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Intrahepatic biliary cystadenoma: role of cyst fluid analysis and surgical management in the laparoscopic era.

BACKGROUND: Recent interest in cyst fluid analysis (CFA) for carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA), and the introduction of laparoscopic surgery (LS) in the management of hepatic cysts have resulted in sporadic reports of elevated CA 19-9 and CEA levels in intrahepatic biliary cystadenoma (IBC) CFA, and the application of LS in the management of simple cysts. However, the role of CA 19-9 and CEA in the diagnosis of IBC and the role of LS in the management of IBC have not been previously defined. METHODS: We studied 34 patients with IBC at a single institution (8 years). The first 12 patients with IBC were managed with open surgical intervention. We subsequently developed a diagnostic and treatment algorithm for IBC that included, in the last 22 patients, prospective analysis of CFA for CA 19-9 and CEA, and LS for management RESULTS: All patients with IBC who underwent CFA had elevated CA 19-9 (range, 2247-1,757,510; N <33 U/mL) and mildly elevated CEA (range, 3.3-212,; N <3 ng/ml). In all 22 patients the cyst lining consisted of biliary epithelium +/- mesenchymal stroma (MS). In 1/22 patients (highest CA 19-9 level), the cyst epithelium did not contain either MS or intestinal metaplasia. In contrast, control patients (simple cysts, n=8) had normal CFA. In the previous 12 patients managed with laparotomy, 6/12 patients had biliary epithelium alone; the other 6 also contained MS with 1 patient exhibiting intestinal metaplasia and cystadenocarcinoma. CONCLUSIONS: We have proposed a management algorithm for IBC that incorporates CFA and laproscopic surgical management that allows for selective minimally invasive cyst wall sampling for patients with IBC.

Algorithms↗

Purification and properties of an esterase from human breast cyst fluid.

Levels of estradiol 17 beta-ester hydrolytic activity in the breast cyst fluid (BCF) from 25 different women with fibrocystic disease of the breast were found to vary over a wide range (0-2.4 nmol/min/mg protein for estradiol acetate). On the basis of electrophoretic mobility on agarose gels, the activity from different individuals appeared to be identical. The esterase activity from a single BCF sample was purified to near homogeneity by differential ammonium sulfate precipitation, ion-exchange, and hydrophobic interaction chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, after the final purification step, showed two bands with molecular weights of approximately 22,000 and 23,000, neither of which was immunoreactive with a rabbit antibody raised to a crude esterase-free BCF preparation. Esterase activity could be demonstrated after extraction and renaturation of the protein eluted from the Mr 22,000 band. Resolution of the gel, however, was not good enough to rule out the presence of esterase activity in the Mr 23,000 protein. High performance liquid chromatography gel exclusion chromatography indicated a molecular weight of 90,000-95,000 for the esterase activity in crude BCF and approximately 225,000 for the purified activity, suggesting the native protein to be a tetramer which aggregated during purification. Although the natural substrate of the BCF esterase is unknown, the enzyme is able to cleave a variety of esters including acetate, valerate, and stearate esters of estradiol and p-nitrophenyl hexanoate. It is completely inhibited by diisopropylflurophosphate and diethylnitrophenyl phosphate and partially inhibited by NaF and ebelactone. The substrate and inhibitor profile of the enzyme indicates that it is a "B"-type carboxylesterase and not a protease. A comparison of the properties of the BCF esterase with those of esterases from the formed elements of the blood or from plasma suggests that the BCF esterase is not of blood origin and is probably derived from the cyst itself. Physiologically inactive lipoidal estrogens have been shown to be present in many human body fluids and tissues and it is possible that these esters serve as storage forms of the active hormone in hormonally sensitive tissues where the free steroid could be regenerated by hydrolysis.

Anti-Bacterial Agents↗

Shunting procedures in the management of intracranial cerebrospinal fluid cysts in infancy and childhood.

Widely diverging opinions on the optimal therapy for intracranial cerebrospinal fluid cysts (CSF), mainly arachnoid cysts and the Dandy-Walker cysts, exist. Excision of the cyst walls in the treatment of the Dandy-Walker cyst has been replaced by shunting procedures, but the recommended method for primary treatment of arachnoid cysts in childhood is still cyst wall excision. Membrane excision is, however, often complicated by recurrence, subsequently requiring shunting-procedures. In a series of 19 cases primary shunting of intracranial CSF cysts proved to be a reliable method. In those cases where hydrocephalus (ventricular dilatation) is present at the time of the primary operation the ventricles should be shunted as well as the cyst. The catheter from the ventricle and that from the cyst should be connected to the same valve, otherwise an increased risk of intracranial herniation exists. The prognosis for infants and children suffering from intracranial CSF cysts is in general good; in 17 out of 19 cases mental development was normal and in 15 out of 19 motor development was normal. The risk of permanent motor damage seems to be particularly high when an arachnoid cyst is located on the quadrigeminal plate.

Arachnoid↗

Lactate dehydrogenase, isoenzyme patterns and cation levels in human breast gross cyst fluid.

In order to investigate the diagnostic and/or prognostic value of total activity and isoenzymatic patterns of lactate dehydrogenase, 24 human breast gross cystic fluids were studied. A comparison of total lactate dehydrogenase activity to the serum level revealed an increased activity in about 63% of the cases examined; moreover, a significant increase in the slow-moving lactate dehydrogenase 4 and 5 isoenzymes was observed in some cyst fluids. The levels of Na+ and K+ concentrations were also analyzed and two classes of cysts were identified: one presenting Na+ and K+ levels similar to those found in extracellular compartment; the other with high K+ and low Na+ levels, characteristic of an intracellular fluid. This latter pattern could indicate an active metabolism of the epithelial cells lining the cysts. This breast cyst fluid also showed increased levels of lactate dehydrogenase 4 and 5 isoenzymes. The correlation between an increased activity of lactate dehydrogenase 4 and 5 isoenzymes and high K+ and low Na+ levels could be the expression of a high biosynthetic activity and of an anaerobic metabolism in some cysts, suggesting the evolution of the breast gross cyst lesion to malignancy. The importance of these observations is discussed.

Body Fluids↗

Inhibition of oestrone sulphatase activity in the MDA-MB-231 breast cancer cell line by breast cyst fluid from Malaysian women.

Oestrone sulphate is a major source of active oestrogens in the breast. It is converted to oestrone by oestrone sulphatase. Breast cyst fluid (BCF) is a rich source of sex hormones and growth factors. BCF obtained from British women has been shown to inhibit oestrone sulphatase activity in the MCF-7 oestrogen-receptor-positive breast cancer cell line. The aim of the present study was to assess whether BCF obtained from Malaysian women inhibited oestrone sulphatase activity in the MCF-7 and MDA-MB-231 breast cancer cell lines. The cell lines were grown in supplemented Dulbecco's Modified Eagle Medium for 3 days, following which a 3-day incubation with sterilised BCF was carried out. At the end of the treatment period the cell monolayers were assayed for oestrone sulphatase activity and the number of cell nuclei counted on a Coulter Counter. BCF was also fractionated on a Bio-Sil SEC 125-5 column by HPLC and the effects of the fractions collected on oestrone sulphatase activity in the MDA-MB-231 cell line were assessed. All 18 samples of BCF tested inhibited cell growth in the MDA-MB-231 cell line while 8 out of 10 samples inhibited MCF-7 cell growth; 15 out of 18 BCF samples inhibited oestrone sulphatase activity in the MDA-MB-231 cell line whereas 5 out of 10 samples stimulated oestrone sulphatase activity in the MCF-7 cell line. HPLC fractions corresponding to molecular weights of > 158 kDa and 28 kDa were found to inhibit oestrone sulphatase activity in the MDA-MB-231 cell line. Further work is required to fully characterise these substances as they may have roles to play in the prevention of breast cancer.

Breast Neoplasms↗

Effect of breast cyst fluid on oestrogen 17-oxidoreductase activity in MCF-7 breast cancer cells.

Breast cyst fluid (BCF) was found to stimulate oestrogen 17-oxidoreductase activity in the reductive direction, i.e., conversion of oestrone (E1) to oestradiol (E2), in MCF-7 breast cancer cells. Dialysis of BCF revealed that this property of BCF was present in both dialysed BCF and dialysate, implying that both high and low mol. wt. substances were responsible for stimulating E1 to E2 conversion. Gel filtration of dialysed BCF revealed that the high mol. wt. substances responsible for the stimulation of E1 to E2 conversion had mol. wts. of approximately 11 kD and 68 kD. This property of BCF would serve to increase the concentration of E2, a steroid which may play a role in mammary carcinogenesis.

Body Fluids↗

Modulation of oestrone sulphate formation and hydrolysis in breast cancer cells by breast cyst fluid from British and Hungarian women.

Women with gross cystic breast disease may have an increased risk of breast cancer. In this study the ability of breast cyst fluid (BCF), obtained from British or Hungarian women, to modulate oestrone sulphate (E1S) formation or hydrolysis, has been examined. For this, oestrogen receptor-positive (ER+) MCF-7 or MDA-MB-231 (ER-) breast cancer cells were employed. The formation and hydrolysis of E1S was measured using radiometric techniques. BCF from British and Hungarian women mainly inhibited E1S hydrolysis in MCF-7 cells while stimulating hydrolysis in MDA-MB-231 cells. The extent of inhibition or stimulation of E1S hydrolysis in these cells was related to the Na+/K+ ratio of the BCF. There was a significant inverse relationship between the extent to which BCF samples inhibited hydrolysis in MCF-7 cells and stimulated it in MDA-MB-231 cells. BCF stimulated E1S formation in MCF-7 cells while inhibiting formation in MDA-MB-231 cells. No difference in the ability of BCF from British or Hungarian women to inhibit or stimulate E1S hydrolysis was detected in ER+ or ER- breast cancer cells. In contrast, BCF from British women stimulated E1S formation in ER+ cells (median 82%) to a significantly greater extent (P < 0.01) than BCF from Hungarian women (median 33%). The role that E1S has in breast cancer development remains unclear. The greater stimulation of E1S formation by BCF from British women, who have a higher risk of breast cancer than Hungarian women, suggests that it may act as a storage form of oestrogen within cells that can be activated by oestrone sulphatase.

Breast Neoplasms↗

[Surgical treatment of suprasellar cerebrospinal fluid cysts].

The authors discuss 18 child patients with suprasellar cysts containing cerebrospinal fluid; 16 of them were operated on. The following types of interventions were performed: ventriculocisternostomy, ventriculoatriostomy, excision of the cystic walls through a transventricular-transcortical, combined subfrontal and transcallosal, and only a subfrontal approaches; shunting operations--cystoatriostomy and cystoperitoneostomy. Excision of the walls of the cyst is preferable.

Adolescent↗

[Clinical picture and roentgenoradiological diagnosis of suprasellar cerebrospinal fluid cysts in children].

Suprasellar cysts containing cerebrospinal fluid are considered a rare pathological condition. Characteristic symptom complexes in children are discussed on the basis of 12 cases. It is assumed that signs of affection of the chiasma and optic nerves in slowly progressive hydrocephalus, diencephalic disorders, and hyperkinesis suggest the presence of a suprasellar cyst. The authors present data on the use of diagnostic methods of examination and give their opinion on the informative value of these methods: craniography, gamma-topography and radionuclide cisterno- and ventriculography, computerized tomography, and computerized-tomographic cisterno- and ventriculography.

Adolescent↗

Variability in cyst fluid carcinoembryonic antigen level, fluid viscosity, amylase content, and cytologic findings among multiple loculi of a pancreatic mucinous cystic neoplasm.

The procedure of percutaneous aspiration and analysis of cyst contents has been advocated to provide a preoperative diagnosis of pancreatic cystic lesions (pseudocysts and cystic tumors), but it is not known whether variation in the contents of separate loculi of a multilocular neoplasm might misrepresent the identity of the tumor. The authors measured the cyst fluid carcinoembryonic antigen (CEA) level, fluid viscosity, and amylase content and performed cytologic analysis on aspirates rates from ten different loculi of a single mucinous cystic neoplasm of the pancreas. The CEA levels were highly variable (median, 6,326 ng/mL; range, 962-64,670 ng/mL) but in all cases were diagnostic of a mucinous tumor. Fluid relative viscosity values were also variable (median, 2.4; range, 1.3-10+) but diagnostic in eight of nine aspirates. The amylase content in all of the loculi was low (< 91 U/L), and values were consistent with a cystic tumor. Cytologic analysis showed diagnostic mucin-secreting epithelial cells in nine of ten loculi. Although cytologic examination was nondiagnostic in one loculus, there were no false-positive results for malignancy. The combination of all four tests would not have resulted in misclassification of any of the tumors. The authors conclude that the characteristics of the contents of different loculi of pancreatic cystic neoplasms may be variable, but the use of a combination of tests still ensures accurate diagnosis.

Amylases↗

Correlation of concentrations of estriol-3-sulfate with those of potassium and sodium in human breast cyst fluid.

Estriol-3-sulfate (E3-3S) was assayed in 92 specimens of human breast cyst fluid (BCF) obtained by needle aspiration from women with fibrocystic disease. The concentrations of K+ and Na+ were determined in the same samples. The median concentration of E3-3S in the fluids from premenopausal women under 51 years of age (69 cases) was 4.4 ng/mL. Based on the K+ levels the samples were divided into two groups, above 50 mM (Type I) and below 50 mM (Type II). Correlations were made between the concentrations of the estrogen conjugate and the univalent ions. In the premenopausal women, Type I cysts were associated with above median E3-3S and Type II cysts with below median E3-3S (P less than 0.01). A K+/Na+ ratio of more than one was also related to elevated E3-3S (P less than 0.025). The BCF obtained from postmenopausal women and women older than 50 years tended to be low in E3-3S (median 1.64 ng/mL) and high in K+ but there were too few cases to permit statistical comparisons to be made. Since fibrocystic disease constitutes a risk factor for the development of breast cancer, it will be of interest to determine retrospectively whether any of the above subsets of BCF may be useful in identifying a patient at such risk.

Adult↗

Subunit composition and specificity of the major cyst fluid antigens of Echinococcus granulosus.

The subunit composition and specificity of the major Echinococcus granulosus cyst fluid antigens were determined by immunochemical analysis using murine monoclonal antibodies against Antigen 5 and Antigen B and human sera. Immune complexes cut out from immunoelectrophoresis gels and murine hybridomas were used as a source of specific anti-Antigen 5 and anti-Antigen B antibodies. Immunoprecipitation and Western blot analyses in sodium dodecyl sulphate-polyacrylamide gels using these reagents identified Antigen 5 to be a heterodimer composed of 24-kDa and 38-kDa subunits linked by disulphide bonding. Antigen B comprised a regularly spaced group of molecules with the smallest subunit estimated to be 8 kDa and the other components each differing in size by approximately 8 kDa, i.e., 16 kDa, 24 kDa, 32 kDa etc.; all possibly derived from the 8-kDa monomer. The relative abundance of the Antigen B subunits decreased asymptotically with increasing molecular weight. Neither the Antigen 5 nor the Antigen B subunit was specific for E. granulosus. Both antigens generated readily detectable levels of specific antibody in the sera of patients with Echinococcus multilocularis, Echinococcus vogeli or E. granulosus infection. Relatively high levels of antibody to Antigen 5 were also detected in the sera of patients infected with Taenia solium. The presence of phosphorylcholine epitope(s) on Antigen 5 was confirmed.

Animals↗

Evaluation of an antigenic fraction of Taenia hydatigena metacestode cyst fluid for immunodiagnosis of bovine cysticercosis.

An antigenic fraction (ThFAS) isolated from Taenia hydatigena metacestode cyst fluid was used in an ELISA to detect antibodies to T saginata in experimentally and naturally infected cattle. In 10 calves given 1,000 to 100,000 T saginata eggs (20% to 60% viability), IgG and IgM antibodies were detected in all the calves by post-inoculation week 3. Immunoglobulin G antibody values remained increased until calves were slaughtered at post-inoculation weeks 13 to 26. Six naturally infected calves (determined by postmortem examination) were considered positive, using the ELISA. Shared antigens were demonstrated between ThFAS and T saginata and T crassiceps; there were no shared antigens between ThFAS and Haemonchus contortus or Fasciola hepatica. Specific lectin binding to ThFAS indicated the presence of glycoconjugates. Immunoblot analysis indicated that a low molecular weight polypeptide (10,000 Mr) bears the immunodiagnostic antigen.

Animals↗

Serum and Cyst Fluid Tumor Marker Levels in the Differential Diagnosis of Benign Ovarian Cysts

Serum and cystic fluid levels of CA 125, CA 19.9, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) were assayed in 74 consecutive women of median age 30 years (range 15 to 74 years) undergoing surgery for adnexal cysts of presumed benign nature. Median (range) serum levels of CA 125, CA 19.9, CEA and AFP were 46.5 IU/ml (4.3-406), 28.5 IU/ml (1-96.3), 1.4 ng/ml (0.5-3.5) and 2.4 ng/ml (1-9.9) in 44 endometriotic cysts; 22.5 (4.7-82), 4.9 (1-226),1.3 (0.7-4.8) and 4 (0.5-10.5) in 11 dermoid cysts, 14 (8.6-25.1), 3.2 (1-6), 1 (0.3-2.8) and 3.7 (1.9-6) in 9 mucinous cysts, and 6.9 (0.5-104), 18 (1-132), 0.8 (0.1-1.9) and 2.1(1-5.4) in 10 cases with mixed histotypes. Corresponding cystic fluid levels were 342,864 (1,418-3,404,682), 228,000 (117-2,500,000), 106 (0.5-2,908) and 1.3 (0.4-51) in endometriomas; 843,895 (10,842-1,676,948), 740,039 (77-1,280,000), 470 (61-880) and 2.5 (1-4) in dermoids; 3,485 (27.2-149,804), 9,007 (36.4-153,475), 1,631 (402-11,096) and 1 (0.5-2.5) in mucinous cysts, and 13,068 (5,300-43,767), 412 (1-142,700), 0.8 (0.4-5.3) and 2.3 (1-4) in the mixed histotype group. No significant between group differences were detected in serum marker levels. Patients in the mucinous cyst group had significantly lower CA 125 cystic fluid levels compared with women with endometriomas and dermoids (P<0.05). Fluid aspirate tumor marker measurements did not aid in the differential diagnosis of benign ovarian cysts, mainly due to the extremely wide scattering of values.

Journal Article↗

Melatonin and estrogen in breast cyst fluids.

Increased breast cancer risks have been reported among women with gross cystic breast disease (GCBD), although the mechanism for this increase remains unexplained. Relationships between GCBD characteristics, breast cancer risk factors, and the biochemical composition and growth properties of 142 breast cyst fluid (BCF) samples were studied among 93 women with GCBD. Concentrations of melatonin, estrogen (17-beta-estradiol), dehydroepiandrosterone-sulfate (DHEA-S), epidermal growth factor (EGF), transforming growth factor beta (TGF-B1 and TGF-B2), sodium (Na), and potassium (K) were quantified in BCF samples, and human breast cancer cells (MCF-7) were treated with BCF in vitro. Patients were grouped according to BCF Na:K ratios previously linked with increased breast cancer risks (Na:K </= 3, Type 1), and mean concentrations of BCF constituents were compared with low risk (Na:K > 3, Type 2) and mixed cyst groups. Women with larger and more frequently occurring cysts had higher BCF estrogen and DHEA-S, and lower TGF-B1 levels. Women with Type 1 cysts had elevated BCF melatonin, estrogen, DHEA-S, and EGF, and lower concentrations of TGF-B2 compared to women with Type 2 cysts. BCF generally inhibited cell growth relative to serum-treated controls, consistent with previous studies. Melatonin and estrogen in BCF independently predicted growth inhibition and stimulation, respectively. Biological monitoring of BCF may help identify women with GCBD at greatest risk for breast cancer development.

Adult↗

Isolation and characterization of blood group N antigen precursor glycoproteins with Thomsen-Friedenreich (T) activity, N antigen precursor glycoproteins and T-active glycoproteins from cyst fluids of malignant ovarian clear cell carcinoma.

1. Two perchloric acid-soluble glycoprotein fractions from cyst fluids of 2 patients with ovarian clear cell carcinoma in malignant were subjected to a systematic affinity chromatography using Vicia unijuga lectin-Cellulofine column and Arachis hypogaea lectin-Cellulofine column and separated into four glycoproteins, blood group N antigen precursor glycoprotein with Thomsen-Friedenreich (T) activity, N antigen precursor glycoprotein, T-active glycoprotein and serologically inactive glycoprotein, respectively. 2. These serologically active glycoproteins isolated in yields of 0.3-3.3% of PASFs, were proved to be mucin-type glycoproteins with Mw of 509,000-2,772,000 Da and contained 33.9-81.7% carbohydrates.

Acetylgalactosamine↗