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PubMedDate not supplied

Patients with deficient ascitic fluid opsonic activity are predisposed to spontaneous bacterial peritonitis.

To assess the risk of development of spontaneous bacterial peritonitis in relation to ascitic fluid opsonic activity, routine admission abdominal paracentesis was performed on 119 patients during 141 hospitalizations. Paracentesis was repeated if evidence of peritonitis developed during the hospitalization. The ascitic fluid opsonic activity (0.2 +/- 0.5 log kill) of 24 spontaneously infected specimens was significantly (p less than 0.001) lower than that of the group with sterile portal hypertension-related ascites (0.8 +/- 1.1 log kill), and significantly lower than the group with ascites of miscellaneous type (2.4 +/- 1.0 log kill, p less than 0.001). The C3 and C4 concentrations of the spontaneous peritonitis specimens were also significantly lower than in the specimens from the other groups. Of the 55 patients whose initial sterile ascitic fluid opsonic activity was less than 0.2 log kill, 8 (14.5%) developed spontaneous bacterial peritonitis during the hospitalization; whereas none of the 70 patients with sterile ascitic fluid opsonic activity greater than or equal to 0.2 log kill developed spontaneous peritonitis. This difference in the risk of development of peritonitis was significant (p less than 0.01). Patients with deficient ascitic fluid opsonic activity are predisposed to spontaneous bacterial peritonitis.

Ascitic Fluid↗
PubMed1994

Effects of large-volume paracentesis on pulmonary function in patients with tense cirrhotic ascites.

Large-volume paracentesis is an accepted therapeutic modality for the treatment of tense ascites in patients with cirrhosis. Whereas the effects of large-volume paracentesis on the cardiovascular system have been studied in great detail, the effects of tense ascites and large-volume paracentesis on the respiratory system have undergone only limited evaluation. Most patients report symptomatic improvement in breathing after large-volume paracentesis. The aim of our study was to prospectively evaluate the effects of large-volume paracentesis on the pulmonary function of patients with tense ascites. Nine patients with alcoholic cirrhosis and tense ascites underwent large-volume paracentesis (mean, 3,500 ml of ascites removed) followed by intravenous albumin infusion (10 gm/L ascites removed). Pulmonary function tests were performed just before and 2 hr after large-volume paracentesis. The functional residual capacity increased from 2.46 +/- 0.92 to 2.99 +/- 0.97 L (p = 0.01) and total lung capacity from 5.08 +/- 1.18 to 5.72 +/- 1.32 L (p = 0.03). The forced vital capacity, expiratory reserve volume and residual volume also increased but were not statistically significant (p = 0.07 for all). We noted no significant improvement in forced expiratory volume in 1 sec, forced expiratory effort 25% to 75%, vital capacity or diffusion capacity. There was marked symptomatic improvement in all patients. We conclude that large-volume paracentesis improves measured lung volumes within hours in patients with tense ascites.

Ascites↗
PubMed1995

Long-term effect of nadolol or nadolol plus isosorbide-5-mononitrate on renal function and ascites formation in patients with cirrhosis. GTIP Gruppo Triveneto per l'Ipertensione Portale.

The association beta-blockers plus nitrates has been reported to impair renal function and renal sodium handling, leading to increased risk of development of ascites, or worsening of a preexisting ascites, or increase in the requirements of diuretic agents. In 81 patients with cirrhosis and esophageal varices, participating in a multicenter controlled clinical trial of prophylaxis of variceal bleeding comparing nadolol (NAD) plus isosorbide-5-mononitrate (I5M) with NAD alone, renal function, presence of ascites, and diuretic requirements were assessed at inclusion and after 6 months of follow-up. No significant variation in s-urea or s-creatinine was observed in either group, Three patients in the nadolol group and two in the NAD plus I5M developed ascites at 6 months (P = .70), and a need to increase diuretic regimen was observed in four and three patients, respectively (P = .76). Decrease in heart rate and in mean arterial pressure was similar in the two groups. There was a significant correlation between increases in s-creatinine and decrease in mean arterial pressure in the whole series (P = .015). Only in patients treated with the association was there a significant larger proportion of patients ascitic who became anascitic, than of patients anascitic who became ascitic (P = .03). In patients treated with the association, there was a significantly larger decrease in hepatic venous pressure gradient (P = .05). It is concluded that patients treated with the association NAD plus I5M are not at increased risk of developing renal dysfunction or worsening of ascites compared with patients treated with NAD alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2006

The effect of single oral low-dose losartan on posture-related sodium handling in post-TIPS ascites-free cirrhosis.

Post-TIPS ascites-free patients with cirrhosis and previous refractory ascites demonstrate subtle sodium retention when challenged with a high sodium load. This is also observed in pre-ascitic patients with cirrhosis. This phenomenon is dependent on an intrarenal angiotensin II (ANG II) mechanism related to the assumption of erect posture. We investigated whether similar mechanisms were involved in post-TIPS ascites-free patients, by studying 10 patients with functioning TIPS and no ascites. We measured the effect of changing from supine to erect posture on sodium excretion at baseline and after single oral low dose losartan (7.5 mg) which has been shown to blunt proximal and distal tubular sodium reabsorption in pre-ascites. At baseline, the assumption of erect posture produced a reduction in sodium excretion (from 0.30+/-0.06 to 0.13+/-0.02 mmol/min, P=.05), which was mainly due to an increase in proximal tubular reabsorption of sodium (PTRNa) (69.7+/-3.1% to 81.1+/-1.8%, P=.003). The administration of losartan resulted in a blunting of PTRNa (supine 69.7+/-3.1% to 63.9+/-3.9%, P=.01 and erect 81.1+/-1.8% to 73.8+/-2.4%, P=.01), accompanied by an increased distal tubular reabsorption of sodium in both postures, with no overall improvement in sodium excretion on standing. In conclusion, post-TIPS ascites-free patients with cirrhosis exhibit erect posture-induced sodium retention. We speculate that (1) this effect is partly mediated by the effect of ANG II on PTRNa and (2) that the inability of low dose losartan to block the erect posture-induced sodium retention may be related to the erect posture-induced rise in aldosterone which is unmodified by losartan.

Administration, Oral↗
PubMed1998

Increased cerebrovascular resistance in cirrhotic patients with ascites.

Studies assessing regional hemodynamics in patients with cirrhosis and ascites have shown vasodilation in the splanchnic circulation and vasoconstriction in the renal circulation and in the brachial and femoral artery vascular territories. The aim of this study was to assess the cerebral vascular resistance in cirrhotic patients with ascites. The resistive index in the middle cerebral artery (an index of the cerebral vascular resistance) and in a renal interlobar artery were measured by Doppler ultrasonography in 7 healthy subjects: 13 patients with compensated cirrhosis and 24 patients with ascites (13 with renal failure). The arterial blood pressure and the activity of the renin-angiotensin and sympathetic nervous systems, as estimated by plasma renin activity and plasma norepinephrine concentration, respectively, were also measured. The resistive index in the middle cerebral artery was significantly increased in patients with ascites (0.68 +/- 0.05, mean +/- SD) as compared with patients without ascites (0.60 +/- 0.01, P < .05) and with healthy patients (0.52 +/- 0.01, P < .01). Renal resistive index was also increased in patients with ascites (0.77 +/- 0.01) compared with the other two groups (0.68 +/- 0.02 and 0.62 +/- 0.00, respectively; P < .001). The resistive index in the middle cerebral artery showed a direct correlation with renal resistive index (r = .73, P < .01), plasma renin activity (r = .61, P < .01), and norepinephrine (r = .53, P < .01). The resistive index in the middle cerebral artery showed an inverse correlation with mean arterial pressure (r = -.45, P < .01). These results indicate that in patients with cirrhosis and ascites there is a cerebral vasoconstriction which is probably related with the arterial hypotension and the overactivity of vasoconstrictor systems.

Adult↗
PubMed2002

Intraperitoneal bispecific antibody (HEA125xOKT3) therapy inhibits malignant ascites production in advanced ovarian carcinoma.

Bispecific antibody HEA125 x OKT3 was shown to redirect T lymphocytes toward carcinoma cells and to induce tumor cell lysis in vitro. Preclinical studies have demonstrated that tumor-associated lymphocytes (TAL) derived from malignant ascites can be used as effector cells with a high efficacy and without prior stimulation. These data provided the rationale for a clinical trial to investigate whether bsAb HEA125 x OKT3 is also able to induce tumor cell lysis in vivo and can be used for local treatment of malignant ascites arising from ovarian carcinoma. Ten ovarian carcinoma patients presenting with malignant ascites resistant to chemotherapy were enrolled in the study. They received weekly intraperitoneal injections of 1 mg bsAb diluted in 500 ml NaCl solution to allow homogeneous antibody distribution within the peritoneal cavity. All patients responded clinically well to the therapy. Eight patients experienced a complete and 2 patients a partial reduction of ascites production. A decrease or stabilization of tumor marker CA125 was detected in the sera of 8 patients. Only WHO Grade I and II toxicity was observed including mild fever, chills and allergic eczema. Thus, intraperitoneal application of bsAb HEA125 x OKT3 appears to be an easy and cost effective palliative treatment for ovarian carcinoma with recurrent ascites that leads to a substantially increased quality of life for the patients. During therapy TNF-alpha concentrations raised markedly in the ascites fluid whereas VEGF and sFLT-1 ascites levels declined. This indicates that not only T cell-mediated tumor cell lysis but also changes in vascular permeability due to downregulation of VEGF and its receptors might be responsible for the beneficial therapeutic effect.

Antibodies, Bispecific↗
PubMed1994

The causes and natural history of fetal ascites.

The purpose of this study was to examine the natural history and differential diagnosis of ultrasound-detected, isolated fetal ascites. Retrospective review of our patient data base, from 1989 to 1993, revealed 18 patients with fetal ascites diagnosed sonographically. Fetuses presenting with generalized hydrops were excluded. One of the 18 fetuses with ascites had a chromosomal abnormality (trisomy 21), four fetuses had intrauterine infections, seven had gastrointestinal processes, two had genitourinary tract abnormalities, and four were labelled as 'idiopathic' (all four resulting in normal neonates). Seventeen of 18 fetuses survived; there was one fetal demise secondary to active syphilis. One fetus with parvovirus infection required intrauterine transfusion and did well. Two infants are developmentally retarded, including one with trisomy 21 and one with microcephaly secondary to cytomegalovirus infection. Fourteen of 18 fetuses had documented in-utero resolution of the ascites. Eleven of the 18 were associated with polyhydramnios sometime during fetal life. None of the fetuses developed hydrops. In conclusion, fetal ascites can result from many different aetiologies, including gastrointestinal and genitourinary anomalies. Chromosomal abnormalities and viral aetiologies must also be considered. Fetuses who have isolated ascites can have a good outcome with resolution of the ascites antenatally.

Ascites↗
PubMed1980

Pharmacokinetics of 1-alkylcarbamoyl-5-fluorouracils in plasma and ascites fluid after oral administration in mice.

Pharmacokinetics of 1-alkylcarbamoyl-5-fluorouracils was examined in mice bearing sarcoma 180. The alkylcarbamoyl derivatives were absorbed rapidly as intact form through the gastrointestinal tract and distributed into ascites fluid. Concentration-x-time (C-x-t) values of 5-fluorouracil formed in plasma and ascites fluid decreased in order by extension of the carbon chain of the alkyl moiety. C-x-t value of 5-fluorouracil formed in ascites fluid after hexylcarbamoyl derivative was higher than that in plasma. Antitumor activity of the compounds was correlated with both maximum concentration (Cmax) and C-x-t values of 5-fluorouracil formed and Cmax of total (intact form plus 5-fluorouracil formed) in ascites fluid (P < 0.01), and with C-x-t values in ascites fluid and Cmax and C-x-t values of 5-fluorouracil formed in plasma (P < 0.05). Alkylcarbamoyl structure was valuable for rapid absorption through the gastrointestinal tract and blood-ascites barrier and for maintenance of 5-fluorouracil level in plasma and ascites fluid.

Administration, Oral↗
PubMedDate not supplied

Role of surgical therapy in management of intractable ascites.

Almost 10% of patients with cirrhosis and ascites develop intractable ascites. When large-volume paracentesis fails to relieve ascites, patients may be submitted to one of the three following surgical options: portosystemic shunting, peritoneovenous shunting, or liver transplantation. Portosystemic shunting is efficient in clearing ascites, but it is associated with a high rate of encephalopathy and liver failure. The indications for portosystemic shunting are therefore limited for treatment of intractable ascites and should be performed only in patients with good liver function in whom all other treatments failed. Peritoneovenous shunting has been associated with a high rate of early complications and valve obstruction. Improvements in perioperative care and in the material used have greatly reduced the operative risks and increased the patency rate. Mortality remains high in patients with severe liver failure or with a history of spontaneous bacterial peritonitis or variceal bleeding. Peritoneovenous shunting should not be done when these risk factors are present. In the absence of such risk factors, peritoneovenous shunting is a good procedure and may provide definitive relief of ascites and long-term survival in more than 50% of the operated patients. In patients with poor risk factors liver transplantation may be preferable, and the onset of intractable ascites in a patient with a severely compromised liver should trigger the indication of liver replacement.

Ascites↗
PubMed1989

Effects of lymphokine-activated killer cells and interleukin-2 on the ascites formation and the survival time of nude mice bearing human ovarian cancer cells.

The effect of intraperitoneal instillations of interleukin-2 (IL-2) and/or lymphokine-activated killer (LAK) cells on the ascites formation and the survival time was examined using nude mice as a model, with malignant ascites produced by intraperitoneal inoculation of human ovarian cancer cells derived from ascites of a patient with serous cystadenocarcinoma of the ovary. Twenty-eight days after tumor inoculation, all nude mice in the untreated group and in the group treated with spleen cells alone formed ascites. Two of ten nude mice treated with IL-2 alone after tumor inoculation survived without forming ascites during the experimental period. On the other hand, all nude mice treated with LAK cells alone had formed ascites 14 days after tumor inoculation. When LAK cells and IL-2 were combined, five of ten mice survived without forming ascites during the experimental period. The survival time of the group treated with IL-2 alone was significantly prolonged compared to the groups that received medium alone, spleen cells alone and LAK cells alone. When administration of LAK cells was followed by IL-2, the survival time was further prolonged.

Animals↗
PubMed1991

Generation of lymphokine-activated killer cells in human ovarian carcinoma ascitic fluid: identification of transforming growth factor-beta as a suppressive factor.

The effect of cell-free ascitic fluid from patients with epithelial ovarian carcinoma on the generation of lymphokine-activated killer cells (LAK) was compared to the activity generated in control medium containing 10% fetal bovine serum, using Daudi target cells. Samples of ascitic fluid from nine different patients tested inhibited LAK generation. Suppressive activity was evident as early as 24 h of incubation in the presence of ascitic fluid and increasing suppression developed with prolonged exposure. Suppression was concentration-dependent, present at 10%-20% and increasing with concentrations up to 80%. The suppressive effect of ascitic fluid was only partially reversed on increasing the concentration of interleukin-2 (IL-2) from 10 units to 1000 units/ml. Activated LAK appeared to maintain the majority of their activity on further culture in ascitic fluid in the presence of IL-2 but further enhancement of lytic activity was prevented. Fractionation of a suppressive sample by HPLC, using 0.1 M KCl/acetic acid buffer pH 2.6, revealed that the dominant peak of suppressive activity eluted at 25 kDa; with pH 7.0 TRIS-buffered saline, most of the activity was lost on the column. Antibody neutralization studies of the 25-kDa suppressive peak as well as on whole ascitic fluid have revealed that transforming growth factor beta (TGF beta) is the major suppressive factor present in ascitic fluid. Factors that suppress LAK generation in vitro were present in all samples tested. The effect on the lytic activity of activated LAK cells was minimal. This suggests that, in the clinical setting, the greatest impact would be achieved by activating LAK cells ex vivo and subsequently transferring them to the peritoneal cavity in the presence of IL-2 rather than by attempting to generate them in situ by injecting IL-2 into the peritoneal cavity. However, reversal of TGF beta-mediated suppression in situ may be necessary to allow local proliferation of LAK cells to achieve an effective killer-to-target ratio.

Ascitic Fluid↗
PubMed1988

A DIC-like picture on plasma and ascitic fluid of cirrhotic patients.

Ascitic fluid reinfusion in severe cirrhosis has frequently been associated with intravascular coagulation (DIC). A low-grade DIC has been postulated to be present in liver cirrhosis. PT, APTT, fibrinogen, plasminogen, antiplasmin, fibrin degradation producers (FDP), euglobulin lysis time, tissue plasminogen activator, and fibrinopeptide A were investigated both in the plasma and ascitic fluid of cirrhotic patients before and after the concentration-reinfusion technique. Our results indicate that increased thrombin formation associated with hyperfibrinolysis is present in the plasma of cirrhotic patients. In ascitic fluid very high levels of thrombin and fibrinolysis activation were found. We conclude that (1) a DIC-like picture exists in ascites and (2) after ascites reinfusion procedures, ascitic fluid is the principal factor in the pathogenesis of DIC. During ascitic fluid reinfusion heparin treatment could be used successfully.

Aged↗
PubMed1995

Prevalence and prognostic significance of bacterascites in cirrhosis with ascites.

The prevalence and prognostic significance of bacterascites (BA) were prospectively studied in 443 predominantly HBsAg-positive cirrhotic patients with ascites. Spontaneous bacterial peritonitis (SBP), culture-negative neutrocytic ascites (CNNA), and BA were identified in 12.4%, 8.4%, and 10.8%, respectively. Of these, 67%, 70%, and 71%, respectively, had peritonitis-related signs or symptoms. Among patients with SBP or CNNA, the clinical and laboratory data showed no significant difference between the symptomatic and asymptomatic groups. In contrast, among the patients with BA, the symptomatic group had significantly higher levels of serum total bilirubin and prolonged prothrombin time and significantly lower levels of ascitic fluid total protein than the asymptomatic group. Furthermore, the clinical and laboratory data were relatively similar between patients with asymptomatic BA and those with sterile ascites. In contrast, patients with SBP, CNNA, or symptomatic BA exhibited significantly more severe degrees of liver disease and significantly lower levels of ascitic fluid total protein than those with sterile ascites. There was no statistically significant difference between SBP and bacterascites regarding flora. All patients with SBP, CNNA, or symptomatic BA received antibiotic treatment immediately after paracentesis, as did six of the 14 patients with asymptomatic BA for concurrent respiratory or urinary tract infection, while the remaining eight patients with asymptomatic BA were followed clinically without treatment. Repeated paracentesis in the latter revealed no evidence of SBP or CNNA. The in-hospital mortality for sterile ascites was 22.8%, significantly lower than the 54.5% for SBP, 43.2% for CNNA, and 50% for symptomatic BA, but similar to the 21.4% for asymptomatic BA.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascites↗
PubMed1996

Case report: a rare case of chylous ascites from Mycobacterium avium intracellulare in a patient with AIDS: review of the literature.

Chylous ascites is a rare complication of acquired immunodeficiency syndrome (AIDS). Although it is most commonly associated with lymphoma, it has been reported in patients with Kaposi's sarcoma. There has been only one case reported of chyloperitoneum occurring in a pediatric patient as a result of Mycobacterium avium intracellulare (MAI). We report the first case of an adult patient with chylous ascites resulting as a complication of MAI. Chylous ascites (chyloperitoneum) is a rare complication of acquired immunodeficiency syndrome (AIDS). Only two cases of chylous ascites associated with AIDS have been reported in the literature (1, 2). In one case, chylous ascites was attributed to extensive abnormal Kaposi's sarcoma (1). In the second case, a 2-year-old child with Mycobacterium avium intracellulare (MAI) developed chylous ascites. (2) We report the first adult case of AIDS which has been complicated by a MAI infection causing mesenteric lymphadenopathy and chylous ascites.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Endotoxin levels in cirrhotic rats with sterile and infected ascites.

Endotoxin levels were measured in sterile and bacterially infected ascites in a rat model of phenobarbital and carbon tetrachloride induced cirrhosis was used. An improved chromogenic substrate assay was used to measure endotoxin. All rat ascites specimens were positive for endotoxin. In culture-negative ascites (n = 8), it ranged from 0.05 EU/ml to 0.14 EU/ml (0.08 +/- 0.04 EU/ml, mean +/- SD) (Escherichia coli 0111:B4 endotoxin was used as a reference). In culture-positive ascites (premortem n = 3, postmortem n = 1), it ranged from 0.78 EU/ml to 1.8 EU/ml (1.29 +/- 0.59 EU/ml, mean +/- SD). All rats with premortem culture-positive ascites died within two days. This model is useful to study ascites endotoxin levels. In this study, increasing levels of ascites endotoxin correlated with spontaneous bacterial peritonitis and death.

Animals↗
PubMed1990

The role of ascites and phospholipase A2 on peritoneal permeability changes in acute experimental pancreatitis.

Peritoneal permeability to fluorescein-isothiocyanate-conjugated (FITC) dextran, mol wt 10,000 was studied in acute experimental pancreatitis (AEP) in rats. The aim of the study was to elucidate the role of the pancreatitis ascites and its phospholipase A2 activity on the observed peritoneal permeability increase during AEP. Phospholipase A2 activity of ascites was 40 U/microL 1 h after the induction of AEP and decreased during the next 3 h gradually to a plateau of about 20 U/microL, where it remained to the end of the experiment at 24 h. A similar pattern was seen for protein, amylase, and lipase although the initial peak was most pronounced for lipase. Pancreatitis ascites did not--irrespective of its age (1 or 20 h) or incubation time (3-20 h)--affect the peritoneal transport of FITC dextran 10,000 in healthy rats. Similarly, intravenously-administered ascites and intraperitoneal instillation of pancreatic phospholipase A2 dissolved in saline were without effects. On the other hand, in another group of healthy animals, phospholipase dissolved in fresh pancreatitis ascites caused a statistically significant increase of peritoneal transport, as defined. In rats with pancreatitis, the addition of phospholipase A2 to the peritoneal fluid increased peritoneal transport of FITC dextran 10,000 as well as phospholipase A2 itself. We conclude that phospholipase A2 when instilled into the peritoneal cavity in the presence of pancreatitis ascites, has the ability to increase peritoneal permeability to FITC dextran 10,000 in healthy, as well as in pancreatitis rats. However, the phospholipase A2 activity of rat pancreatitis ascites is not sufficient for this mechanism to work. This, however, does not exclude its existence in other species, including humans.

Acute Disease↗
PubMed1988

Insulin and C-peptide in ascitic fluid and plasma and their relative responses to glucagon in patients with cirrhosis.

Insulin (IRI) and C-peptide dynamics were studied after iv glucagon in 5 nondiabetic patients with ascites due to cirrhosis of the liver. Plasma and ascitic fluid samples for glucose, IRI and C-peptide determinations were obtained before and 6, 10, 15, 20 and 30 min after glucagon injection. Ascitic fluid volumes, estimated by dilution of ip injected PAH, were 6.2 to 20.5 L. The mean fasting plasma glucose [88 +/- 6.7 mg/dl (SE)] and C-peptide (1.40 +/- 0.42 ng/ml) levels were normal; mean plasma insulin was increased (17.4 +/- 3.0 microU/ml). After glucagon injection, there was a subnormal rise in plasma glucose (PG) compared to 5 mild diabetic patients without liver disease (8.4 +/- 3.5 vs 76 +/- 7.4 mg/dl). The plasma C-peptide rise was less than that of plasma IRI (54% vs 192%). The mean basal ascitic fluid concentration of glucose was 86 +/- 9.4 mg/dl, IRI 13.2 +/- 2.9 microU/ml and C-peptide 3.09 +/- 0.49 ng/ml. Total calculated basal ascitic fluid contents of glucose was 5.2-23.3 g, IRI 47, 120-290,000 microU and C-peptide 15,750-66,420 ng. These were 3-10 times the quantity of these substances circulating in the plasma volume. After glucagon injection, there was no significant increase in ascitic fluid glucose or IRI, but there was a 43% increase in C-peptide concentration at 10 min. In ascitic fluid, the molar concentration of IRI was lower and C-peptide higher than plasma, resulting in a C-peptide: IRI molar ratio of 11.31, markedly higher than the published normal plasma ratio of 4.63.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1996

Peripheral natural killer cell activity and intraperitoneal soluble p55 tumor necrosis factor receptor in patients with malignant ascites: two possible indicators for response to intraperitoneal combined tumor necrosis factor alpha and interferon gamma treatment.

Tumor necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma) are important immunomodulators. They are capable of acting in a synergistic manner on tumor cells in vitro and in vivo. In a clinical phase I study 13 patients with malignant ascites due to abdominal spread of different primary tumors received intraperitoneally (i.p.) TNFalpha and IFNgamma once weekly over 3-8 weeks in order to evaluate the effect of locoregionally administered TNFalpha/IFNgamma on ascites formation. Therefore some peripheral and local immunological functional parameters of peripheral blood and malignant ascites were investigated. Mononuclear lymphocytes and natural killer (NK) cell activity of peripheral blood and ascites, TNF-inhibitory activity, soluble p55 and p75 TNF receptors, and prostaglandin E2 values in ascites were measured immediately before and 24 h after each TNFalpha/IFNgamma infusion. Peripheral mononuclear lymphocytes and NK activity decreased significantly 24 h after i.p. TNFalpha/IFNgamma application. However, over the entire treatment schedule, peripheral NK activity in all responders showed a continuous increase, when compared to pre TNFalpha/IFNgamma treatment levels. In contrast, NK activity in non-responders constantly decreased. In contrast to non-responders, TNF-inhibitory activity and soluble p55 TNF receptor levels, determined in ascites, decreased in responders. Taken together, our findings suggest, that successful locoregional i.p. TNFalpha/IFNgamma therapy induces systemic immunological reactions possibly after saturation of soluble p55 TNF receptors in ascites, which leads to an increase of peripheral NK activity.

Adult↗