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Clinical assessment compared with cyst fluid analysis in the differential diagnosis of cystic lesions in the pancreas.

BACKGROUND: In adults 80% to 90% of cystic lesions in the pancreas are pseudocysts and the remainder are mostly neoplastic cysts. To choose optimal treatment for an individual patient, exact nonoperative diagnosis would be preferable. This study was done to assess the value of cyst fluid analysis, compared with clinical and radiologic findings, in the differential diagnosis of pancreatic cystic lesions. METHODS: Twenty-two patients with a cystic lesion in the pancreas underwent operation, cyst wall biopsy, and aspiration of cyst fluid. Carcinoembryonic antigen (CEA), CA 19-9, pancreatitis-associated protein (PAP), and total protein concentration, amylase activity, and cytologic findings were studied. Final diagnosis was pseudocyst in 14 patients, serous cystadenoma in two, mucinous cystadenoma in two, and mucinous cystadenocarcinoma in four patients. RESULTS: Clinical and radiologic judgment correctly differentiated pseudocysts and neoplastic cysts. Cyst fluid aspiration did not succeed in two patients with mucinous cystadenocarcinomas because of the high fluid viscosity. Cyst fluid amylase activity was high (greater than 16,000 IU/ml) in all but one pseudocyst and low (less than 83 IU/ml) in all but one neoplastic cyst. CEA level was lower in pseudocysts than in neoplastic cysts, but with an overlapping value between the groups. Mean CA 19-9 concentration was higher in pseudocysts than in neoplastic cysts, but with wide overlap between the groups. Pancreatitis-associated protein and total protein concentration and cystic fluid cytologic findings did not differ between various types of cysts. CONCLUSIONS: Clinical judgment including careful history and radiologic studies seems to be the most reliable method of differentiating neoplastic pancreatic cysts from pseudocysts. Amylase and CEA levels give suggestive information, but cyst fluid analysis may be misleading in an individual patient.

Adult↗

Radioimmunoassayable insulin-like growth factor-I in human breast cyst fluid.

insulin-like growth factor-I (IGF-I) was measured in breast cyst fluid and serum collected at the same time. In addition, epidermal growth factor (EGF) was measured in breast cyst fluid. The radioimmunoassay inhibition curve of cystic IGF-I was parallel to that of authentic IFG-I. Cystic immunoreactive IGF-I had an elution pattern similar to IGF-I from Sep-Pak C18 silica columns and from gel-filtration chromatography using Sephacryl 200. The material from Sephacryl 200 gave a radioimmunoassay curve which was parallel to IGF-I. The median (range) amount of IGF-I in cyst fluid was 9.3 ng/ml (0.8-33.3 ng/ml) and was 5-10% of that found in serum, although there was no significant correlation between the two levels. The median (range) level of cystic EGF was 416 ng/ml (14-1640 ng/ml). There was a weak negative correlation between cystic EGF and cystic IGF-I (P less than 0.01). Some women presented with multiple cysts and for these cysts there was a high degree of concordance of levels for both IGF-I or EGF. Unlike serum there was little or no protein present in cyst fluid which bound IGF-I.

Epidermal Growth Factor↗

Pancreatic cystic islet-cell tumors. Clinical and pathologic features in two cases with cyst fluid analysis.

Cystic islet-cell tumors are rare neoplasms that may be confused with more familiar cystic pancreatic lesions, such as pseudocysts, serous cystadenoma, and mucinous tumors. Analysis of aspirated cyst fluid for tumor markers (carcinoembryonic antigen [CEA], CA-125, and CA-15.3), enzymes (amylase and lipase), viscosity, and cytology has been proposed as an aid to preoperative differential diagnosis. These tests will distinguish mucinous from nonmucinous cysts and usually help in determining malignancy. However, cyst fluid parameters from rarer types of pancreatic cystic tumors have not been described. We report the clinical and pathologic features of two cystic islet-cell tumors including cyst fluid parameters in one of the cases. Two cases of cystic islet-cell tumors were identified by clinical history, histopathologic, and immunohistochemical techniques. Cyst fluid was aspirated intraoperatively from one case and analyzed for CEA, CA-125, CA 15.3, insulin, amylase, viscosity, and cytology. Cyst fluid analysis showed low values for CEA, CA-125, and CA-15.3, low viscosity, and variable amylase content. This spectrum of findings is similar to that of serous cystadenomas. Cyst fluid cytologic examination was positive for neuroendocrine-type epithelial cells and insulin levels were elevated, observations indicative of an islet-cell tumor. Analysis of fluid from cystic islet-cell tumors may aid in the preoperative differentiation of these tumors from more common pancreatic cystic lesions. These findings represent the first report of the characteristics of the fluid in these uncommon tumors.

Adenoma, Islet Cell↗

Cytotoxicity of Echinococcus granulosus cyst fluid in vitro.

In a cytotoxicity assay, using rat spleen cells as target cells, Echinococcus granulosus cyst fluid from cattle exerted a marked degree of cytotoxicity in vitro. When trypan blue exclusion or [3H]thymidine incorporation by concanavalin A stimulated spleen cells was used as a measure of cell viability, dialyzed cyst fluid showed maximum cell destruction up to a 1:8 dilution. The effect was dose and time dependent, cells being affected by 24 h after exposure to cyst fluid. The components responsible for cytotoxicity of cyst fluid were heat stable and could be recovered using gel chromatography on Sephadex G 50 and G 15 as a single low molecular weight fraction. It is assumed that the toxic products released by the living parasite can readily penetrate through the cyst wall into the surrounding host tissue. The interference of such substances with immunocompetent cells might account for the long-term survival of the parasite in the intermediate host.

Animals↗

Insulin-like growth factors and IGF binding proteins in cyst fluid from patients with craniopharyngioma prior to intracavitary irradiation with Yttrium and thereafter.

Aim-To examine a series of cyst fluid samples from patients with craniopharyngioma at various stages of treatment in order to evaluate the use of insulin-like growth factors (IGFs) and IGF binding proteins as tumour markers or indicators of successful treatment, or both.Methods-Cyst fluid samples were obtained by stereotactic puncture prior to the intracavitary application of (90)Yttrium and at subsequent occasions. Analysis was performed by gel chromatography, radio-immunoassays, binding studies, and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) with subsequent western blotting.Results-IGF-I, -II and IGF binding protein-1 concentrations were measured in three craniopharyngioma cyst fluid samples. Immunoreactive IGF-I and IGF binding protein-1 concentrations in these three samples were between 6 and 29 ng/ml, and 17 and 48 ng/ml, respectively. In contrast, the IGF-II concentrations measured in 19 cyst fluid samples from seven patients with craniopharyngioma at various stages of treatment were much higher at 25-671 ng/ml. SDS-PAGE and subsequent western blotting using [(125)I]IGF-II as the ligand gave bands with estimated molecular weights of 330, 220, 135, 96, 46, 43, 34, 29, and 13.5 kDa in one adult, and identical bands at 220, 41.5, 37.5, 32, and 19 kDa in three cyst fluid samples from three children with craniopharyngioma.Conclusions-These results suggest that IGFs and IGF binding proteins are secreted by craniopharyngiomas and that they may alter the growth characteristics of these tumours. Furthermore, the distinct pattern of IGF binding protein sizes might be used as a tool for the differential diagnosis of tumours of the central nervous system.

Journal Article↗

A study of cyst fluid and plasma carcinoembryonic antigen in patients with cystic ovarian neoplasms.

Cyst fluid and plasma carcinoembryonic antigen (CEA) levels were measured in 11 patients with ovarian cyst-adenocarcinoma and in 16 patients with benign ovarian neoplasms. In patients with ovarian cancer, plasma CEA levels were not elevated above 2.5 ng/ml unless cyst fluid CEA levels were 4 to 16 mu-g/ml. In this series, cystic and plasma CEA levels were elevated most consistently in patients with mucinous ovarian tumors. Furthermore, on the basis of molecular size and immunoreactivity by immunodiffusion, ovarian cancer cyst fluid CEA and colonic cancer CEA had similar immunochemical properties. Consistent with the findings in other neoplasms, follow-up studies showed that plasma CEA levels returned to the normal range between 2 and 12 weeks after surgical excision of the ovarian tumor. It is concluded that plasma CEA is of value in the management of patients with ovarian mucinous cystadenocarcinoma.

Carcinoembryonic Antigen↗

Quantification of epidermal growth factor in human breast cyst fluids: correlation with dehydroepiandrosterone-sulphate and electrolyte concentrations.

Epidermal growth factor (EGF), dehydroepiandrosterone (DHA)-sulphate and [Na+] and [K+] were assayed in 78 cyst fluids from patients with a palpable breast cyst. Epidermal growth factor was detected in all but 2 cysts, the mean value +/- SEM being 506.2 +/- 39.3 ng/ml, with a range of 0-1,599 ng/ml. When the cyst fluids were sub-divided according to their [Na+]:[K+] ratio, group A cyst fluids ( [Na+]:[K+] less than 3) had a significantly higher (p less than 0.001) level of EGF than group B cyst fluids ([Na+]:[K+] greater than 3). Furthermore, the relationship between EGF and [Na+] and [K+] and between EGF and DHA-sulphate seemed to differ between the 2 cyst types and each cyst type was therefore analyzed separately.

Aged↗

Vascular endothelial growth factor levels in ovarian cyst fluid correlate with malignancy.

Ovarian cancer is a richly vascularized neoplasm with solid and cystic components. The purpose of this study was to determine whether cyst fluid could be used to quantitatively evaluate production of angiogenic factors in ovarian lesions. ELISA was used to measure vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the cyst fluid of patients with ovarian cancer (n = 13), benign cysts and cystadenomas (n = 23), borderline tumors (n = 5), and functional cysts (n = 8). VEGF levels were markedly elevated in the fluid of malignant cysts (38.5+/-8.2 ng/ml) as compared with benign (1.6+/-0.4 ng/ml; P < 0.001), borderline (5.7+/-1.5 ng/ml; P < 0.001), or functional cysts (3.8+/-2.0 ng/ml; P < 0.001). The presence of VEGF in cancer cells was confirmed by immunohistochemistry. Follow-up of patients with malignant and borderline lesions demonstrated a correlation between VEGF levels in cyst fluid and tumor recurrence (P = 0.03). bFGF in malignant cysts was either undetectable or very low (0.3+/-0.2 ng/ml), and no significant differences were found in bFGF levels among malignant, benign, borderline, and functional cysts. This study demonstrates that ovarian malignancy is associated with dramatic elevation of VEGF levels in ovarian cyst fluid. Conversely, there is no correlation between cyst fluid bFGF levels and malignant transformation. The high levels of VEGF in malignant cysts are consistent with the hypothesis that this growth factor plays an important role in ovarian cancer related-angiogenesis and tumor progression and represents a potentially important target of antiangiogenic therapy.

Adult↗

Measurement of pS2 protein in pancreatic cyst fluids. Evidence for a potential role of pS2 protein in the pathogenesis of mucinous cystic tumors.

CONCLUSION: Elevated levels of the growth factor pS2 protein in the cyst fluids of mucinous cystic tumors correlate with earlier observations using immunohistochemical techniques showing that pS2 protein is expressed by these tumors. The markedly elevated levels of pS2 protein compared to normal plasma values suggest that this growth factor may be important in the pathogenesis of pancreatic mucinous cystic tumors. BACKGROUND: Cystic lesions of the pancreas include inflammatory pseudocysts, serous cystadenomas, and mucinous cystic tumors, some of which are malignant. Previous studies using immunohistochemical techniques have shown that virtually all pancreatic mucinous tumors express pS2 protein. pS2 protein is a growth factor that is believed to be important in the normal process of inflammation and repair. We measured pS2 protein and other growth factors in pancreatic cyst fluids to assess their potential pathophysiologic and diagnostic significance. METHODS: Levels of pS2 protein were measured in 54 pancreatic cyst fluids by radioimmunoassay. The growth factors, epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and insulin-like growth factors I and II (IGF-I, IGF-II) were measured in 22 cyst fluids using commercial immunoassays. RESULTS: Mucinous cysts exhibited significantly higher levels of cyst fluid pS2 protein than nonmucinous lesions, including pseudocysts and serous cystadenomas (median: 78,303 pg/mL; range: 218-361,176 pg/mL vs median: 886 pg/mL; range: 0-14,206 pg/mL; p = 0.0001). The level of pS2 in mucinous tumors was markedly higher than plasma values (median: 392 pg/mL). Levels of pS2 protein in malignant mucinous lesions tended to be higher than those in benign mucinous cysts, but this difference was not statistically significant (median: 88,817 vs 64,350 pg/mL; p = 0.159). Levels of other growth factors, including EGF, TGF-alpha, IGF-I, and IGF-II, did not discriminate among the different cyst types, and the values were within normal plasma ranges.

Cyst Fluid↗

Identification and diagnostic value of a major antibody epitope on the 12 kDa antigen from Echinococcus granulosus (hydatid disease) cyst fluid.

An IgG1 monoclonal antibody (MoAb), designated C9E7H8, has been produced against an epitope on the 12 kDa antigen of Echinococcus granulosus cyst fluid, believed to represent the smallest subunit of antigen B. This MoAb, raised against purified 12 kDa antigen eluted from a reducing SDS-PAGE gel, demonstrated strong binding to native sheep cyst fluid in ELISA and recognition of all three subunits of antigen B (at 12, 16, 23 kDa) by immunoblot under both reducing and non-reducing conditions. Immunoblot analysis also indicated that the complementary epitope is conserved amongst cyst fluids from different intermediate hosts of E. granulosus, including fluids from cysts of two distinct strains, and is present in cyst fluid from E. multilocularis. The monoclonal displays binding to a cDNA clone, EgPS-3, which we have previously shown expresses part of the 12 kDa molecule. EgPS-3, expressed as a glutathione-S-transferase fusion protein, was successful in positive detection of 74% of cystic hydatid patients, although cross-reactions were observed with 25% of sera from alveolar hydatid and 22% of sera from schistosomiasis japonica patients. Three peptides, based on the predicted amino acid sequence of EgPS-3, showed increased specificity but slightly reduced sensitivity in the detection of antibody from E. granulosus patients. The predominant epitope recognized by human antibody occurs in the N-terminal 27 amino acids (peptide 65) of EgPS-3 which also correlates with the location of the monoclonal antibody epitope.

Amino Acid Sequence↗

Cancer-associated antigen CA 195 in patients with mucinous ovarian tumours: a comparative analysis with CEA, TATI and CA 125 in serum specimens and cyst fluids.

The CA 195 levels in ovarian cyst fluids from malignant mucinous tumours (median 2,300,000 U/ml) were significantly higher than the levels in benign mucinous tumours and malignant non-mucinous tumours (medians of 26,800 and 1,700 U/ml, respectively, p = 0.039 and 0.011). Also, the carcinoembryonic antigen (CEA) and tumour-associated trypsin inhibitor (TATI) levels in cyst fluid from mucinous tumours were much higher than those in non-mucinous tumours. Pretreatment serum CA 195 levels were found to be elevated (> 10.5 U/ml) in 72% of the patients with malignant mucinous tumours (n = 25), compared with 35% in malignant non-mucinous tumours and 28% in benign mucinous tumours. The positivity rate shown for serum CA 195 in malignant mucinous tumours was higher than that measured for serum TATI, CA 125 or CEA (60, 53 and 42%, respectively). Measurement of serum CA 195 can be valuable in the clinical management of patients with mucinous ovarian cancer.

Adenocarcinoma, Mucinous↗

Androgen conjugates in human breast cyst fluids.

Dehydroepiandrosterone sulfate (DHAS) has been measured by radioimmunoassay in 100 breast cyst fluids obtained from 82 women. Values ranged from 1.5 to 1,155 microM with a median of 140 microM. These concentrations are in excess of those for plasma but are comparable or less than values for breast secretions obtained by nipple aspiration. Levels of DHAS in cyst fluid were not significantly affected by age, menopausal status, or parity of the subject or by the volume of cyst fluid obtained. In patients with multiple cysts, DHAS values from cysts aspirated from the same breast on the same data were relatively comparable, but wide variations were frequently observed between cysts aspirated on different occasions from the same breast and between cysts from different breasts of the same patient, whether sampled simultaneously or sequentially. Such variability must complicate comparative studies among women.

Adult↗

Immunoproteins in human brain tumor cyst fluids.

Quantitation of the concentration of immunoproteins in serum, and cystic fluids from six patients (three with cerebral astrocytoma and three with cerebellar hemangioblastoma) has been determined. The values for total protein, albumin, immunoproteins IgG, IgA, and IgM, and C3C (complement) in cyst fluid more closely correspond to serum than to cerebrospinal fluid values. Values for cyst fluid, cerebrospinal fluid, and serum were determined using albumin ratios in order to compare relative differences between fluids from these three compartments. Our data suggests that: 1) the major protein content of brain tumor cyst fluid is consequential to a transudative process from serum, and 2) that immunoglobulins IgG and IgA are present in higher concentrations in human brain tumor cyst fluids in comparison to IgM concentrations. These studies further question the concept of the brain as an "immunological privileged site", and may be of direct relevance to the investigation of the use of immunotherapeutic modalities as an adjunct after surgical tumor removal.

Adolescent↗

[The comparison of CA-125 and CEA levels in serum and ovarian cyst fluid in girls and young women].

OBJECTIVES: The aim of the study was to compare the CA-125 and CEA levels in serum and ovarian cyst fluid. MATERIALS AND METHODS: Concentration of the CA-125 and CEA were measured at 12 girls and young women with benign, low malignant potential and functional cysts hospitalized in our teaching department. Concentrations were measured using immunoenzymatic method. RESULTS: We did not observe any difference in serum levels of CA-125 and CEA between neoplastic and functional cysts. On the contrary we found very high levels of the markers in the neoplastic cyst fluid in comparison with the functional ovarian cyst fluid. CONCLUSION: It seems that high levels of the CA-125 and CEA in neoplastic cyst fluid in comparison with functional may be useful in differential diagnosis.

Adolescent↗

[Hydatid cyst fluid (Echinococcus granulosus) biochemistry. Influence of site on cyst permeability].

Eleven metabolites were determined in 19 hydatid cyst fluids of variable size and localization, and in patients plasma before surgery. Specific indirect immunofluorescent antibody titration was carried out. Sodium (132 +/- 5.2 mmol/l), chloride (92.9 +/- 6.5 mmol/l) and bicarbonate (22.1 +/- 1.5 mmol/l) were found at the same concentration than in plasma. Potassium (5.4 +/- 0.3 mmol/l) and calcium levels (4.7 +/- 0.9 mmol/l) were higher than in plasma, and phosphate (0.1 +/- 0.03 mmol/l) decreased tenfold. Glucose (3.4 +/- 0.8 mmol/l), creatinine (39.3 +/- 7.2 mumol/l) and urea nitrogen (4.6 +/- 0.8 mmol/l) showed great variations. Cholesterol levels 0.06 +/- 0.03 mmol/l) were a hundredfold lower than in plasma. Total protein levels (0.34 +/- 0.09 g/l) were found at very low concentrations. Extra-pulmonary cysts showed significantly higher antibody titers than pulmonary cysts. No correlation was observed between the size of the cysts and the level of the immune response. Significant difference about the relative cholesterol concentration (cystic concentration/plasmatic concentration) was observed between pulmonary and extra-pulmonary cysts (respectively 0.0048 +/- 0.0032 and 0.018 +/- 0.01--p less than 0.05). No correlation was observed between the size of the cyst, or the corresponding levels of the immune response, and the cholesterol levels. The hypothesis of a greater membrane permeability in extra-pulmonary cyst is discussed.

Antibodies↗

Partial purification and comparison of the kinetic properties of ovine liver Echinococcus granulosus hydatid cyst fluid malate dehydrogenase and the cytoplasmic enzyme from the host liver.

Ovine liver Echinococcus granulosus hydatid cyst fluid and cytoplasmic healthy ovine liver malate dehydrogenases were purified 24- and 30-fold by Sephadex G-200 and DEAE-Sephadex chromatography. Both enzymes were eluted with the same elution volume and the same salt concentration from the respective columns. The pH optimum of the enzymes from both sources was 8.4 in either Tris-HCl or barbital buffer. The Km values for oxaloacetate were 0.211 and 0.200 mM for hydatid cyst fluid and healthy ovine liver enzymes, respectively. The Km values for NADH were 0.220 and 0.213 mM for hydatid cyst fluid and healthy ovine liver enzymes, respectively. Enzyme from both sources demonstrated similar heat denaturation patterns. Both enzyme preparations were inhibited at high concentrations of either substrate. Neither enzyme was inhibited by para-hydroxymercuribenzoate or fumarate, and both enzyme preparations were specific for NADH as a cofactor. The results are discussed in terms of the possible infiltration of the host enzyme into the cyst fluid.

Animals↗

Levels of human chorionic gonadotropin in breast cyst fluid.

The results of dosage of human chorionic gonadotropin (HCG) in 75 breast cyst fluids taken from 61 patients suffering from breast gross cystic disease (BGCD), 13 of which had multiple mono and/or bilateral cysts are discussed. The corresponding sera were also examined. Assays were carried out using the ELISA method. For comparison, HCG levels were also determined in 21 breast cyst fluids using RIA method. In 66.7% of the breast cyst fluids examined the hormone levels were higher than normal serum values. Corresponding sera showed HCG to be within the range of normal levels. In 5 patients the multiple and/or bilateral cysts showed widely differing hormone levels. The importance of these observations is discussed.

Adolescent↗

Echinococcus granulosus: occurrence of ecdysteroids in protoscoleces and hydatid cyst fluid.

Both free ecdysteroids and hydrolysable polar conjugated ecdysteroids were detected in protoscoleces of Echinococcus granulosus from the equine host, and in hydatid cyst fluid from the same source. Comparisons were made of hydatid cyst fluid from E. granulosus infections of three intermediate host species: horses, sheep and humans. Ecdysone and 20-hydroxyecdysone were identified in both protoscoleces and hydatid cyst fluids by high-performance liquid chromatography monitoring fractions by radioimmunoassay, and by capillary gas chromatography/mass spectrometry (selected ion monitoring). The free ecdysteroid fractions of hydatid cyst fluid from horses and sheep also contained several unidentified, chromatographically unique, immunoreactive compounds which were refractory to hydrolysis with a crude Helix pomatia aryl sulphatase enzyme preparation.

Animals↗