Use of two epithelium-specific monoclonal antibodies for diagnosis of malignancy in serous effusions

Two monoclonal antibodies, HMFG2 and AUA1, raised against epithelial-cell determinants were used to detect carcinoma cells in smears of serous effusions. Both antibodies react strongly with malignant epithelial cells but not with normal mesothelial or endothelial cells. A third antibody, 11-4.1, which does not react with any human tissue, was used as a negative control. An immunoperoxidase-staining technique was applied to smears of cells from serous effusions. The immunohistochemical diagnosis was in agreement with the cytological diagnosis. In cases with equivocal cytology in which the diagnosis became clear in later samples, the immunohistochemical diagnosis gave the correct result. With this combination of tumour-associated monoclonal antibodies a confident diagnosis of malignancy in serous effusions can be made.     

Lymphocyte and lymphocyte subsets in pleural fluid--comparison of malignant and non-malignant disorders

The role of lymphocytes in host defence in neoplastic disorders is known. Accumulation of lymphocytes in pleural cavity frequently occurs in different diseases. The aim of the study was to evaluate: 1) the frequency of lymphocyte predominance in different malignant and non-malignant pleural effusions; 2) lymphocyte phenotype and the ratio between helper (CD4+) and cytotoxic/suppressor (CD8+) lymphocytes in malignant and non-malignant effusions. Patients with mesothelioma, lung cancer, lymphoma and metastatic neoplasms were analysed. Analysis was performed on fluids with or without malignant cells. Non-malignant fluids were obtained from patients with: congestive heart failure, liver cirrhosis, pneumonia and tuberculosis. Lymphocytes were the predominant cell type in neoplastic effusions. For further analysis effusions with more than 10% of lymphocytes were included: 12 malignant and 9 non-malignant. For lymphocyte subpopulations analysis, the monoclonal antibodies anti-CD4 and anti-CD8 and APAAP method was used. We observed lower percentage of CD4+ lymphocytes (47%) and higher percentage of CD8+ (39%) lymphocytes in malignant when compared to non-malignant fluids (58% vs 31% respectively). The CD4+/CD8+ ratio was significantly lower in pleural fluid in cases with neoplastic disease when compared to benign cause of pleural involvement (1.03 vs 1.85). Our observations suggest the potential role of lymphocytes, especially CD8+ cells in local response in malignancy in pleural disease.     

Thoracoscopy with pleural brushing. A new diagnostic method for pleural diseases

Pleural brushing can be performed under thoracoscopic examination. The combined use of all three methods of diagnosis (macroscopy, biopsy, cytology) achieved optimal diagnostic results. From September 1980 to October 1981 we have performed 150 thoracoscopies for pleural effusions, while the results of conventional pleural cytology and biopsy were negative. In 108 cases pleural brushing and biopsy were both performed. The diagnosis was in 37 cases non malignant disease states associated with effusions and in 71 cases tumoural effusions. Among the 37 cases of non malignant diseases states associated with effusions were 6 mechanical effusions, 27 inflammatory processes, 4 infectious processes. Among the 71 cases of tumoural effusions were 3 benign pleural lipomas, 50 metastatic carcinomas, 18 carcinomatous mesotheliomas. We studied the diagnostic accuracy of pleural brushing: in non malignant diseases pleural brushing show the non tumoural features of the process, in metastatic tumours biopsy was positive in 80% of the cases; pleural brushing in 78% of cases; taken together they allowed the diagnosis in 86% of the cases, in carcinomatous mesotheliomas biopsy was positive in 82.3%, pleural brushing in 78%; taken together they allowed the diagnosis in 89% of the cases. Pleural brushing allows a rapid cytological diagnosis, enhances the histological results and may be used to get cellular material in areas dangerous to biopsy.     

Differential expression of jackfruit-lectin-specific glycoconjugates in metastatic adenocarcinoma and reactive mesothelial cells—a diagnostic aid in effusion cytology

Distinguishing reactive mesothelial cells from adenocarcinoma cells in serous effusions on the basis of morphological criteria alone is often difficult. Interest has therefore been focused on identifying reliable methods to supplement the conventional cytological techniques. Plant lectins have been reported as diagnostic markers for malignant cells. We studied 51 aspirated samples of benign and malignant effusions using horseradish-peroxidase-conjugated jackfruit lectin. No significant difference was observed between the cells of pleural and peritoneal fluids. The reactively proliferated mesothelial cells of benign effusions showed a predominence of mild staining while moderate and intense staining was predominant in malignant effusions. Intense and irregular lectin binding was observed in macrophages irrespective of the cause of effusion. The lectin staining method therefore appears to have some clinical significance as an additional diagnostic aid for use in effusion cytology.     

DNA ploidy, S-phase, and Ki-67 antigen expression in the evaluation of cell content of pleural effusions

Cells from pleural effusions (28 malignant and 14 nonmalignant with reactive mesothelial cells) were examined in parallel by means of conventional cytology and multiparametric flow cytometry. The latter included the evaluation of DNA ploidy, the calculation of DNA index (DI), the determination of S phase fraction (SPF), and cell proliferation associated with Ki-67 antigen expression. Propidium iodide was used for the DNA staining, and fluorescein-conjugated monoclonal mouse antibodies were applied to the human Ki-67 antigen staining. The specimens were analyzed by the Becton Dickinson (BD) FACScan apparatus. 10⁴ events were collected, and thereafter the obtained data were analyzed by the software Lysis II and CellFit (BD) for DNA and Ki-67 data analysis, respectively. Out of the 28 cases examined, 18 (64%) of the malignant effusions were aneuploid. All of the benign effusions were typically diploid. The average SPF of benign, malignant diploid, and malignant aneuploid cases was 6, 6, and 30 respectively. The comparison between SPF and DI in malignant cases showed a significant correlation (p < 0.001). The average of Ki-67-positive cells that were benign, malignant diploid, and malignant aneuploid were 11, 19, and 35, respectively. There was a significant correlation between Ki-67 expression, SPF (p < 0.05), and the percent of the aneuploid cell population (p = 0.01). The sensitivity of conventional cytology, the determination of DNA ploidy and of Ki-67 expression, was 80, 64, and 92%, respectively; specificity was 100% for cytology and DNA ploidy and 46% for Ki-67 expression. These data show that Ki-67 antigen expression is a potentially useful adjunct to cytometric DNA content analysis, determination of SPF, and conventional cytology in the diagnosis of malignant pleural effusions. Offprint requests to: J. Zeromski     

Tumormarker im Perikarderguss bei malignen und nichtmalignen Perikarderg��ssen

Background

The differential diagnosis of pericardial effusion is often challenging because different etiologies can be discussed. Of particular therapeutic and prognostic importance is the definitive differentiation of malignant pericardial effusion from benign effusions. The definitive diagnosis of malignant pericardial effusion is established by a positive cytological examination of the pericardial fluid. However, pericardial fluid cytology, although specific has variable sensitivity. Tumor markers are often investigated after pericardiocentesis but their utility as an aid for the diagnosis of malignant pericardial effusion is not well established. The aim of this study was to measure the concentrations of the tumor markers CEA, CA?19-9, CA?72-4, SCC and NSE in malignant and non-malignant pericardial effusions and to assess their diagnostic utility in differentiating malignant from benign pericardial effusion.

Methods

We investigated the pericardial fluid of 29?patients with proven malignant pericardial effusion and 25?patients with non-malignant pericardial effusion. The etiology of the pericardial effusion was defined by pericardial cytology, epicardial histology and PCR for cardiotropic viruses from pericardial and epicardial tissue acquired by pericardioscopy. The group with non-malignant pericardial effusion comprised 15?patients with autoreactive effusion and 10?patients with viral pericardial effusion. We analyzed the following tumor markers in the pericardial fluid: carcinoembryonic antigen (CEA), carbohydrate antigen (CA)?19-9, carbohydrate antigen (CA)?72-4, squamous cell carcinoma (SCC) antigen and neuron-specific enolase (NSE).

Results

Of the tumor markers tested the mean concentrations of the CEA, CA?72-4 and CA?19-9 were significantly higher in malignant pericardial effusions than in non-malignant effusions (CEA 450.66 ±1620.58???g/l vs. 0.72 ±1.49???g/l, p<0.001; CA?19-9 1331.31 ±3420.87?kU/l vs. 58.85 ±17.53?kU/l, p=0.04; CA?72-4 707.90 ±2397.55?kU/l vs. 0.48 ±2.40?kU/l, p<0.001). ROC curve analysis showed that pericardial fluid CA?72-4 yielded an area under the curve (AUC) of 0.85 (95% confidence interval 0.74?C0.95), followed by CEA with 0.80 (95% confidence interval 0.68?C0.92). Pericardial fluid CA?72-4 levels >1.0?kU/l had 72% sensitivity (95% confidence interval 53%?C87%) and 96% specificity (95% confidence interval 80%?C99.9%) and CA?72-4 levels >2.5?kU/l had 69% sensitivity (95% confidence interval 49%?C85%) and 96% specificity (95% confidence interval 80%?C99.9%) in differentiating malignant pericardial effusions from effusions due to benign conditions.

Conclusion

Malignant pericardial effusions are associated with significantly higher pericardial concentrations of the tumor markers CEA, CA?72-4 and CA?19-9. Of the tested tumor markers, measurement of CA?72-4 levels in pericardial fluid offered the best diagnostic accuracy. Based on our data evaluation of every patient with unexplained pericardial effusion and negative pericardial fluid cytology should include the measurement of pericardial fluid CA?72-4 levels. Under these circumstances the elevation of pericardial fluid CA?72-4 levels should include malignancy as a probable diagnosis.     

Subxiphoid pericardiotomy in the diagnosis and management of large pericardial effusions associated with malignancy.

To determine the safety, diagnostic value, and clinical outcome of patients with malignancy undergoing subxiphoid pericardiotomy for large pericardial effusions, we prospectively studied 25 consecutive patients with malignancy and new, large pericardial effusions diagnosed by echocardiography. Twenty-two of the 25 operations were done under local anesthesia, and no patient died at surgery. Pericardial fluid cytology revealed malignant cells in 11 patients (44 percent), while tumor was seen in only five (45 percent) of these 11 patients on pathologic examination. The remaining 14 patients showed no evidence of pericardial invasion with tumor. Evidence of intrathoracic disease by CT or MRI scanning, tamponade, a sanguineous pericardial fluid character, and an elevated serum and pericardial fluid lactate dehydrogenase level all were suggestive of malignant invasion of the pericardium. All 25 patients were followed at least 12 months postoperatively. Effusions recurred in three patients (12 percent), and one patient required reoperation. Overall mortality was 72 percent with a 91 percent (10 of 11) mortality for those with malignant effusions and a 57 percent (8 of 14) mortality for those with nonmalignant effusions. Diagnostically, subxiphoid pericardiotomy has little advantage over examination of pericardial fluid alone in this group of patients. Therapeutically, however, it is a low morbidity procedure which is safe and effective in treating patients with malignancy and large pericardial effusions.     

Investigation of pleural effusion: comparison between fibreoptic thoracoscopy, needle biopsy and cytology

Twenty-eight patients with exudative pleural effusion have been investigated by fibreoptic thoracoscopy, Abrams needle biopsy and pleural fluid cytology. Sixteen patients had previously had negative pleural biopsies and cytology. Twenty effusions were malignant (16 mesothelioma, four metastatic carcinoma), seven were due to nonspecific inflammation and in one case no abnormality was found. The diagnostic yield for all three techniques combined was 85%, for thoracoscopy alone 65%, Abrams biopsy 60% and cytology 45%. In 12 patients presenting without previous investigation all eight malignant effusions were correctly diagnosed by at least one of the techniques with individual sensitivities of 75% for thoracoscopy, 63% for Abrams and 38% for cytology. Of the 16 patients who had previously had negative investigations 12 had malignant effusions, nine (75%) of which were diagnosed by a combination of the techniques. In this group, the individual sensitivities were 58% for both thoracoscopy and Abrams and 50% for cytology. A correct diagnosis of malignancy was made by a combination of needle biopsy and cytology in 75% of patients with previous investigations and 88% of those without. Fibreoptic thoracoscopy added only two diagnoses of malignancy to those obtained by Abrams and cytology. The limitations of the technique render it unsuitable for routine investigation of pleural effusions.     

A comparative study of pleurodesis using talc slurry and bleomycin in the management of malignant pleural effusions

Differing success rates of various pleurodesis agents have been reported in the management of malignant pleural effusions. A randomized clinical trial was conducted to compare the efficacy of two commonly used agents, talc and bleomycin, for the pleurodesis of malignant pleural effusions. Methodology : Inclusion in the study required proof of a malignant pleural effusion by fluid cytology or pleural biopsy. Exclusion criteria included trapped lung, loculated effusions, recurrent effusions and life expectancy < 1 month. Five grams of talc or 1 unit per kilogram bodyweight of bleomycin mixed in 150 mL of normal saline was administered via tube thoracostomy after complete drainage of the pleural effusion in each patient. Treatment success was defined as the absence of recurrent pleural effusion on the chest radiograph 1 month after pleurodesis. Results : Treatment success was achieved in 16 out of 18 patients (89%) in the talc slurry group versus 14 out of 20 patients (70%) in the bleomycin group (P = 0.168). Fever and pain were the only side‐effects of pleurodesis in both groups. Conclusion : These results indicate that talc slurry is as effective as bleomycin in preventing early recurrence of malignant pleural effusions. Pleurodesis with talc instead of bleomycin can result in significant cost savings.     

E-cadherin and calretinin as immunocytochemical markers to differentiate malignant from benign serous effusions

AIM: To investigate the expressions of E-cadherin and calretinin in exfoliated cells of serous effusions and evaluate their values in distinguishing malignant effusions from benign ones. METHODS: Fresh serous effusion specimens were centrifuged and exfoliated cells were collected. Cells were then processed with a standardized procedure, including paraformaldehyde fixation, BSA-PBS solution washing and smears preparation. E-cadherin and calretinin were detected by immunocytochemistry (ICC). RESULTS: In the exfoliated cells of serous effusions, most of carcinoma cells only expressed E-cadherin, and most of mesothelial cells only expressed calretinin, and benign cells (lymphocytes and granulocytes) did not express either of them. For E-cadherin, 85.7% (30/35) of malignant effusions and 8.1% (3/37) of benign fluids were ICC-positive (P<0.001). The sensitivity of E-cadherin ICC in the diagnosis of malignant effusions was 85.7%, specificity 91.9%, and diagnostic rate 88.9%. For calretinin, 94.6% (35/37) of benign effusions and 11.4% (4/35) of malignant effusions were ICC-positive (P<0.001). The sensitivity of calretinin ICC in the diagnosis of benign effusions was 94.6%, specificity 88.6%, and diagnostic rate 91.7%. For diagnosis of benign and malignant effusions by combining E-cadherin ICC and calretinin ICC, the specificities were up to 100% and 97.1%, respectively. CONCLUSION: E-cadherin ICC and calretinin ICC are sensitive and specific in differential diagnosis of benign and malignant serous effusion specimens and specificities are evidently improved when both markers are combined.     

Neoplastic pericarditis--the role of different diagnostic procedures

The aim of the study was to assess the role of different diagnostic procedures in the recognition of malignant pericarditis. Consecutive medical records of the patients with pericardial effusion treated with pericardiocentesis or pericardioscopy in the period of 1982-2002 were analyzed retrospectively. Criteria of neoplastic pericarditis were: positive result of pericardial fluid cytology and/or neoplastic infiltration found in pericardial biopsy specimen. Criteria of non-neoplastic pericarditis were: negative result of pericardial fluid cytology and pericardial biopsy specimen, no neoplastic disease diagnosed at presentation and during 3-years of follow up. Malignant pericarditis was diagnosed in 47 patients (pts), nonmalignant in 51. Echocardiographic signs of cardiac tamponade were found in 80% of pts with neoplastic pericarditis and 40% of pts with non-malignant disease (p = 0.0001). Chest CT scan revealed the presence of enlarged mediastinal lymph nodes in 94% of pts with malignant pericarditis and only 11% of pts with non-malignant disease (p = 0.00001). Pericardial thickness on CT scan exceeded 8 mm in 75% of the pts with malignant pericarditis and 8% of pts with nonmalignant disease (p = 0.0003). Pericardial fluid (pf) CEA concentration was significantly higher in the patients with neoplastic pericarditis than in the pts with non-malignant process. CEA > 5 ng/ml and Cyfra 21-1>50 ng/ml were found in 43% of the pts with malignant pericarditis and none of the pts with benign pericarditis. Thus we recommend chest CT scan and pericardial fluid tumor markers (CEA and Cyfra 21-1) assessment as the procedures helpful in the recognition of malignant pericarditis.     

Soluble HLA class I molecules in malignant pleural and peritoneal effusions and its possible role on NK and LAK cytotoxicity

PURPOSE: To examine the amount of sHLA-I in malignant pleural and peritoneal effusions and its possible role in natural immune defense. METHODS: Three groups of patients (75 patients with malignancy, 21 with infection, and 27 with other diseases) were studied for sHLA-I value using an ELISA method. Cytolytic activity of freshly isolated pleural and peritoneal effusion-associated lymphoid (EAL) cells from 14 of cases with malignancy were examined and compared to that of ten non-cancerous patients. EAL cells were co-cultured with the autologous cell-free effusions immediately after collection and 3 days after incubation with IL-2. RESULTS: The mean value of sHLA-I in effusions was 1.01+/-1.36 micro g/ml, 0.97+/-1.20 micro g/ml, and 0.49+/-0.45 micro g/ml, respectively. Despite higher mean sHLA-I levels in malignant and infected patients, no significant difference between these groups was observed ( P >0.05). Generally, the amount of sHLA-I in peritoneal effusions was higher than that for pleural effusions, but the difference was not significant. There were also no statistical differences in the sHLA-I levels between sub-groups of patients with malignancy. EAL cells' killing activity in malignant and infected effusions was 68.15+/-11.73 and 78.28+/-14.41, respectively ( P=0.08). No correlation between sHLA-I level and NK activity of EAL cells from the patients was found. Almost all malignant cases after exposure to cell-free effusions displayed an increase in NK activity (from 68.66+/-11.13 to 74.2+/-12.39, P=0.042) and a decrease in LAK activity (74.5+/-18.30 vs 67.72+/-16.46, P=0.040). Whereas, the same experiment performed for non-malignant effusions showed a decrease in both NK activity and LAK activity. Changes in NK and LAK activity were not correlated with the amount of sHLA-I in the effusions. CONCLUSION: The presence of sHLA-I, particularly in malignant effusions, suggests a role for these molecules in tumor immunity in the peritoneal or plural environment; however, at least with these group of patients, sHLA-I appears not to be a unique determining factor on EAL cells' killing activity.     

Th1 and th2 cytokine profiles in malignant pleural effusion

Background: The alteration of Th1 and Th2 cytokine levels is the subject of controversy in pleural effusions caused by malignancy, a situation that favors a Th2 immune response. Objective: To examine the different levels of IL-4 and IL-10 (Th2 cytokines), and IL-2 and interferon-γ (IFN-γ) (Th1 cytokines) in malignant and non-malignant pleural effusions. Method: The cytokine levels in pleural fluid of 62 patients with malignant pleural effusion (44 with lung cancer and 18 with extrathoracic tumors), 8 with tuberculous and 8 with congestive heart failure pleural effusion were analyzed using enzyme-linked immunosorbent assays. Results: IL-2 was below the detectable concentration of the assay. A significant decrease in IFN-γ level was observed in malignant but not in congestive heart failure cases compared to tuberculous cases. IL-10 levels were higher in malignant and tuberculous pleural effusions than in congestive heart failure pleural effusions, however, this difference did not reach the significant level. IL-4 levels were also increased non-significantly in lung cancer pleural effusions compared to the other groups. Conclusion: Our results show a wide variation in IL-4, IL-10, and IFN-γ levels in malignant pleural effusions, a pattern which was not convincing enough to differentiate the cause of effusion.     

Immunocytochemistry and ELISA quantitation of mucin for diagnosis of malignant pleural effusions.

One hundred and thirty-five pleural effusions with definite etiology were analyzed by mucin-specific monoclonal antibody (17Q2)-derived enzyme-linked immunosorbent assay (ELISA). Twenty-four effusions were transudate, 45 were nonmalignant exudate, and 66 were malignant. Among the 66 malignant effusions, 52 were adenocarcinoma, and 14 were malignancies other than adenocarcinoma. Purified mucous glycoproteins from sputa of normal subjects were used as ELISA standard. Our results showed that the mean mucin concentration in malignant pleural effusions were significantly higher than that of benign exudates (8.41 +/- 13.48 ng/ml versus 1.09 +/- 0.82 ng/ml, p < 0.01). Mucin concentration in malignant pleural effusions caused by adenocarcinoma was also significantly higher than in non-adenocarcinoma effusions (9.96 +/- 14.81 ng/ml versus 2.66 +/- 1.74 ng/ml, p < 0.01). With the use of mean +/- 2 SD of mucin concentration in benign exudates as a cut-off value (2.73 ng/ml), the sensitivity of this assay for diagnosis of malignant effusions was 66.7%, specificity was 97.1%, and accuracy was 82.2%. High levels of mucin concentration were more specifically associated with adenocarcinoma. When the mucin concentration in pleural effusions was greater than 5 ng/ml, 93.1% (27/29) of patients were adenocarcinoma. If the mucin concentration was greater than 10 ng/ml, 100% (14/14) of patients were adenocarcinoma. Immunofluorescent staining by mucin-specific monoclonal antibody 17Q2 were also carried out in diastase-treated cell preparations obtained from 22 patients with malignant pleural effusions and 16 benign exudates. Nine of 14 adenocarcinomas (64.2%) were reactive with monoclonal antibody 17Q2, while none of the benign exudates, squamous cell carcinomas, and mesotheliomas were stained.(ABSTRACT TRUNCATED AT 250 WORDS)     

The usefulness of 99mTc-SestaMIBI scan in the diagnostic evaluation of thyroid nodules with oncocytic cytology

OBJECTIVE: To assess the relevance of (99m)Tc-SestaMIBI (MIBI) scan in the diagnostic evaluation of thyroid nodules with oncocytic cytology. SUBJECTS AND METHODS: Twenty-four patients with a single (or prevalent) 'cold' solid nodule with Hurthle cells (HC) at fine needle aspiration cytology (FNAC) were studied. Cytological diagnosis of oncocytic metaplasia (OM) or HC tumor (HCT) was made when HC on the smear were comprised 10-75%, or >75%. Nodules concentrating MIBI at early and late (2 h after washout) stages were considered MIBI-positive. In all cases histological findings were obtained after total thyroidectomy. RESULTS: FNAC was malignant or suspect for malignancy in 16 cases (six HCT and 10 OM) and not suspect in eight (two HCT and six OM). Histological examination revealed 14 malignant tumors (11 HCT and three OM), and 10 benign thyroid lesions (three HCT and seven OM). Sensitivity of FNAC for malignancy was 92.8% and specificity was 70.0%; HCT were identified by FNAC in only 35.7% and OM in 70.0% of cases. No significant difference in MIBI positivity was found between malignant and benign thyroid nodules. The highest percentage of MIBI positivity was found in HCT (78.5%), but MIBI-positive nodules were also observed in thyroid lesions with HC metaplasia (40.0%). CONCLUSIONS: MIBI scintiscan has no value in differentiating malignant from benign HC thyroid neoplasias. Most HCT are MIBI-positive, but this scan is not sufficiently specific to differentiate true HC neoplasias from other thyroid lesions showing HC at FNAC, although an MIBI-negative scan strongly supports the absence of true HCT.     

Diagnostic value of biochemical biomarkers in malignant and non-malignant pericardial effusion

The aim of this study was to examine the biochemical composition of pericardial effusions of different etiology and to evaluate the diagnostic utility of biochemical parameters and tumor markers to discriminate malignant from benign effusion. Pericardial and serum levels of biochemical parameters and tumor markers were compared in 105 patients who underwent pericardiocentesis and pericardioscopy with targeted epicardial biopsy. Etiologic diagnosis was based on pericardial fluid and epicardial biopsy analysis by cytology, histology, immunohistochemistry, microbiology and polymerase chain reaction. The total of 105 patients comprised 29 patients with malignant and 76 patients with non-malignant pericardial effusions (40 autoreactive, 28 viral, 5 postcardiotomy syndromes and 3 associated with systemic diseases). Malignant pericardial effusions had significantly higher pericardial fluid levels of the tumor markers CEA, CA 19-9, CA 72-4, SCC and NSE (p < 0.001, p = 0.002, p < 0.001, p = 0.004 and p < 0.001, respectively) as well as higher pericardial fluid hemoglobin (p < 0.001), pericardial fluid white blood cells (p = 0.003), pericardial fluid LDH (p < 0.001) and ratio of pericardial to serum LDH levels compared to benign effusions. None of the biochemical or cell-count parameters tested proved to be accurate enough for distinguishing malignant from benign effusions. However, measurement of pericardial CA 72-4 levels offered a high diagnostic accuracy for malignancy, particularly in bloody pericardial effusions. None of the biochemical parameters tested was useful for the discrimination of malignant from benign effusions. However, measurement of pericardial CA 72-4 levels in bloody pericardial effusions yielded a high diagnostic accuracy and thus offers the potential as a diagnostic tool to distinguish between malignant and benign effusions.     

Quantitative DNA and morphometric analysis of gastroscopic brush smears by TV image analysis

OBJECTIVES: To determine quantitative nuclear morpho-and densitometric classifiers and classification techniques for analysis of gastric, Feulgen-stained brush smears. DESIGN: TV image analysis-based quantitative DNA and morphometric analysis of gastric brush smears in a prospective study. PATIENTS AND METHODS: Ninety-eight (11 normal, 77 gastritis (17 with intestinal metaplasia) and 10 adenocarcinoma) Feulgen-Schiff-stained gastric brush smears were analysed by TV image analysis. The classification of the smears was based on parallel histological examination. For standards, DNA content of lymphocyte cell cultures was determined by the image and by flow cytometry. From every nucleus, six morphometric (surface, layers, minimum diameter, maximum diameter, perimeter and form factor) and six densitometric (integrated optical density (IOD), average density, sigma density, minimum and maximum density and density range) parameters were simultaneously determined. The smear parameters (object cells CV, DNA index, 2c deviation index, 5c exceeding rate, G1 -S-G2 ratio) were analysed together with the mean and SD values of the nuclear parameters by discriminant analysis and back-propagation neural networks. RESULT: The normal smears were all diploid and their S + G2 ratio was 15.24+/-7.75% (mean +/- SD). The gastritis smears were all diploid with a proliferation fraction of 20.89+/-6.75%. The tumours were aneuploid in eight of the ten cases with 5c exceeding rate > 6.23%, the S + G2 fraction ratio was 34.72+/-10.12%. The mean nuclear surface area was 46+/-20, 58+/-20 and 74+/-22 microm2 in normal, gastritis and malignant groups, respectively. Significant differences (P<0.05) were found in nuclear surface, minimum and maximum diameter, and perimeter parameters. Using linear discriminant analysis, 100% of the non-malignant cases and 70% of the tumour cases were correctly classified. Using 30 non-malignant and five malignant cases as a training set, the neural networks classified 95% of the remaining cases correctly. The DNA index increased significantly (P<0.05) in Helicobacter pylori-positive cases compared to the negative ones. In gastritis with intestinal metaplasia, the proliferation ratio decreased significantly (P<0.05). CONCLUSIONS: The image analysis is a useful tool for quantitative gastric cytology. The combination of nuclear morphometric parameters and neural network classifiers with multivariate quantitative DNA analysis is suggested for gastric brush smear quantitative cytology analysis.     

Immunochemistry of otitis media with effusion.

For investigation of the nature and origin of middle ear effusions, immunochemical studies were performed on more than 400 patients diagnosed as having otitis media with effusion. Although results of cellulose acetate and disc electrophoretic analyses and quantitation of IgG, IgA, and IgM suggested that proteins found in the effusions were derived for the most part from the serum, quantitative analysis of secretory IgA revealed the existence of appreciable amounts of secretory IgA in both serous and mucoid effusions. The antigenicity and subunit structure of the secretory IgA isolated from middle ear effusions were identical or very similar to those of secretory IgA obtained from other external secretions. Radioactive single radial diffusion analysis of IgE showed that the mean concentrations of IgE in effusions and sera were within normal ranges. Findings of this study suggest that the middle ear maintains the local immunologic defense system, that the middle ear effusion is at least partially an external secretion, and that IgE in middle ear effusions obtained from old patients, rather than being a local product, may be derived from the serum.     

可弯曲电子内科胸腔镜在恶性胸腔积液诊断中的应用

目的探讨可弯曲电子内科胸腔镜在恶性胸腔积液诊断中的应用时机和指征。方法2005年7月至2007年7月,对首都医科大学附属北京朝阳医院应用尖端可弯曲电子内科胸腔镜(LTF-240型)检查并确诊的37例恶性胸腔积液患者临床资料进行回顾性分析,所有患者经胸腔积液细胞学、痰细胞学、支气管镜检查等仍不能确诊胸腔积液性质,临床上高度疑诊恶性胸腔积液者,行内科胸腔镜治疗。结果37例患者最终诊断:肺癌20例,其中肺鳞癌5例(其中1例经手术证实,而胸腔镜检查为阴性),肺腺癌12例,肺腺鳞癌1例,小细胞癌2例;胸膜转移癌14例,其中乳腺癌转移4例,卵巢癌转移1例,肾透明细胞癌并胸膜转移1例,恶性胸腺瘤转移1例,其他部位转移癌7例;恶性胸膜间皮瘤2例;非霍奇金淋巴瘤1例。主要并发症为术后伤口疼痛(21例),对症治疗可缓解,无肺水肿、感染、出血等并发症。结论可弯曲电子内科胸腔镜检查是一项安全、有效、易操作的检查方法,对有肿瘤病史、大量胸腔积液、胸部CT提示肿块影或胸膜病变者可早期积极进行内科胸腔镜检查。     

Cytogenetic analysis of metastatic effusions from breast tumors

Chromosome analysis was performed on direct and in vitro cultures of 30 effusions from breast carcinoma. Although in 14 samples normal diploid stem-lines were found, chromosome abnormalities were present in stem- or side-lines of all cases. Recurrent numerical deviations were only verified as gains of Nos. 6 and 7. Rearrangements were seen involving almost all chromosome pairs (except No. 18 and gonosomes), however, Nos. 1, 3, 6 and 11 were those most frequently related to the genesis of markers. Double minutes (DMs) were found in seven samples, and there was a homogeneously staining region (HSR) in one.