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[Endocrinously active parathyroid cysts. Their diagnosis by the determination of intact parathormone in the cyst fluid].

A 53-year-old woman with recurrent nephrolithiasis was found to have hypercalcaemia of 3.12 mmol/l and an intact parathormone level of 166 pg/ml, indicating primary hyperparathyroidism. Preoperative ultrasound examination to localize the parathyroid adenoma revealed a clear fluid-containing cyst in the right lobe of the thyroid. The aspirated fluid had an intact parathormone level of 306 pg/ml, twice that in serum. The cyst was removed surgically. 14 days postoperatively calcium and parathormone levels in serum had become normal without any calcium administration. Measuring the concentration of intact parathormone in the aspirated cyst fluid made possible not only the distinction from a thyroid cyst but also the precise preoperative localization of the parathyroid cyst.

Body Fluids↗

Cyst fluid analysis in the differential diagnosis of pancreatic cysts: a new approach to the preoperative assessment of pancreatic cystic lesions.

Pancreatic cysts include pseudocysts, serous tumors, and mucinous tumors, some of which are malignant. The clinical and radiologic features of these lesions may not permit a preoperative diagnosis. Analysis of percutaneous cyst fluid aspirates for cytologic findings, tumor markers, enzymes, and viscosity has been proposed as an aid to differential diagnosis. The combination of cytologic findings, carcinoembryonic antigen level, and viscosity will usually differentiate mucinous from nonmucinous cysts, whereas cytologic findings and levels of tumor markers CA 15-3 and CA 72-4 are useful to predict malignancy. Pseudocysts can be identified by a combination of cytologic features; levels of tumor markers, including NB/70K; and levels of enzymes, including amylase isoenzymes and leukocyte esterase. Serous tumors are a diagnosis of exclusion, although in 50% of cases the cytologic findings will indicate a serous tumor. When compared with conventional methods of differentiating pancreatic cysts, cyst fluid analysis is a promising new approach to the evaluation of these diagnostically difficult lesions.

Amylases↗

Accumulation of hormones in breast cyst fluid.

The concentration of some immunoreactive peptide hormones in breast cyst fluid and serum from a series of patients with cystic breast disease were compared. The concentrations of the two pituitary gonadotropins, LH and FSH, were consistently higher in serum than in cyst fluid, confirming earlier more limited observations. The mean PRL concentration, on the other hand, was elevated in cyst fluid though the variability was great. The cyst fluid serum ratio of hCG was elevated in the patient group as a whole. However, the results suggested the presence of two subpopulations; group I, in which the cyst fluid and serum hCG levels were essentially indistinguishable and in the range found in normal serum, and group II, in which the cyst fluid hCG concentration was consistently greater than the normal serum range. Analysis of hormone concentrations in multiple cysts aspirated at the same time showed a remarkable degree of agreement in the cyst hormone levels in most of the patients. The greatest variability in the levels was seen with hCG, were a small numer of subjects showed a very large spread in the values.

Breast Diseases↗

Cyst fluid from a murine model of polycystic kidney disease stimulates fluid secretion, cyclic adenosine monophosphate accumulation, and cell proliferation by Madin-Darby canine kidney cells in vitro.

Cyst fluids from subjects with autosomal dominant polycystic kidney disease (ADPKD) cause polarized monolayers of MDCK cells to secrete fluid toward the apical compartment in vitro. To determine the extent to which secretagogue accumulation may be a general feature of polycystic diseases, cyst fluid from mice with a slowly progressive form of hereditary PKD (DBA/2FG-pcy/pcy) was added to polarized MDCK monolayers. Basolateral application of cyst fluids (diluted with culture medium to 15% final concentration) from 13 different animals 16 to 35 weeks old increased the fluid secretion rate from a baseline of 0.023 +/- 0.003 to 0.111 +/- 0.017 microL/cm2/h (P < 0.005). There was a direct relation between the concentration of cyst fluid and the rate of net fluid secretion. The secretory activity of cyst fluid was not altered by pronase treatment or boiling. Cyst fluid (10%) added to the basolateral surfaces of polarized MDCK monolayers for 24 hours increased cell cyclic adenosine monophosphate (AMP) levels from a baseline of 6.3 +/- 0.2 to 17.3 +/- 0.3 pmoles/monolayer (n = 3, P < 0.05). The capacity of cyst fluid to increase cyclic AMP levels was not changed by pronase treatment or boiling. There was a direct relation between the level of cellular cyclic AMP and the rate of transepithelial fluid secretion caused by cyst fluid. Cyst fluid increased thymidine incorporation by Madin-Darby canine kidney (MDCK) cells to an extent equal to that caused by epidermal growth factor and caused MDCK cells to form cysts in collagen matricies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The role of pancreatic cyst fluid molecular analysis in predicting cyst pathology.

BACKGROUND & AIMS: Current methods to detect malignancy in mucinous cystic neoplasms of the pancreas remain inadequate. The role of detailed molecular analysis in this context was investigated. METHODS: Endoscopic ultrasound-guided pancreatic cyst aspirates were prospectively collected during a period of 19 months and studied for cytology, carcinoembryonic antigen level, and molecular analysis. Molecular evaluation incorporated DNA quantification (amount and quality), k-ras point mutation, and broad panel tumor suppressor linked microsatellite marker allelic loss analysis by using fluorescent capillary electrophoresis. The sequence of mutation acquisition was also calculated on the basis of a clonal expansion model, and comparison was made to the final pathology. RESULTS: Thirty-six cysts with confirmed histology were analyzed. There were 11 malignant, 15 premalignant, and 10 benign cysts. Malignant cysts could be differentiated from premalignant cysts on the basis of fluid carcinoembryonic antigen level (P=.034), DNA quality (P=.009), number of mutations (P=.002), and on the sequence of mutations acquired (P<.001). Early k-ras mutation followed by allelic loss was the most predictive of a malignant cyst (sensitivity, 91%; specificity, 93%). CONCLUSIONS: Malignant cyst fluid contains adequate DNA to allow mutational analysis. A first hit k-ras mutation followed by allelic loss is most predictive of the presence of malignancy in a pancreatic cyst. This approach should serve as an ancillary tool to the conventional work-up of pancreatic cysts. Cumulative amount and timing of detectable mutational damage can assist in diagnosis and clinical management.

Carcinoembryonic Antigen↗

[Lipid peroxidation in the cyst fluid of craniopharyngiomas].

Comparing of the craniopharyngiomas cyst fluid, collected during the surgery, with blood plasma revealed significantly enhanced lipid peroxidation and lactate accumulation in tumour cysts contents. These processes were usually more prominent in endosuprasellar than in suprasellar craniopharyngiomas. The maximum of free radical formation in conjunction with the lowest level of malondialdehyde (MDA) was observed in primary tumours with relatively high proliferation rate. Controversial parameters ratio characterised the recurrent craniopharyngiomas, and in cyst fluids of the primary tumours with low proliferation rate the medium parameter's values were observed. Thus, the estimation of free radical formation level and MDA concentration in cyst fluid of craniopharyngioma seems to be prognostic for the tumour recurrence.

Adolescent↗

Relationships of Na+ and K+ concentrations to GRP, CGRP, and calcitonin immunoreactivities and Na+,K(+)-ATPase (NKA) inhibitory activity in human breast cyst fluid.

BACKGROUND: Although the etiology of gross cystic disease of the breast is unknown, elevated cyst concentrations of potassium (K+) (> 60 mM/L) may be related to symptoms. The purpose of this study was to clarify the mechanism(s) of K+ accumulation in breast cysts. METHODS: We assayed cyst fluids for factors known to exert effects on K+ transport, namely, endogenous digitalis-like inhibitors of Na+,K(+)-ATPase (NKA) and the neuropeptides gastrin-releasing peptide (GRP), calcitonin (CT), and calcitonin gene-related peptide (CGRP). RESULTS: Cyst fluid K+ was directly correlated with cyst volume, cyst NKA inhibitory activity (in ouabain equivalents), and cyst concentrations of calcitonin, GRP, and CGRP. Cyst fluid Na+ was inversely correlated with cyst fluid K+, cyst NKA inhibitory activity, cyst volume, and cyst fluid concentrations of calcitonin, GRP, and CGRP. NKA inhibitory activity correlated directly with GRP and CGRP. Immunocytochemistry localized GRP to breast cyst lining cells and areas of ductal and lobular epithelial hyperplasia in biopsies of 15 of 15 cysts and in 5 of 5 breast carcinomas, but not in (0 of 5) normal breast biopsies. Specificity of GRP staining was demonstrated by total abolition of reactivity after adsorption with synthetic GRP, but not after adsorption with synthetic substance P, neurokinin A, or neurokinin B. CONCLUSIONS: We conclude that both the concentrations of endogenous digitalis-like factors and the neuropeptides calcitonin, GRP, and CGRP in human breast cyst fluids are related to the concentrations of K+ and Na+ in breast cysts and to cyst volume.

Adult↗

Biochemical analysis of thyroid cyst fluid obtained by fine-needle aspiration.

Despite the relatively ready availability of thyroid cyst fluid specimens, little has been published on their biochemical composition. We measured the concentrations of 18 analytes in thyroid cyst fluid specimens from benign (n = 17) and malignant (n = 3) lesions and in homogenates of normal thyroid tissue (n = 5). The concentrations of an additional five analytes were measured in selected cyst fluid specimens only. Compared with normal human serum specimens, we found that in thyroid cyst fluid specimens the activities of acid phosphatase, aspartate aminotransferase, amylase, and lactate dehydrogenase, and the concentrations of iron and total bilirubin were highly increased. The concentration of glucose was low. The gross appearance of the fluids and the presence of certain analytes were consistent with a hemorrhagic origin of most of the benign and malignant cyst fluid specimens. Other biochemical markers, however, indicated colloidlike features and/or an admixture of thyroid tissue components to the cyst fluid. Although we have limited data for cyst fluid specimens from malignant thyroid lesions, we found no evidence that the results of any of the common biochemical tests would distinguish benign from malignant lesions.

Biopsy, Needle↗

Free amino acid concentration in hydatid cyst fluids from fertile and infertile human and animal Echinococcus granulosus.

The aim of this study was to search and compare free amino acid composition of fertile and infertile cyst fluids obtained from humans and animals infected naturally with Echinococcus granulosus, by using automated analysis based on cation-exchange chromatography with post-column ninhydrin derivatization system. 11 free amino acids from fertile (sheep origin), nine from infertile (cattle origin), 13 from infertile (human origin) hydatid cyst fluids and 19 amino acids from sera of patients with hydatid infection were detected. The levels of glycine, alanine, valine and lyrosine in fertile and infertile hydatid cysts fluids were significantly higher than in sera from patients with hydatid cysts. Glycine level in the fertile hydatid cyst fluids (sheep origin) was significantly higher than those of infertile cysts fluids (cattle and human origin) and sera with hydatid patients. Glycine level in fertile hydatid cyst fluids was about two times more concentrated in infertile cattle cyst fluids, 10 times more concentrated in infertile human hydatid cyst fluids and 13 times more concentrated in sera with hydatid patients. On the other hand, alanine and valine concentration in the fertile and infertile cyst fluids were at similar level with the exception that valine level in fertile cyst fluids was 12 times more concentrated in infertile human cyst fluids. The levels of tyrosine, citrulline, leucine, isoleucine and lysine amino acids in fertile and infertile hydatid cyst fluids were similar. Our findings with respect to fertile and infertile cysts fluids showed that free amino acids concentrations in cyst fluids were significantly, higher in sera from patients with hydatid cyst. Total amount of free amino acids content in fertile and infertile cyst fluids was three to eight times higher from that of human sera with hydatid patients.

Amino Acids↗

Vascular endothelial growth factor in ovarian cyst fluid.

BACKGROUND: The purpose of the current study was to determine vascular endothelial growth factor (VEGF) concentrations in cyst fluid from malignant, borderline, and benign ovarian tumors, and to correlate these data with preoperative serum VEGF concentrations and clinicopathologic characteristics. METHODS: One hundred seven ovarian cysts were removed and punctured for cyst fluid collection. Histologic diagnosis revealed 25 malignant, 12 borderline, and 70 benign ovarian tumors. The VEGF concentrations of all the cyst fluid specimens as well as in 37 preoperatively collected serum samples were determined by making use of a sandwich type double determinant enzyme linked immunoadsorbent assay based on a combination of 4 polyclonal antibodies. RESULTS: Statistically significantly higher VEGF concentrations were found in cyst fluid from malignant (median, 21.5 microg/L) compared with borderline (median, 3.2 microg/L; P = 0.01) or benign tumors (median, 1.3 microg/L; P < 0.0001). Preoperative serum VEGF concentrations were significantly higher in patients with malignant (median, 0.63 microg/L; range, 0.016-17.7 microg/L) compared with nonmalignant tumors (median, 0.28 microg/L; range, 0.016-0.89 microg/L; P = 0.008). A significant correlation of preoperative serum VEGF was found with VEGF cyst fluid concentrations (r = 0.38; P = 0.02). Significantly higher VEGF cyst fluid concentrations were found in serous malignant (median, 31.9 microg/L) compared with mucinous malignant tumors (median, 4.7 microg/L; P = 0.004). Not significant, though higher median VEGF cyst fluid concentrations were found in advanced International Federation of Gynecology and Obstetrics (FIGO) Stage II, III, and IV, histologic Grade 2 and 3, patients with residual tumor greater than 2 cm, with malignant cells in ascites or peritoneal washings, or with recurrent disease, as compared with FIGO Stage I, histologic grade 1, patients with less than or equal to 2-cm residual tumor, without malignant cells in ascites/peritoneal washings, or without recurrent disease, respectively. CONCLUSIONS: It has become clear from the increased study sample that ovarian tumors of different histologic etiology vary in VEGF cyst fluid concentrations, with the highest VEGF cyst fluid concentrations in malignant tumors. The prognostic significance of VEGF cyst fluid concentrations in advanced FIGO stage seems to be of limited value but may be important in the selection of high risk FIGO Stage I and borderline types. Data from this study indicate a possible role for VEGF as a serum tumor marker.

Adenocarcinoma, Mucinous↗

Effects of chocolate cyst fluid on endometrioma cell growth in culture.

OBJECTIVE: To evaluate the effect of chocolate cyst fluid on the proliferation of cultured human endometrioma cells and to assay the concentration of transforming growth factor-B1 in this fluid. DESIGN: Controlled in vitro study. SETTING: Department of Obstetrics and Gynecology, State University of New York Health Science Center. PATIENT(S): Five women with ovarian endometriomas. INTERVENTION(S): Endometrioma tissue and chocolate fluid from five different patients were entered in this study. MAIN OUTCOME MEASURE(S): Endometrioma cell proliferation in culture with and without chocolate cyst fluid. RESULT(S): Chocolate cyst fluid increased the proliferation of endometrioma cells compared with controls. Also, high concentrations of transforming growth factor-B1 were found in cysts' fluid. CONCLUSIONS: Chocolate cyst fluid has a growth-enhancing effect on endometrioma cells. One promoting growth factor is transforming growth factor-B1.

Cell Count↗

Cyst fluid levels of carcinoembryonic antigen, carbohydrate antigen 19-9, squamous cell carcinoma antigen, and amylase in thyroglossal duct and branchial cleft cysts.

Cyst fluid was aspirated from five thyroglossal duct cysts (TDCs) and four branchial cleft cysts (BCCs). The cyst fluid levels of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, squamous cell carcinoma antigen (SCC), and amylase were measured and compared between the two types of cyst. The enzyme immunoassay technique was used for CEA and CA19-9, while SCC and amylase levels were measured by the immunoradiometric assay and nitrophenol method, respectively. Immunostaining for CEA, CA19-9, and amylase was also performed. The serum levels of these markers in both groups of patients were within the normal ranges. In contrast, their cyst fluid levels were extremely high. There was no significant difference in the cyst fluid levels of CEA and SCC between the two types of cyst; however, the cyst fluid from the TDCs showed significantly higher levels of CA19-9 and significantly lower levels of amylase compared with that from the BCCs. Immunostaining revealed expression of CA 19-9 in nearly half the columnar epithelial cells in the TDCs, but not in the squamous epithelial cells in the BCCs. CEA and amylase were not found in the epithelial cells of either type of cyst. These findings seem to reflect the difference in etiology between TDCs and BCCs.

Adult↗

Organochlorine compounds (DDE and PCB) in plasma and breast cyst fluid of women with benign breast disease.

The organochlorines, dichloro-diphenyl-trichloroethane and polychlorinated biphenyl (PCB) are pervasive environmental contaminants. Results from previous studies have been conflicting regarding the relationship between the internal dose of these organochlorine residues and breast cancer risk. To determine whether these compounds are present in breast cyst fluids and whether cyst fluid and plasma concentrations are correlated, we analyzed organochlorines in paired cyst fluid and plasma samples from 24 subjects using gas chromatography and electron capture detection. All but one of the women had a history of multiple cysts, suggesting that they were at elevated risk for future breast cancer. DDE (a metabolite of dichloro-diphenyl-trichloroethane) was present in 22 of the cyst samples and PCB was detected in 19 of the cyst samples. Organochlorine levels were more concentrated in the plasma than in breast cyst fluids. Levels of DDE in plasma were significantly correlated with those in cyst fluid (r = 0.73; P < 0.001); in contrast to PCB levels in cyst and plasma (r = 0.37; P = 0.12). Congener specific analysis of the PCBs showed that some individual congeners were preferentially excluded from or concentrated in the cyst fluid. To our knowledge, this study is the first to demonstrate that PCB and DDE are present in cyst fluids and thus in contact with the ductal epithelium of the breast. These results support the use of plasma DDE as a proxy for DDE in the target tissue in research on the role of environmental factors in breast cancer.

Adult↗

Glutathione S-transferases P1-1 and A1-1 in ovarian cyst fluids.

PURPOSE: The purpose of the present study was to determine the gluthathione S-transferases (GST) P1-1 and A1-1 levels in cyst fluid from malignant, borderline, and benign ovarian tumors. The clinical relevance of these enzymes in cyst fluid was investigated, including the possible relation with resistance to chemotherapy. METHODS: A total of 90 ovarian cysts were punctured for cyst fluid collection. GSTP1-1 and GSTA1-1 concentrations were determined by ELISA in cyst fluid from 23 malignant, 9 borderline, and 51 benign primary ovarian tumors, and levels were correlated with histopathological data. RESULTS: Significantly higher GSTP1-I concentrations were found in cyst fluid from malignant (median: 477 ng/ml), compared with benign (median: 52 ng/ml) ovarian cysts (p < 0.0001), as well as in fluid from borderline (median: 366 ng/ml) compared with benign cysts (p < 0.0001). No significant differences were found in cyst fluid GSTA1-1 concentrations between the histologic subgroups. In cyst fluid from malignant tumors higher GSTPI-1 and lower GSTAI-1 concentrations were found in patients with worse prognostic factors: FIGO II-III-IV, grade 2-3, residual tumor > 2 cm, presence of ascites, patients with recurrent disease, and survival, but differences were not significant. In the subgroup of patients that received cisplatin-based chemotherapy (n = 14) significantly higher GSTP1-1 (p = 0.01) concentrations were found in patients with recurrence compared with patients without recurrence. Considering only FIGO stage I patients, a differentiation could be made between patients with or without recurrence based on cyst fluid GSTP I - I concentrations. CONCLUSIONS: Determination of glutathione S-transferases P 1-1 in cyst fluid samples from ovarian tumors can be of additiona] value in the differentiation between histologic subgroups. In case of possible low malignant potential cysts where sampling of the most representative tissue can be an issue, determination of GSTP- I concentrations in cyst fluid may optimise histopathologic classification. Cyst fluid GSTP1-1 seems to be a good marker for aggressiveness of the ovarian tumor, and it may predict response to chemotherapy.

Adult↗

Prostate specific antigen molecular forms in breast cyst fluid and serum of women with fibrocystic breast disease.

We have analyzed matched serum and breast cyst fluid samples for total PSA from 148 patients with fibrocystic breast disease. We have also determined the molecular forms of PSA (free PSA and PSA bound to alpha1-antichymotrypsin) in 78 breast cyst fluid samples. We found that total PSA can be detected in all cyst fluids and in about 75% of female sera. The median total PSA concentration in breast cyst fluid (bcf) is about 30 times higher than the median in the corresponding sera. Breast cyst fluid and serum PSA are not correlated with each other. Total serum PSA is inversely associated with patient age but the inverse association between bcf PSA and age is weak. Lower total PSA in bcf was seen in women who breast feed, and higher bcf PSA is associated with multiple cysts. Type I cysts (with a high K+/ Na+ ratio) tend to have higher total PSA than Type II cysts. All but three of the fractionated cyst fluids (75/78; 96%) had free PSA as the predominant molecular form. The most consistent finding of our study was the positive association between the cyst fluid K+/Na+ ratio and the free to bound PSA ratio. This association was confirmed by Spearman correlation as well as by Wilcoxon and chi-square analysis. Secretory/apocrine cysts (Type I) tend to have more total PSA and proportionally more free PSA than transudative/flattened cysts (Type II).

Adult↗

The chemotactic cytokine interleukin-8--a cyst fluid marker for malignant epithelial ovarian cancer?

Due to the difficulties in separating malignant and benign ovarian cysts by transvaginal ultrasound and other techniques, there is a need for biochemical markers in serum or cyst fluids. In the present study we have evaluated the levels of the chemokine interleukin-8 (IL-8) in ovarian cysts. IL-8 is known to be expressed in the normal ovary and to influence proliferation and angiogenesis of several nonovarian types of tumors. Cyst fluids from benign (n = 15) and malignant (n = 13) ovarian tumors were analyzed. The levels of IL-8 were found to be significantly (13-fold) higher in cyst fluids from malignant tumors (18.1 +/- 7.5 ng/ml; mean +/- SE) compared to benign cysts (1.3 +/- 0.7 ng/ml). The plasma levels of IL-8 were considerably lower (2.9 and 0.3% of levels in benign and malignant cyst fluids, respectively) than in cyst fluids. No difference in the plasma levels of patients with benign or malignant tumor could be detected. In contrast, the levels of CA 125 were significantly higher in plasma of patients with malignant disease with the inverse relation in cyst fluids. In conclusion, the levels of IL-8 are markedly elevated in cyst fluid from malignant tumors compared to benign. This specific increase indicates a role for this cytokine in ovarian tumor biology.

Biomarkers, Tumor↗

Tumour-associated trypsin inhibitor (TATI) in human ovarian cyst fluid. Comparison with CA 125 and CEA.

The levels of tumour-associated trypsin inhibitor (TATI), CA 125 and CEA were measured in ovarian cyst fluids from 21 patients. TATI in cyst fluid was immunologically and physicochemically similar to the peptide originally isolated from the urine of a patient with ovarian cancer. Mucinous cysts contained significantly higher levels of TATI than did serous cysts. Immunohistochemically TATI was localized in the apical parts of cells of mucinous ovarian cysts. These results suggest that this tumour-associated peptide is actually produced by a tumour. Like TATI, CEA occurred at higher concentrations in mucinous than in serous cyst fluids, whereas CA 125 was found in higher concentrations in serous than in mucinous cyst fluids. The concentrations of these tumours markers in cyst fluids did not correlate with circulating levels of the same markers. In spite of the very high levels of all these tumour markers in benign cyst fluids, serum levels were normal or only slightly elevated. Clearly elevated serum levels occurred only in patients with malignant tumours. Cyst fluid levels of these tumour markers could not be used to distinguish between benign and malignant tumours.

Antigens, Neoplasm↗

Serous ovarian cyst fluids contain high levels of endometrial placental protein 14.

This paper reports the detection and characterization of endometrial placental protein 14 (PP14) in human ovarian cyst fluids. PP14 from ovarian cyst fluid has the same molecular size as PP14 purified from human amniotic fluid. No clear difference was found in the PP14 concentrations between benign, borderline and malignant cyst fluids, but serous ovarian cyst fluids had significantly higher PP14 concentrations (median 253.3 micrograms/l) than mucinous cyst fluids (median 17.5 micrograms/l).

Adult↗