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Spontaneous bacterial peritonitis in cirrhotics: clinical and ascitic fluid findings.

During a two-year period, 30 patients with spontaneous bacterial peritonitis were documented. All patients had ascites and 70% were alcoholic cirrhosis. Fever and abdominal pain were the most frequent presenting manifestations (96.66% and 76.66% respectively). Triads of fever, abdominal pain and rebound tenderness were found in 40%. A third had hepatic encephalopathy and decreased bowel sound. Ascitic fluid was transudate. Positive ascitic fluid culture and blood culture were obtained in 40% and 59% respectively, and three quarters were due to gram negative enteric bacilli. There was no significant statistic correlation among the result of ascitic fluid gram's stain and ascitic fluid culture, and of ascitic fluid culture and blood culture. The clinical and laboratory findings of patients with positive and negative ascitic fluid culture were similar. Significant increased mortality was found in patients who had hepatic encephalopathy, hypotension, increased bilirubin level and serum creatinine. The over all mortality was 33.33%. We recommend abdominal paracentesis in every cirrhotic patients with ascites who were admitted into hospital.

Adult↗

Observations on the mechanism and location of ascites reabsorption in man.

Animal data indicate that ascites is reabsorbed by a lymphatic mechanism and that these vessels are subdiaphragmatic in location. We evaluated the relative role of lymphatics in ascites reabsorption in man by comparing the ascites clearance and plasma appearance rates of intraperitoneally injected radiolabeled albumin to those of intraperitoneally injected labeled autologous red blood cells, which require, owing to their large size, lymphatic removal, in patients with cirrhosis and ascites. To evaluate the location of reabsorption, we repeated these measurements after replacing ascites in the subdiaphragmatic region with 500-1000 ml of intraperitoneally injected air, reasoning that this maneuver should slow or eliminate ascites reabsorption occurring at this site. We found that the transfer rates of albumin and red cells out of ascites were similar and that creation of pneumoperitoneum did not influence these rates. These data confirm that ascites protein reabsorption occurs via a lymphatic mechanism in man. They suggest, however, that these vessels may not be subdiaphragmatic in location.

Absorption↗

The predictive value of physical examinations for ascites.

To determine the predictive value of physical signs for ascites, we compared the results of physical examination with those of abdominal sonography in 90 men in hospital with liver disease. The positive predictive values of shifting dullness and prominent fluid waves were low (51% and 73%). We divided the patients into two groups: those with prolonged prothrombin times (72% prevalence of ascites by sonogram), and those with normal prothrombin times (15% prevalence). In patients with prolonged prothrombin times, a prominent fluid wave had a very high positive predictive value for ascites (96%). Many patients with prolonged prothrombin times had ascites despite negative physical signs. In contrast, in those with normal prothrombin times, both shifting dullness and prominent fluid waves were usually falsely positive. Patients with normal prothrombin times and no shifting dullness rarely (2%) had ascites. The predictive value of physical signs for ascites depends on the prevalence of ascites in groups of patients that are examined. The prothrombin time is a useful index for identifying inpatients with a high or low prevalence of ascites and the predictive value of physical signs is enhanced by interpreting them in combination with a patient's prothrombin time.

Ascites↗

[Evaluation of the diagnostic role of the carcinoembryonic antigen in ascitic fluid].

The diagnostic role of carcinoembryonic antigen (CEA) in ascitic fluid was evaluated in order to assess whether or not ascitic haemorrhage is related to cancer. A total of 30 patients with ascitic haemorrhage were analysed (17 had cirrhosis, 5 non-metastasised cancers and 8 metastasised cancers). CEA radioimmunoassay was performed in serum and ascitic fluid. The results showed that CEA in the ascitic fluid highlighted a clear distinction between the average values of the 3 groups examined serum assay did not. Results were respectively: cirrhotic patients 6.11, non-metastasised cancers 38 and metastasised cancers 204.12. Ascitic fluid measurement revealed considerable variation, especially between the first and third groups examined (p = .00000004). Although CEA must be regarded as an aspecific laboratory test for malignancy, these results suggest that CEA determination in the ascitic fluid may be useful for screening patients with ascitic haemorrhage.

Aged↗

Separation of ascites myeloma cells, lymphocytes and macrophages by zonal centrifugation on an isokinetic gradient.

In attempting to quantitate immunoglobulin synthesis by ascites myeloma cells, we were surprised to note that malignant appearing cells never exceeded 35.9 = 28.0% of ascitic cells and exceeded 22.4 +/- 23.8% of ascitic cells on only one day between the transplantation of the tumor and the death of the host. The ascites tumor suspensions were separated primarily according to diameter, using a previously described isokinetic density gradient of Ficoll in tissue culture medium. This separation resulted in four modal populations of cells: red blood cells, lymphoid cells, macrophages and myeloma cells. The modal populations of macrophages and lymphoid cells always contained less than 0.2% myeloma cells. The purified cells were tested for tumorigenicity. The animal which received the largest number of cells from the macrophage zone received 296 times the number of cells which had been determined to be tumorigenic for myeloma cells. The animal which received the largest number of cells from the lymphoid zone received 1600 times the tumorigenic dose for myeloma cells. Neither of these animals has become ill 4 months after receiving the purified cells. We conclude that: a) Experimentalists who use ascites tumors are not justified in assuming that even easily detected quantitative differences between benign and malignant tissues would be reflected in analyses performed using unstandardized unexamined ascites tumor suspensions. b) In the case of the MOPC 104 mouse myeloma, cytologic criteria are adequate for distinguishing malignant cells from the inflammatory cells in the ascites suspension with a high degree of correspondence between cytologic appearance and biologic activity. c) Programmed gradient sedimentation in an isokinetic gradient of Ficoll in tissue culture medium is an effective means of separating malignant cells from benign cells in this particular ascites tumor.

Animals↗

The mechanism of ascitic fluid protein concentration increase during diuresis in patients with chronic liver disease.

The mechanism of increase in the protein concentration of ascitic fluid during diuresis was investigated in 27 patients with chronic liver disease. The albumin concentration increased in ascites from .58 +/- .49 gm.% in the initial paracentesis to 1.48 +/- .69 gm.% in the final paracentesis (P less than .001) as the serum albumin concentration increased from 2.40 +/- .44 gm.% 2.94 +/- .56 gm.% (P less than .001). The serum to ascites albumin concentration gradient decreased significantly from 1.82 +/- .39 gm.%-1.46 +/- .45 gm.% (P less than .001). Despite this decrease, the serum to ascites albumin concentration gradient was relatively constant (decrease of .36 gm.% or 20% of initial value) compared to either the absolute or percentage change in ascites total protein concentration (increase of 1.48 gm.% or 107% of initial value). In four patients studied prospectively, the plasma volume did not change (3.53 +/- .80 1.-3.73 +/- .59 1.) during diuresis, despite increase in total intravascular albumin (85.7 +/- 25.6 gm.-99.9 +/- 22.3 gm.; P less than .05) and decrease in total albumin in combined intravascular and peritoneal compartments (156.0 +/- 30.1 gm.-143.4 +/- 35.3 gm.; P less than .05). Since neither concentration without decrease in plasma volume or synthesis of protein without increase in total compartmental protein appear to be the major mechanism of serum protein concentration increase, the increase in serum protein concentration was attributed to redistribution of protein from ascites to the intravascular compartment. The increase in ascitic fluid protein concentration during diuresis can be attributed to an increase in serum protein concentration in the presence of the relatively stable serum to ascites albumin concentration gradient.

Ascitic Fluid↗

Pathogenesis of ascites tumor growth: angiogenesis, vascular remodeling, and stroma formation in the peritoneal lining.

In the accompanying papers, we demonstrated that two murine ascites tumors (MOT and TA3/St) induced peritoneal lining blood vessels to become hyperpermeable to plasma proteins, leading to extravasation of fibrinogen and its clotting to cross-linked fibrin in peritoneal lining tissues (peritoneal wall, mesentery, and diaphragm). In solid tumors, vascular hyperpermeability and fibrin deposition lead to the generation of vascularized connective tissue. In order to determine whether fibrin had similar consequences in ascites tumors, the vasculature and stroma of peritoneal lining tissues were analyzed at successive intervals after i.p. tumor cell injection. In both MOT and TA3/St ascites tumors, the size and number of peritoneal lining microvessels increased significantly by 5-8 days. Subsequently, peritoneal lining vessels increased in cross-sectional area by as much as 15-fold and peritoneal vascular frequency increased by up to 11-fold. Incorporation of [3H]thymidine by mesenteric blood vessels was negligible in control animals but came to involve 20 and 40% of endothelial cells lining mesenteric vessels in MOT and TA3/St ascites tumor-bearing mice, respectively. After an early dramatic increase in cross-sectional area, peritoneal lining microvessels subsequently underwent a novel form of remodeling to smaller average size as the result of transvascular bridging by endothelial cell cytoplasmic processes. Thus, both of the ascites tumors studied here induced angiogenesis and stroma similar to that elicited when these same tumors were grown in solid form. However, stroma developed more slowly in ascites than in solid tumors and was entirely confined to a compartment (peritoneal lining tissues) that was distinct from that (peritoneal cavity) containing the majority of tumor cells and ascites fluid. These findings are consistent with the hypothesis that vascular hyperpermeability, induced in both solid and ascites tumors by tumor cell-secreted vascular permeability factor, is a common early step in tumor angiogenesis, resulting in fibrinogen extravasation, fibrin deposition, and likely other alterations of the extracellular matrix that together stimulate new vessel and fibroblast ingrowth.

Animals↗

[Changes of cytokine levels in ascitic fluid after intraperitoneal administration of OK-432 or CDDP].

In order to evaluate the biological response after intraperitoneal administration of OK-432 and CDDP, we studied the changes of cytokine levels in ascitic fluid. A total of 53 gastric cancer patients were included in this study. OK-432 20KE was administered in 7 patients and CDDP was administered in 4 patients intraperitoneally during operation. The IL-6, IL-8, TNF-alpha and sTNF RI levels in ascitic fluid were measured from 0 to 5 postoperative day. These results were compared with those obtained from the control groups (42 patients). The ascitic level of IL-6 increased immediately after operation, then gradually decreased. The elevations of IL-6 from 0 to 5 postoperative day were remarkably higher in the OK-432 treated group, and those on 0 and 1 postoperative days were remarkably lower in CDDP treated group than in the control group. Similarly, the ascitic level of IL-8 elevated soon after operation and then decreased gradually. In the OK-432 treated group, the ascitic level of IL-8 was significantly higher than in the control group from 0 to 2 postoperative day. Ascitic TNF-alpha was detectable only in the ascites soon after operation in the OK-432 treated group. The ascitic level of sTNF RI peaked on 2 postoperative day in the control and the OK-432 treated group and 1 postoperative day in the CDDP treated group. There were no significant differences between these groups.

Aged↗

The intraabdominal pressure in decompensated cirrhosis: relationship with ascites volume and turn-over.

The values of the intraabdominal pressure (IAP) were determined in 23 subjects with decompensated cirrhosis, both in basal conditions and after diuretic treatment (furosemide 75 mg/day orally for one week). In order to investigate the role of IAP in the regulation of ascites turn-over, ascites volume and free-water peritoneal clearance (FWPC) were estimated in the same patients by means of a methylene-blue dilution method. In wash-out conditions, no linear correlation was found between IAP and the values of ascites volume or FWPC. After diuretic treatment, we observed a significant reduction of ascites volumes (from 9.0 +/- 0.98 to 4.9 +/- 0.6 litres; p < 0.0005), IAP (from 17.5 +/- 1.3 to 11.3 +/- 0.8 cmH2O; p < 0.0005) and FWPC (from 99.8 +/- 6.7 to 76.2 +/- 6.6 ml/min; p < 0.001). In this situation, IAP values showed a significant linear correlation both with ascites volumes and clearances. These results may be due to the different weight of the two components of total IAP (hydrostatic pressure and abdominal tension): in the untreated patients (with larger ascites volumes) a considerable amount of the total IAP originates from the abdominal tension, and the correlation between IAP and ascites volumes or turn-over is biased. In the treated subjects (with lower ascites volumes) the tension component is minimal, and the correlation is resumed.

Adult↗

High serum and ascitic soluble interleukin-2 receptor alpha levels in advanced epithelial ovarian cancer.

This study was undertaken to determine if advanced epithelial ovarian cancer was associated with increased serum and ascitic levels of soluble interleukin-2 receptor alpha (sIL-2R alpha). Serum and ascitic fluid samples from 23 ovarian cancer patients were analyzed for sIL-2R alpha using an enzyme-linked immunosorbent assay and compared with the serum and peritoneal levels in 18 normal females. The samples were analyzed for CA-125 levels using a radioimmunoassay and the total protein was also measured. Normal individuals had low serum levels of sIL-2R alpha (367.5 +/- 44.6 U/mL), with similar levels of sIL-2R alpha in the normal peritoneal fluid (438.6 +/- 48.8 U/mL). In contrast, the serum and ascitic fluid levels in ovarian cancer patients were significantly higher (746.7 +/- 82.9 U/mL, P = .0006; 2,656.7 +/- 373.7 U/mL, P = .00002, respectively). The results for sIL-2R alpha were also significant when the levels were expressed per milligram of total protein. More importantly, in almost every ovarian cancer patient the ascitic sIL-2R alpha level far exceeded the serum level, a pattern also observed for CA-125. There was no correlation between the serum and ascitic sIL-2R alpha levels, or between the serum and ascitic CA-125 levels. Although the serum levels of sIL-2R alpha and CA-125 were elevated in the same patient, overall there was no correlation between the serum sIL-2R alpha and serum CA-125 levels, either when the levels were expressed in absolute units or per milligram of total protein. Similarly, there was no correlation between sIL-2R alpha and CA-125 levels in individual ascitic samples. While CA-125 levels may reflect an independent index of tumor burden, these results suggest that selective accumulation of sIL-2R alpha in the ascites may be one of the factors associated with the known nonresponsiveness of the infiltrating lymphocytes against ovarian carcinoma cells.

Antigens, Tumor-Associated, Carbohydrate↗

[Transjugular intrahepatic portosystemic shunt in the treatment of refractory ascites in 21 patients].

OBJECTIVE: To determine the value of the transjugular intrahepatic portosystemic stent shunt (TIPS) in the treatment of patients with cirrhosis and refractory ascites. DESIGN: Descriptive follow-up study. SETTING: University Hospital Gasthuisberg, Leuven, Belgium. METHODS: In a period of three years, 21 consecutive patients with cirrhosis and refractory ascites were treated with TIPS. Refractory ascites was defined as ascites resistant to maximum diuretic therapy and repeated paracentesis. The mean follow-up was 9 months (range 3-26). RESULTS: Creation of the stent shunt was technically successful in 20 patients and resulted in a decrease of the pressure gradient between the portal vein and the inferior vena cava by approximately 47%. The procedure was immediately lethal in two patients. Complications occurred later on in four patients: thrombosis of the stent in 3 patients and disabling encephalopathy in one. Five other patients died from liver failure, four of them possibly related to the increase of the portosystemic shunting. The stent shunt had no ill effects on kidney function. Thirteen patients were still alive at the end of follow-up. Five patients (24%) had a total and sustained remission of the ascites. Seven patients (33%) still had ascites but needed no paracentesis. One patient did not respond to the treatment. The best results were observed in 14 alcoholics: 9 (64%) responded favourably (43% in non-alcoholics), in 4 of these the ascites had disappeared. CONCLUSIONS: TIPS placement needs substantial experience to avoid technical complications. In case of refractory ascites, only patients for whom later liver transplantation is considered should be submitted to the procedure, because TIPS placement can lead to deterioration of liver function.

Ascites↗

Peritoneovenous shunting for malignant ascites.

AIM: Malignant ascites may produce a cluster of symptoms including abdominal distension, early satiety, respiratory embarrassment, impaired mobility and lethargy. Successful relief of these symptoms is often difficult to attain. We report on the use of peritoneovenous shunting in a group of patients with troublesome malignant ascites with particular reference to the effectiveness and complications of the procedure. METHODS: Twenty one Denver peritoneovenous shunts were placed in 19 patients with malignant ascites. The patients included 16 females and three males and had a median age of 54 years. All had previously been treated with vigorous diuretic therapy and/or repeated paracentesis. Shunt insertion was carried out under general anaesthetic in a manner similar to that described by others. RESULTS: The procedure was well tolerated by most patients. Median hospital stay was 6 days. One patient died 11 days after her surgery from what was thought to be an unrelated cause. Another patient suffered major problems after shunt insertion from exacerbation of pre-existing pleural effusions. All other complications were minor and self limiting. Two shunts failed to function within the first week. Excellent shunt function with resolution of ascite and of associated symptoms was seen in 16 patients. In five late shunt occlusion occurred with resulting reaccummulation of ascites but in four of these shunt function was able to be restored. Median survival in the 18 patients who survived the procedure was 5.5 months and in 14 of these the shunt was functioning at the time of death with good control of ascites. CONCLUSION: Malignant ascites can result in very troublesome symptoms for patients who may otherwise have some time to live. Peritoneovenous shunting is a well tolerated relatively minor surgical procedure which can achieve excellent control of ascites in the majority of such patients.

Adolescent↗

A simple bedside manoeuvre to detect ascites.

BACKGROUND: Shifting dullness and fluid wave are two techniques commonly used to detect ascites. However, these may fail to detect moderate or minimal ascites. Ultrasonography is a good non-invasive method to detect ascites but may not be available in distant rural areas of India. We assessed the utility of the puddle sign and auscultatory percussion for detecting ascites. METHODS: Sixty-six patients with suspected ascites were included in the study. Those with a previous history of ascites, or therapeutic paracentesis and in whom ascites was detected by shifting dullness or fluid wave were excluded. The puddle sign and auscultatory percussion were elicited in all the patients. Ultrasonography was used as the gold standard. To eliminate any observer bias the investigators were blinded to each others' findings. RESULTS: Auscultatory percussion had a greater sensitivity (65.7% v. 45%, p < 0.05) but a lower specificity than the puddle sign (48.4% v. 67.7%, p < 0.05). There were no significant differences between positive and negative predictive values and the positive and negative likelihood ratios. CONCLUSION: Auscultatory percussion is a better method than puddle sign for detecting ascites as it has a greater sensitivity.

Adult↗

Stimulation of albumin synthesis in rat hepatocytes by ascites from patients with cirrhosis.

Hepatocyte growth factor (HGF), identified in ultrafiltered ascites and plasma from patients with cirrhosis, enhances the DNA synthesis in adult rat hepatocytes cultured at low cell density. This study was carried out to investigate the effect of ascites and plasma from patients with cirrhosis on liver-specific functions such as albumin synthesis in adult rat hepatocytes cultured at confluent-cell density. Ultrafiltered ascites from patients with cirrhosis and its ascitic protein, partially purified by fractionation with ammonium sulfate and gel filtration on Sephadex G-200, stimulated albumin synthesis in a dose-dependent manner in the presence of 10(-8), M dexamethasone. This effect was greater than that of 10(-7) M insulin and similar to that of 10(-7) M dexamethasone, but was additive with that of insulin plus dexamethasone. The molecular weight of the ascitic factor was estimated as 100,000 to 150,000, corresponding to that of HGF purified from cirrhotic ascites. Moreover, the partially purified ascitic factor markedly stimulated DNA and protein synthesis in hepatocytes. These findings suggest that the ascitic factor may act as HGF by stimulating hepatocyte DNA and albumin synthesis in a cell density-dependent manner.

Aged↗

[Experimental methods in hepatology. Guidelines of the German Work Group for Study of the Liver. Therapy of ascites in liver diseases. German Work Group for Study of the Liver].

Patients with "uncomplicated" ascites (no encephalopathy, electrolyte derangements or markedly impaired renal function) respond well to the conventional sequential therapy comprising dietary sodium restriction, aldosterone antagonists and loop diuretics. A close monitoring of the patients is important to avoid side effects. For massive ascites, ascites refractory to diuretic treatment or recidivant ascites daily therapeutic paracentesis is recommended. Four to six liters of ascites should be drained daily followed by infusion of plasma expanders (preferentially albumin, eventually hemacell or dextran-70) until the patient is almost free of ascites. The diuretic treatment should be instituted. The transjugular intrahepatic portosystemic shunt (TIPS) represents a promising novel therapeutic modality the therapeutic impact of which has to be more clearly defined in prospective studies. Several experimental approaches have been proposed for the therapy of the hepatorenal syndrome (Dopamine, Ornipressin, TIPS). Liver transplantation is the only causal treatment of refractory ascites or hepatorenal syndrome and should be discussed when a patient presents with massive ascites.

Ascites↗

[Current treatment of ascites and spontaneous bacterial peritonitis in Spain: analysis of a survey of gastroenterologists and hepatologists].

During the XXII Congress of the Spanish Association for the Study of the Liver a questionnaire was distributed with the aim of describing the current therapeutic attitude of those attending the meeting, concerning two of the most frequent complications of cirrhosis: ascites and spontaneous bacterial peritonitis (SBP). One hundred twelve of the 135 physicians who answered the questionnaire (83%) use to treat tense ascites by therapeutic paracentesis, while 86 physicians (63.7%) managed moderate ascites with diuretics, with spironolactone being the drug most commonly used (n = 117; 87.3%). The most used diuretic schedule for the treatment of ascites was the isolated administration of spironolactone. Frusemide was associated with spironolactone only when moderate or high doses of the latter were found to be insufficient for increasing urinary sodium excretion and eliminating ascites. Following therapeutic paracentesis however, 79 of those surveyed (58.3%) administered a combination of both diuretics on initiation to avoid reaccumulation of ascitic fluid. Sixty-eight of the physicians (50.3%) used transhepatic intrajugular portosystemic shunt in the treatment of refractory ascites. Cefotaxime was the antibiotic most widely used in the treatment of SBP (n = 119; 88%). Most of the physicians surveyed performed prophylaxis of this infection (generally by the oral administration of norfloxacin) in patients with a previous history of SBP (n = 125; 92.6%) or an episode of gastrointestinal hemorrhage (n = 108; 80%) but not in those patients with no previous history of SBP and with low protein concentrations in the ascitic fluid (n = 40; 29.6%). On the appearance of SBP in patients undergoing prophylactic treatment, cefotaxime remained the antibiotic of choice (n = 104; 79%).

Ascites↗

[Ascites due to hypothyroidism].

A 77-year-old man presented with ascites which was due to hypothyroidism. After the ascites had been brought into remission by salt restriction, diuretics and paracentesis, monotherapy with levothyroxine prevented recurrence. Ascites reappeared as soon as levothyroxine was withdrawn due to the patient's non-compliance. Distinctive aspects of this type of ascites are the high concentration of total protein in the ascites and the high serum-to-ascites albumin gradient (SAAG). The pathogenesis of ascites in hypothyroidism is unknown. Possible hypotheses include increased capillary permeability, obstruction to lymphatic flow caused by hyaluronic acid-albumin complexes, and diminished water diuresis due to excess antidiuretic hormone. A patient with unexplained ascites should be tested for hypothyroidism, especially when the SAAG is high (> 11 g/l).

Aged↗

[Pharmaco-dynamic influence under ascites or laparotomy on intraperitoneal sequential MTX/5-FU therapy].

We studied pharmaco-dynamic changes of intraperitoneal sequential MTX (30 mg)/5-FU (750 mg) therapy in gastric cancer patients with malignant ascites and those who had undergone a gastrectomy. The serum and ascites levels of MTX in patients with malignant ascites decreased much slower than in patients without ascites. In patients with ascites, the serum MTX concentration peaked 8 hours later and then gradually decreased. The ascites MTX level decreased as low as 1/10 2 days after the intraperitoneal administration. The serum and ascites 5-FU levels revealed a minor prolongation of 5-FU concentration in patients with ascites. Gastrectomy did not affect the pharmaco-dynamics of MTX in post-operative patients with sequential intraperitoneal administration of MTX/5-FU on 1, 8 and 15 POD.

Antineoplastic Combined Chemotherapy Protocols↗