Immunoreactive human chorionic gonadotropin and its free ß-subunit in serum and ascites of patients with malignant tumors

Human chorionic gonadotropin (hCG) is a clinically relevant marker of trophoblastic and nontrophoblastic malignancies. In the present studies, in addition to determining serum hCG, we investigated the presence and properties of hCG immunoreactivity in ascites of patients with nontrophoblastic malignant tumors and, for comparison, in ascites caused by cirrhotic liver disease. Total hCG immunoreactivity [hCG (+hCG-ß)] was found to be elevated above the reference value (>5 IU/liter) in the serum of 2 of 20 patients with cirrhosis and 11 of 20 patients with malignant tumors. For comparison, in ascites, hCG (+hCG-ß) concentrations were frequently higher than in the corresponding serum samples and exceeded 10 IU/liter in 0 of 20 cirrhotic samples and in 16 of 20 malignant samples. In order to elucidate the nature of the hCG immunoreactive material, all samples were then assessed by immunoradiometric assays specific for the intact hCG molecule (holo-hCG) and the free hCG-ß subunit, respectively. In the holo-hCG assay, elevated values were detected in 0 of 20 (0 of 20) cirrhotic ascites (serum) samples and 0 of 20 (1 of 20) malignant ascites (serum) samples. In the free hCG-ß assay, on the other hand, no positive results were obtained in the ascites or serum of 20 patients with liver cirrhosis; however, 8 of 20 serum samples and 16 of 20 ascites samples derived from tumor patients were positive. In accord with the immunological data, gel chromatographical studies of malignant ascites revealed the abundance of free hCG-ß subunit rather than that of holo-hCG. In contrast to malignancy-related ascites, in ascites of patients receiving hCG injections for treatment of infertility, holo-hCG was more abundant than free hCG-ß immunoreactivity. Incubation experiments of purified holo-hCG in ascites for 24 h at -20, 20, or 37°C showed no substantial dissociation of the hCG molecule and release of free hCG-ß immunoreactivity, thus arguing against production of free hCG-ß by degradation of holo-hCG and in favor of its tumor-related secretion. In conclusion, hCG-ß immunoreactivity is frequently elevated in malignancy-related ascites and appears to be related to the presence of free ß subunit of hCG rather than that of the intact hCG molecule. Interestingly, hCG-ß determination in ascites proved to be clearly superior to serum measurement in discriminating between tumor and cirrhosis. Thus, hCG-ß might be a useful marker of malignancy-related ascites and should be prospectively assessed for possible clinical use in comparison with other well-established parameters, such as cytology and protein determination. For this purpose, according to our results, only assays that exhibit a high sensitivity for free hCG-ß subunit appear to be suitable

Pathophysiology of elevated ascites fluid cholesterol in malignant ascites

The existence of marked elevations of ascitic fluid cholesterol has been observed in patients with peritoneal carcinomatosis compared to patients with cirrhosis and has been found useful in differential diagnosis. This finding could be caused by an enhanced movement of plasma lipoproteins into the peritoneal cavity. To test this hypothesis we determined the fasting concentrations of total, high density lipoprotein (HDL)- and low density lipoprotein (LDL)-cholesterol, apolipoprotein-A1 (apo-A1) and apolipoprotein-B (apo-B) in serum and ascites of 17 patients with cirrhosis and 16 patients with peritoneal carcinomatosis. The movement of proteins from plasma to ascites was calculated from the ascites/serum concentration ratios of six different sized proteins with a molecular mass ranging from 54 kDa to 971 kDa. Mean values (mg/dl) for total cholesterol (92.6 vs. 21.0), HDL-cholesterol (15.6 vs. 1.8), LDL-cholesterol (63.4 vs. 16.1), apo-A1 (50.2 vs. 13.6) and apo-B (41.2 vs. 12.9) in ascites were significantly higher in peritoneal carcinomatosis than in cirrhosis. These differences could only partially be explained by the higher serum concentrations of these parameters in peritoneal carcinomatosis, but were mainly due to a lower selectivity for the movement of plasma proteins and lipoproteins into ascites (mean ascites/serum (A/S) ratio: 0.30–0.77) in peritoneal carcinomatosis as compared to cirrhosis (mean ascites/serum ratio: 0.11–0.21). In both groups about 85% of the total cholesterol in serum and ascites consisted of HDL- and LDL-cholesterol. These findings support the hypothesis that elevations in ascitic cholesterol in peritoneal carcinomatosis compared to cirrhosis are mainly caused by the increased movement of plasma HDL and LDL into the peritoneal cavity

An Unusual Cause of Abdominal Ascites.

Abdominal ascites is most commonly caused by portal hypertension from liver cirrhosis. When present, portal hypertension is associated with an elevated serum-ascites albumin gradient (SAAG) ≥1.1 g/dL. In contrast, a SAAG < 1.1 g/dL suggests malignancy, tuberculosis, pancreatitis, or nephrotic syndrome. Here, we present a case of low SAAG ascites caused by epithelioid peritoneal mesothelioma in a woman with no known liver disease. The diagnosis proved elusive until diagnostic laparoscopy with biopsy was performed

Atrial natriuretic factor (ANF) and renin-aldosterone in volume regulation of patients with cirrhosis

The role of the atrial natriuretic factor and of the main counteracting sodium-retaining principle, the renin-aldosterone system, in acute volume regulation of cirrhosis of the liver has been investigated. Central volume stimulation was achieved in 21 patients with cirrhosis, 11 without and 10 with ascites, and 25 healthy controls by 1-hr head-out water immersion. Immersion prompted a highly significant (p<0.001) increase of atrial natriuretic factor plasma concentrations in cirrhotic patients without ascites from 8.5 ± 1.3 fmoles per ml to 16.5 ± 2.6 fmoles per ml, comparable to the stimulation in control subjects (6.0 ± 0.6 fmoles per ml to 13.6 ± 2.6 fmoles per ml). In cirrhotic patients with ascites, atrial natriuretic factor increase (from 7.7 ± 1.3 fmoles per ml to 11.4 ± 2.3 fmoles per ml) was blunted (p<0.05). Plasma renin activity and plasma aldosterone concentration were elevated in cirrhotic patients, especially in the presence of ascites. Following immersion, plasma renin activity and plasma aldosterone concentration were reduced similarly in all groups. Water immersion induced a more pronounced natriuresis and diuresis in control subjects than in cirrhotic patients. Neither atrial natriuretic factor nor plasma renin activity nor plasma aldosterone concentration alone correlated to sodium excretion. However, atrial natriuretic factor to plasma aldosterone concentration ratios were closely correlated to basal and stimulated natriuresis in cirrhotic patients, particularly in those with ascites. These data suggest that atrial natriuretic factor and the renin-aldosterone system influence volume regulation in patients with cirrhosis

Medical treatment of ascites in cirrhosis

Medical treatment of cirrhotic ascites is essentially supportive, dictated by the patient's discomfort, impaired cardiovascular or respiratory function and potential for infection. Treatment of ‘simple’ ascites (moderate fluid accumulation, serum albumin > 3.5 g/dl, serum creatinine < 1.5 mg/dl, no electrolyte disturbance) is implemented sequentially. Only 10% of patients respond to dietary sodium restriction and bed rest; most require pharmacotherapy consisting of spironolactone, which increases the proportion of responding patients to 65% and loop diuretics, which may produce clinical improvement in an additional 20% (85% in all); in the remaining 15% of refractory patients, use of novel adjunctive therapies may be attempted. Patients with tense ascites, impaired renal function and electrolyte disturbances merit special consideration before diuretics are introduced. Spironolactone has long been a standard for the treatment of cirrhotic ascites because it directly antagonizes aldosterone. The loop diuretic most frequently added to spironolactone has been furosemide. However, there is preliminary evidence that torasemide may be more effective in some patients. Other investigational agents that may play a role in treatment of patients resistant to conventional drugs include ornipressin (a vasopressin analogue) and atrial natriuretic factor

Ovarian Fibroma with Meigs Syndrome associated with Elevated CA125 - A Rare Case

Postmenopausal women with solid adnexal masses, ascites and pleural effusion with elevated CA 125 are highly suggestive for malignant ovarian tumor. However in literature 28 cases Meigs syndrome (Benign ovarian tumor, ascites and right pleural effusion) with raised CA 125 have been reported. We report a case of Meigs syndrome caused by right ovarian fibroma with elevated serum CA125 level in a postmenopausal woma

Ascitic fluid analysis for the differentiation of malignancy related and nonmalignant ascites

The authors tried to differentiate malignancy-related from nonmalignant ascites with a sequence of sensitive followed by specific ascitic-fluid parameters. There were four results of this study. First, of nine parameters investigated in a first series of 48 patients, 28 with nonmalignant and 20 with malignancy-related ascites, ascitic-fluid cholesterol and fibronectin yielded the best negative predictive value of 92% each. Carcinoembryonic antigen (CEA) and cytologic examination both showed a positive predictive value of 100%. Second, combining cytologic examination (sensitivity, 70%) and CEA determination (sensitivity, 45%) increased the sensitivity to 80%. Third, cytologic findings were negative in all ascitic-fluid samples with a cholesterol concentration below the cutoff value of 45 mg/100 ml. Fourth, based on the results of the first series of 48 patients, the diagnostic sequence with cholesterol as a sensitive parameter, followed by the combination of cytologic examination and CEA determination as specific parameters, was tested in a second series of 71 patients, 37 with nonmalignant and 34 with malignancy-related ascites. Again cytologic examination was negative in all samples with cholesterol levels below 45 mg/100 ml. In the total of 119 patients, this diagnostic sequence did not identify 9% of patients with malignancy-related ascites, and 82% of samples classified as malignancy related by cholesterol levels above 45 mg/100 ml were confirmed by positive cytologic examination and/or CEA level above 2.5 ng/ml. Thus, a diagnostic sequence with ascitic-fluid cholesterol determination, followed by cytologic examination and CEA determination, in samples with cholesterol levels above 45 mg/100 ml should permit a cost-efficient routine differentiation of malignancy-related from nonmalignant ascites

Struma Ovarii Associated with Pseudo- Meigs’Syndrome

Struma ovarii is a specialized ovarian teratoma composed predominantly of mature thyroid tissue. It is associated with pleural effusion and ascites (Pseudo-Meigs’ syndrome) in 5% of cases. Majorities of the strumas are benign, however occasionally malignant transformation may be seen. We report a case of a 45 years old postmenopausal woman who presented with gradually increasing dyspnoea and distention of abdomen of five months duration. USG abdomen revealed a bulky right ovary with a solid and cystic components and ascites. Her chest X-ray showed bilateral pleural effusion. Hence, clinical diagnosis of malignant ovarian tumor was kept; however, both the ascetic & pleural fluids were cytologically negative for malignant cells. The patient was operated forhysterectomy with bilateral salpingo-ophorectomy. The histopathological examination of the ovarian mass confirmed the diagnosis of struma ovarii. Postsurgical follow up of patient showed spontaneous regression of pleural effusion and ascites. The coexistence of an ovarian tumor, ascites and bilateral pleural effusion that resolves spontaneously on resection of the ovarian mass is known as pseudo-Meigs’ syndrome. Patient with pseudo-Meigs’ syndrome may present a diagnostic problem as they masquerade as carcinoma with malignant effusions. In addition, the coexistence of struma ovarii and pseudo-Meigs’ syndrome is a very rare event

Evidence for down-regulation of beta-2-adreno-ceptors in cirrhotic patients with severe ascites

The density and affinity of beta-2-adrenoceptors on mononuclear cells from peripheral blood were studied in fifteen patients with cirrhosis of different severity and in thirteen controls. There was no significant difference between cirrhotic patients and controls in density or affinity of beta-2 binding sites. Within the cirrhotic group, however, the number of binding sites per cell was significantly lower in patients with severe ascites than in patients with mild to moderate or no ascites. This down-regulation of beta-adrenoceptors could influence the haemodynamic response to beta-blockers

Hemodynamic Evaluation of Nonselective \u3b2-Blockers in Patients with Cirrhosis and Refractory Ascites

BACKGROUND:Nonselective \u3b2-blockers (NSBB) have been associated with increased incidence of paracentesis-induced circulatory dysfunction (PICD) and reduced survival in patients with cirrhosis and refractory ascites. AIM:To prospectively evaluate a hemodynamic response to NSBB in cirrhotics listed for liver transplantation with refractory ascites undergoing large volume paracentesis (LVP). METHODS:Patients with cirrhosis and refractory ascites, with an indication to start NSBB in primary prophylaxis for variceal bleeding, were enrolled. During two consecutive LVP, while being, respectively, off and on NSBB, cardiac output (CO), systemic vascular resistances (SVR), peripheral vascular resistances (PVR), and plasma renin activity (PRA) were noninvasively assessed. RESULTS:Seventeen patients were enrolled, and 10 completed the study. Before NSBB introduction, SVR (1896 to 1348\u2009dyn\ub7s\ub7cm-5; p = 0.028) and PVR (47 to 30\u2009mmHg\ub7min\ub7dl\ub7ml-1; p = 0.04) significantly decreased after LVP, while CO showed an increasing trend (3.9 to 4.5\u2009l/m; p = 0.06). After NSBB introduction, LVP was not associated with a significant increase in CO (3.4 to 3.8\u2009l/m; p = 0.13) nor with a significant decrease in SVR (2002 versus 1798\u2009dyn\ub7s\ub7cm-5; p = 0.1). Incidence of PICD was not increased after NSBB introduction. CONCLUSION:The negative inotropic effect of NSBB was counterbalanced by a smaller decrease of vascular resistances after LVP, probably due to splanchnic \u3b22-blockade. This pilot study showed that NSBB introduction may be void of detrimental hemodynamic effects after LVP in cirrhotics with refractory ascites