Post-transplantation pleural effusions and ascites requiring intervention are often without definite cause. They are more common with reduced grafts, but this cannot completely explain the occurrence or the protracted duration of accumulation in spite of combined interventional management. The outcome of treatment is not significantly influenced by the mode of intervention except in cases where surgical intervention is indicated. Patients could be managed effectively without resorting to chronic outpatient aspiration. US contributed significantly in the initial and follow-up evaluation of these patients, even in cases of pleural effusions, and we would recommend greater use of US in place of radiographs to reduce the radiation burden when fluid collections are protracted.

Adolescent↗

Chronic eosinophilic ascites in a very young child.

UNLABELLED: A case of chronic eosinophilic ascites with onset in early infancy is described. An intensive diagnostic work-up ruled out other known causes of ascites in childhood. The final diagnosis was made at 2 years of age when a large number of eosinophils was detected in the ascitic fluid. The outcome was complicated by an ex vacuo intraperitoneal haemorrhage. Steroids were able to control the disease only after complete aspiration (1600 ml) of the ascitic fluid. On discontinuation of treatment, peritoneal inflammation recurred indicating steroid-dependency. CONCLUSION: eosinophilic ascites, a very rare disorder in children, should be considered in the differential diagnosis of even very young children presenting with ascites.

Ascites↗

Pathophysiology and management of pediatric ascites.

Ascites accumulation is the product of a complex process involving hepatic, renal, systemic, hemodynamic, and neurohormonal factors. The main pathophysiologic theories of ascites formation include the "underfill," "overflow," and peripheral arterial vasodilation hypotheses. These theories are not necessarily mutually exclusive and are linked at some level by a common pathophysiologic thread: The body senses a decreased effective arterial blood volume, leading to stimulation of the sympathetic nervous system, arginine-vasopressin feedback loops, and the renin-angiotensin-aldosterone system. Cornerstones of ascites management include dietary sodium restriction and diuretics. Spironolactone is generally tried initially, with furosemide added if clinical response is suboptimal. More refractory patients require large-volume paracentesis (LVP) accompanied by volume expansion with albumin. Placement of a transjugular intrahepatic portosystemic shunt is reserved for individuals with compensated liver function who require very frequent sessions of LVP. Peritoneovenous shunts are not used in contemporary ascites management. Liver transplantation remains the definitive therapy for refractory ascites. Although treatment of ascites fails to improve survival, it benefits quality of life and limits the development of such complications as spontaneous bacterial peritonitis.

Age Factors↗

Ascites chylomicron: a poor substrate for hepatic triglyceride lipase.

A patient with nephrotic syndrome and morbus Kimura (eosinophilic granuloma) showed chylous ascites. Ascites chylomicrons were analyzed and used to study the substrate specificity of lipoprotein lipase and hepatic triglyceride lipase. Ascites triglyceride and cholesterol concentrations were 191 and 12 mg/dl, respectively. Both apo CII and apo CIII content in ascites were approximately one-third of those of plasma from normal subjects. Ascites chylomicrons were incubated with either lipoprotein lipase or hepatic triglyceride lipase, which were prepared from postheparin plasma using heparin-Sepharose affinity chromatography. Lipoprotein lipase hydrolyzed ascites chylomicrons, while hepatic triglyceride lipase did not. These results suggest different functions of these two lipases in chylomicron catabolism.

Ascites↗

Ascites increases the resting energy expenditure in liver cirrhosis.

The purpose of this study was to investigate the effect of ascites on the energy metabolism of patients with liver cirrhosis. The resting energy expenditure was determined in 10 patients with liver cirrhosis and ascites of moderate or large volume. The resting energy expenditure measurement was performed using indirect calorimetry and the resting energy expenditure predictive value was calculated with the Harris-Benedict equation, both before and after removal of ascitic fluid by paracentesis. Metabolic stress factors were absent in all cases. After an interval of 11.2 +/- 7.7 days between measurements, a weight loss of 16.6 +/- 10.3 kg was observed with paracentesis. The resting energy expenditure measured by indirect calorimetry showed a statistically significant decrease from 1682 +/- 291 to 1523 +/- 240 kcal/day (P less than 0.005) after removal of ascites. The repeatability of our indirect calorimetry method only allowed for the analysis of the results in 4 of 10 patients in whom ascites removal produced a consistent decrease in resting energy expenditure. There were no statistically significant differences between the measurements obtained by indirect calorimetry and those provided by the Harris-Benedict equation, but the latter had a moderate reliability in predicting the real resting energy expenditure of every patient. Our results suggest that, far from being an inert volume, ascites may be associated, at least in some patients, with an increased resting energy expenditure and therefore accelerate the appearance of protein energy malnutrition with corresponding complications.

Adult↗

Bacterial translocation to mesenteric lymph nodes is increased in cirrhotic rats with ascites.

BACKGROUND/AIMS: Cirrhotic patients are predisposed to develop spontaneous bacteremias and/or peritonitis, mainly caused by enteric bacteria. The aim of this study was to investigate if bacterial translocation, which is the passage of bacteria from the intestinal lumen to regional lymph nodes and/or the systemic circulation, is increased in a rat model of cirrhosis. METHODS: Rats were studied after 12-16 weeks of CCl4 inhalation, when samples of mesenteric lymph nodes, blood, liver, and spleen for standard bacteriologic cultures and a fragment of colon and liver for histology were obtained. Immunostaining of the cecum was performed using a polyclonal anti-Escherichia coli antibody. RESULTS: A significantly greater proportion of rats with cirrhosis and ascites (5 of 9; 56%) had positive mesenteric lymph node cultures compared with cirrhotics without ascites (0 of 9) and normal controls (0 of 12) (P < 0.01). In one cirrhotic rat, E. coli was isolated from both mesenteric lymph nodes and ascites. Rats with cirrhosis and ascites had significantly greater cecal submucosal edema and inflammation than rats with no ascites and controls. Immunoreactivity with E. coli was present in the cecal wall in 3 of 5 animals with E. coli translocation to mesenteric lymph nodes. CONCLUSIONS: In cirrhotic rats, bacterial translocation is increased after the development of ascites and may be a major factor in the development of spontaneous infections in cirrhosis.

Animals↗

Massive ascitic fluid loss and coagulation disturbances after liver transplantation.

BACKGROUND & AIMS: A unique syndrome in which massive ascitic fluid loss developing 1-4 weeks after orthotopic liver transplantation (OLT) was associated with a hypercoagulable state and thrombotic complications is described. After OLT, severe coagulation abnormalities (international normalized ratio, 4.6) developed in a patient with ascitic losses of up to 12 L/day. The patient developed hypovolemia and severe systemic antithrombin III deficiency and venoocclusive disease in the graft. The aim of this study was to determine the prevalence of this syndrome after OLT. METHODS: Coagulation studies were performed in 25 additional patients with large ascitic fluid losses after OLT and in 7 cirrhotic patients not undergoing transplantation. RESULTS: All transplant recipients developed systemic deficiencies of multiple coagulation factors including antithrombin III. Markers of prothrombin activation were significantly elevated in both ascites and serum in all patients, and thrombotic complications subsequently developed in 5 patients. In the 7 cirrhotic patients, markers of prothrombin activation remained normal or minimally elevated and thrombotic complications were not found. CONCLUSIONS: Massive ascitic losses after OLT may lead to a hypercoagulable state from unreplaced losses of plasma coagulation factors into ascites and accumulation of thrombin in the systemic circulation. Hypovolemia and major coagulation abnormalities should be corrected with fresh frozen plasma, which may prevent the development of thrombotic complications.

Adult↗

Parameters affecting ascites tumour formation in mice and monoclonal antibody production.

Hybridoma cells injected intraperitoneally into mice induce formation of ascites tumours and production of ascites fluid containing high levels of monoclonal antibody. Several parameters affecting the growth of the immunoglobulin-producing tumours have been studied in order to define optimal conditions for ascitic fluid formation and monoclonal antibody production. Using hybridomas produced by fusing SP2/0 myeloma cells with immunized mouse spleen cells we have shown: (1) that the optimal number of hybridoma cells required to induce an ascites tumour was between 6 and 32 X 10(5) cells; (2) that each mouse should be treated with a maximum of 0.5 ml of pristane; (3) that the priming period for pristane should be 14 days prior to the injection of cells; (4) that ascites formation and monoclonal antibody production is significantly better in males; and finally (5) that the age of mice used should range between 43 and 78 days. Under these conditions each mouse produces on average 7-10 ml of ascites fluid, containing a high level of antibody, over a maximum period of 6 days. The animals should start producing between the 5th and 9th day and usually survive 11-16 days after being injected with the tumour cells.

Animals↗

Enhancement of hybridoma production by medium supplemented with murine ascitic fluid.

We have greatly improved the yield after cell fusion of antigen-specific monoclonal antibody-secreting murine hybridomas by substitution of Sp2/0 ascites for fetal bovine serum (FBS) in the culture medium. As a medium supplement for established cultures, Sp2/0 ascites at 2.5% in Dulbecco's modified Eagle's medium (DMEM) provided growth characteristics similar to media containing 10% or 20% FBS. All culture parameters associated with hybridoma fusion experiments, however, were advantageously affected in ascites-supplemented cultures. Clonal growth of hybridomas from the single cell stage was enhanced at least two-fold over 20% FBS-supplemented medium. Following fusion, both the number of colonies and hybridoma growth rates were substantially increased for ascites-containing cultures. Most importantly, the number of antigen-specific antibody-secreting hybridomas was increased in Sp2/0 ascites supplemented cultures, five-fold in the eight fusion experiments presented here. This improved performance compared to FBS-supplemented medium is reproducible from lot to lot of ascites.

Animals↗