Is there an advantage to be gained from adding digital image cytometry of brush cytology to a standard biopsy protocol in patients with Barrett's esophagus?

BACKGROUND AND STUDY AIMS: The current gold standard in Barrett's esophagus monitoring consists of four-quadrant biopsies every 1-2 cm in accordance with the Seattle protocol. Adding brush cytology processed by digital image cytometry (DICM) may further increase the detection of patients with Barrett's esophagus who are at risk of neoplasia. The aim of the present study was to assess the additional diagnostic value and accuracy of DICM when added to the standard histological analysis in a cross-sectional multicenter study of patients with Barrett's esophagus in Switzerland. METHODS: One hundred sixty-four patients with Barrett's esophagus underwent 239 endoscopies with biopsy and brush cytology. DICM was carried out on 239 cytology specimens. Measures of the test accuracy of DICM (relative risk, sensitivity, specificity, likelihood ratios) were obtained by dichotomizing the histopathology results (high-grade dysplasia or adenocarcinoma vs. all others) and DICM results (aneuploidy/intermediate pattern vs. diploidy). RESULTS: DICM revealed diploidy in 83% of 239 endoscopies, an intermediate pattern in 8.8%, and aneuploidy in 8.4%. An intermediate DICM result carried a relative risk (RR) of 12 and aneuploidy a RR of 27 for high-grade dysplasia/adenocarcinoma. Adding DICM to the standard biopsy protocol, a pathological cytometry result (aneuploid or intermediate) was found in 25 of 239 endoscopies (11%; 18 patients) with low-risk histology (no high-grade dysplasia or adenocarcinoma). During follow-up of 14 of these 18 patients, histological deterioration was seen in 3 (21%). CONCLUSION: DICM from brush cytology may add important information to a standard biopsy protocol by identifying a subgroup of BE-patients with high-risk cellular abnormalities.

Lugol chromoendoscopy combined with brush cytology in patients at risk for esophageal squamous cell carcinoma.

BACKGROUND AND STUDY AIMS: Patients with achalasia or malignancies of the head and neck are at increased risk for esophageal squamous cell carcinoma. The discussion of a screening and surveillance program is controversial. The aim of the present study was to determine the diagnostic potential of Lugol chromoendoscopy combined with brush cytology to diagnose esophageal squamous cell carcinoma and high-grade dysplasia. Secondly, the benefit of additional biomarkers was investigated. PATIENTS AND METHODS: A total of 61 patients (21 patients with achalasia and 40 patients with malignancies of the head and neck) were included. Chromoendoscopy with 1.2% Lugol iodine solution with targeted biopsies and brush cytology processed by digital image cytometry (DICM) and fluorescence in situ hybridization (FISH) from unstained lesions (USLs) and stained mucosa were performed. RESULTS: Six of the 61 patients had USLs ≥2 cm. Four patients had high-grade dysplasia (HGD) or carcinoma in situ (CIS). One patient with HGD and one patient with CIS were detected only after Lugol chromoendoscopy. The sensitivity and specificity for detected HGD or CIS in USLs ≥2 cm were 100% and 96.5%. No dysplasia was found in USLs <2 cm. DNA ploidy by DNA cytometry and p53 loss of heterozygosity (LOH) by fluorescence in situ hybridization showed no additional impact on diagnostic accuracy. CONCLUSIONS: Lugol chromoendoscopy enhances the detection rate of high-risk lesions with dysplasia or carcinoma in situ in large unstained lesions. Biomarkers such as aneuploidy and p53 LOH from brush cytology were not of additional benefit in this setting.

[Fine-needle aspiration cytology. Aspects of a minimally invasive diagnostic procedure]. / Die Feinnadelpunktion. Aspekte einer minimal-invasiven Diagnosemethode.

All practicable applications of fine-needle aspiration cytology (FNAC) for palpable tumors or non-palpable lesions guided with endoscopic and imaging procedures are presented. Multidisciplinary procedures and the technical and biological aspects of FNAC are presented. Indications and diagnostic challenges of FNAC on selected organs and neoplasms are discussed based on personal experience and the literature. Skilled and well-trained cytopathologists, the quality of the aspirate and the cytological preparation as well as supplementary immunocytochemical and molecular genetic analyses are mandatory for reliable diagnostic results. The indications and advantages of liquid-based techniques are discussed.

Diffusion of tritiated water and 22Na+ through non-degraded hardened cement pastes.

Diffusion experiments through hardened cement pastes (HCP) using tritiated water (HTO) and 22Na(+), considered to be conservative tracers, have been carried out in triplicates in a glove box under a controlled nitrogen atmosphere. Each experiment consisted of a through-diffusion test followed by an out-diffusion test. The experimental data were inversely modelled applying an automated Marquardt-Levenberg procedure. The analysis of the through-diffusion data allowed the extraction of values for the effective diffusion coefficients, D(e), and the rock capacity factor, alpha. Good agreement between measured and calculated tracer breakthrough curves was achieved using both a simple diffusion model without sorption and a diffusion/linear sorption model. The best-fit K(d)-values were found to be consistent with R(d)-values measured in previous batch-sorption experiments. The best-fit values from the through-diffusion tests were then used to predict the results of subsequent out-diffusion experiments. Good agreement between experimental data and predictions was achieved only for the case of linear sorption. Isotopic exchange can only partially account for both the amount of tracer taken up in the batch-sorption tests and the measured retardation in the diffusion experiments and, hence, additional mechanisms have to be invoked to explain the data.

[Experiences with the import of products of animal origin during the World Exhibition Expo 2000]. / Erfahrungen bei der Einfuhr von Erzeugnissen tierischer Herkunft während der EXPO 2000.

The importation of products of animal origin from states that don't belong either to the European Union nor to the signatory states of the Agreement on the European Economic Area is subject to European and national law. The examination of these products on import has to be carried out at the approved and published border control points at the external borders of the European Union (including border control points at airports). Although there wasn't any exception of these regulations during the World Exhibition EXPO 2000 sometimes it occurred that foods of animal origin passed a border control point and reached the EXPO site without veterinary import controls. Numbers of cases are mentioned and exemplary cases are described. Further steps by the responsible supervisory authority (Department of Trade and Veterinary Matters of the Federal State Capital of Hannover) to secure the consideration with legislation on prevention of epizootic disease are also explained.

Ni phases formed in cement and cement systems under highly alkaline conditions: an XAFS study.

X-ray absorption fine structure (XAFS) spectroscopy was applied to assess the solubility-limiting phase of Ni in cement and cement minerals. The study reveals the formation Ni and Al containing hydrotalcite-like layered double hydroxides (Ni-Al LDHs) when cement material (a complex mixture of CaO, SiO2, Al2O3, Fe2O3 and SO3) was treated with Ni in artificial cement pore water under highly alkaline conditions (pH = 13.3). This finding indicates that Ni-Al LDHs and not Ni-hydroxides determine the solubility of Ni in cement materials.

Colloids in the mortar backfill of a cementitious repository for radioactive waste.

Colloids are present in groundwater aquifers and water-permeable engineered barrier systems and may facilitate the migration of radionuclides. A highly permeable mortar is foreseen to be used as backfill for the engineered barrier of the Swiss repository for low- and intermediate-level waste. The backfill is considered to be a chemical environment with some potential for colloid generation and, due to its high porosity, for colloid mobility. Colloid concentration measurements were carried out using an in-situ liquid particle counting system. The in-house developed counting system with three commercially available sensors allowed the detection of single particles and colloids at low concentrations in the size range 50-5000 nm. The counting system was tested using suspensions prepared from certified size standards. The concentrations of colloids with size range 50-1000 nm were measured in cement pore water, which was collected from a column filled with a highly permeable backfill mortar. The chemical composition of the pore water corresponded to a Ca(OH)2-controlled cement system. Colloid concentrations in the backfill pore water were found to be typically lower than approximately 0.1 ppm. The specific (geometric) surface areas of the colloid populations were in the range 240 m2 g(-1) to 770 m2 g(-1). The low colloid inventories observed in this study can be explained by the high ionic strength and Ca concentrations of the cement pore water. These conditions are favourable for colloid-colloid and colloid-backfill interactions and unfavourable for colloid-enhanced nuclide transport.

[Ultrasound and cytology: ultrasound-controlled fine needle puncture]. / Ultraschall und Zytologie: Ultraschall-gezielte Feinnadelpunktion.

Ultrasound guided fine needle aspiration biopsy has shown to be a safe and cost-effective method for diagnostic assessment in complex and nonpalpable lesions. Experience in aspiration technique, smearing and fixation of the sampled probe are prerequisites for a good diagnostic yield.

Fourth updated ESACP consensus report on diagnostic DNA image cytometry.

A task force of experts in the field of diagnostic DNA image cytometry, invited by the ESACP, and further scientists or physicians revealing experience in that diagnostic procedure (names are given in Addendum A), agreed upon the following 4th updated Consensus Report on Standardised Diagnostic DNA Image Cytometry during the 7th International Congress of that society in Caen, 2001. This report is based on the three preceding ones [6,14,17]. It deals with the following items:- Critical review and update of the definitions given in the 1997 Consensus Update;- Review and detailed description of basic terms, principles and algorithms for diagnostic interpretation;- Recommendations concerning diagnostic or prognostic applications in specific fields of tumour pathology. This update is not aimed to substitute the 1997 consensus, but to make necessary addenda and give more detailed descriptions of those items not unequivocally to interpret by potential users of the methodology.

Maintenance of water and food quality in the stabilization forces area of operations: German surveillance laboratories and the problem of expired field rations.

The medical services of the German contingent of the Stabilization Forces in Bosnia maintain a high-standard-preventive health care system. Because knowledge about German food and water surveillance laboratories is not widespread, these and the methods used for sample examinations as well as their analytical capacities are introduced. From July to November 1998, we examined 168 food samples. Three percent of them were considered unsafe for consumption as a result of microbiological contamination. None was considered unsafe for chemical reasons. Consequently, only one case of suspected food-borne infection occurred. Similar results were found when we examined water quality. Generally, microbiological contamination was low. One sample of mineral water (0.5%) was considered unsafe for consumption for chemical reasons. These findings suggest a high-quality standard of food and water supply for the Stabilization Forces in Bosnia. The maintenance of this level is an important aim of the German preventive health care system.

Bone marrow necrosis in two patients with acute promyelocytic leukemia during treatment with all-trans retinoic acid.

All-trans retinoic acid has been used for the treatment of acute promyelocytic leukemia (APL) with encouraging results. However, it has recently been associated with a number of potentially serious complications including the retinoic acid syndrome. We describe two patients with APL who were begun on all-trans retinoic acid therapy (45 mg/m2), but who developed leukocytosis which was treated with hydroxyurea. Both patients demonstrated clinical and laboratory findings of disseminated intravascular coagulation, massive cell lysis manifested by marked increases in serum lactic dehydrogenase, and rapid clinical deterioration. Both patients developed bone marrow necrosis within viable, noninfarcted bone trabeculae. We postulate that the development of bone marrow necrosis in these two patients was not a chance occurrence. Rather, the specific combination of cytotoxic and differentiating agents used in these patients (hydroxyurea with all-trans retinoic acid) caused massive cell lysis and death. The absence of bone marrow necrosis in the setting of induction therapy for APL both with and without all-trans retinoic acid therapy suggests that the addition of hydroxyurea was critical to the development of marrow necrosis. We, therefore, recommend caution in the use of hydroxyurea and all-trans retinoic acid in the treatment of APL.

[Effect of various cytologic preparation techniques on form, texture and densitometric nuclear parameters of normal and dysplastic bladder urothelial cells]. / Einfluss verschiedener zytologischer Präparations-Methoden auf Form, Textur und densitometrische Kern-Parameter normaler und dysplastischer Zellen in Blasenspülflüssigkeiten.

An important prerequisite for densitometric and morphometric measurements on cytological specimens is the standardized cell preparation. Optimal results can only be achieved when the analyses are carried out on a regular monolayer of cell nuclei. Comparing the conventional cytological smear with a new centrifugation technique we demonstrate statistically significant differences of the two methods in texture, size and parameters describing the DNA content of normal and dysplastic urothelial cells.

[Fine-needle aspiration biopsy of the breast. Frequency, indication and accuracy, studied on material from the Cytological Laboratory of the Pathology Institute, St. Gallen Canton Hospital, 1981-1984]. / Feinnadelpunktion der Brustdrüse. Häufigkeit, Indikation und Treffsicherheit, untersucht am Material des Zytologischen Labors des Institutes für Pathologie, Kantonsspital St. Gallen, im Zeitraum 1981-1984.

1768 fine needle aspiration biopsies (FNAB) of the breast were evaluated between January 1981 and June 1984 at the Cytologic Laboratory, Institute of Pathology, Cantonal Hospital, St. Gall. The number of FNAB increased from 334 in 1981 to 837 in 1984. By far the most frequent indication for FNAB was a palpable lesion of the breast (in 92.1% of all cases). Other indications were radiological lesions without a palpable mass (2.7%), skin changes of the breast (1.7%) and, in a few cases, unilateral enlargement of the breast. Sensitivity and specificity of the method were calculated on the basis of two groups (A and B). In group A the FNAB was performed by a cytopathologist and in group B by general practitioners and specialists or hospital doctors. Sensitivity of 90.0% was calculated in group A and of 79.0% in group B. The specificity in the evaluated material was 100% for both groups. In group A, 5% of all carcinoma showed a false negative cytologic diagnosis, while in 9% of all FNAB the aspirated material was not representative. Most of the false negative diagnoses occurred with scirrhous carcinoma and with small carcinoma less than 1.5 cm in diameter. The percentage of the cases with a non-representative diagnosis reached 5% of all histologically proven carcinoma in group A and 19.2% in group B. The significantly higher percentage of non-representative diagnoses, together with a significantly lower sensitivity in group B (A: 90.0%, B: 79.0%) lead to the conclusion that the experience of the person who has performed the aspiration is of great importance for the diagnostic result.(ABSTRACT TRUNCATED AT 250 WORDS)

[Malignant pericardial effusion--a sign of unfavorable prognosis?]. / Maligner Perikarderguss--ein prognostisch ungünstiges Zeichen?

Malignant pericardial effusion (MPE) resulting in cardiac tamponade is a rare complication in neoplastic disease. From January 1975 to December 1984 the authors observed 22 patients with cytologically verified malignant pericardial effusion. The most frequent primary tumors were non-small cell lung cancer (6), breast cancer (5), non-Hodgkin lymphoma (4) and mesothelioma (4). 50% of the patients presented with MPE as the initial manifestation of the tumor. In the other group of patients MPE appeared after an average of 11 months following the diagnosis of malignant disease. The most frequent symptoms and clinical findings were dyspnea (100%), jugular venous distention (91%), and tachycardia (82%). During the first 24 hours after pericardiocentesis a median volume of 675 ml of predominantly serosanguinous effusion was drained. Besides intrapericardial drug instillation, patients also received local radiotherapy and systemic chemotherapy. At the time when MPE was diagnosed 77% of the patients exhibited advanced malignant disease. Mean survival time was 140 days. Malignant pericardial effusion is therefore regarded as an unfavorable prognostic factor.

Immunocytochemical characterization of lymphocytes in benign and malignant lymphocyte-rich serous effusions.

The cytological diagnosis of malignant Lymphoma in serous effusions can be difficult because reactive lymphocytes may be morphologically indistinguishable from malignant cells in lymphocytic and other low grade Non-Hodgkin's lymphomas. As a result of the present study, diagnostic accuracy can be improved by means of B- and T-cell enumeration using an immunoalkaline-phosphatase method (IAP). 30 cytological specimens, including 28 pleural, 1 pericardial and 1 ascitic fluids, were studied with a panel of monoclonal anti B- and anti T-cell antibodies (PAN B, kappa, lambda, T1, T2, OKT4, T8). Reactive lymphocytic effusions were characterized by a predominance of T cells constituting greater than or equal to 80% of all lymphocytes with an excess of helper/inducer cells (mean helper to suppressor ratio 3.0) and by a surface kappa to surface lambda ratio of 1.6 on B-cells. Tuberculous effusions showed a similar distribution of lymphocyte-subpopulations whilst most of the carcinomatous fluids showed a lower percentage of T cells (lowest value 67%) and lower Th: Ts ratio (mean 2.0). Lymphoid cells in samples of five B-cell lymphomas were characterized by T-cell depression (less than 70%). B-cells in three cases expressed clear cut light chain monoclonality which was at least suggested in the other two cases. Lymphoid cells from two cases of Hodgkin's disease expressed an indistinct immunological pattern. Labelling of cytoplasmic immunoglobulins (heavy and light chains) using the peroxidase antiperoxidase method (PAP) may be important to characterize neoplasms of the plasma cell series. It is concluded that the chosen panel of antibodies in combination with IAP labelling method may be of great value in identifying B-cell lymphomas. The technique can be used in the routine laboratory and storage of unlabelled and labelled slides over long periods is possible.

Identification of types and primary sites of malignant tumors by examination of exfoliated tumor cells in serous fluids. Comparison with the diagnostic accuracy on small histologic biopsies.

The accuracy of identification of tumor type and primary site of malignant tumors by examination of exfoliated tumor cells was cytologically studied in 448 malignant effusions from 366 patients for whom the primary tumor site had been confirmed by histology. Ninety-seven corresponding small biopsies from metastases were separately reviewed histopathologically. In four fluids, the cells were too scanty or too poorly preserved for tumor typing. The cytologic tumor typing was performed with nearly 100% accuracy in the remaining 444 fluids, except for those of intermediate-cell anaplastic carcinomas (0 of 3) and poorly differentiated squamous (epidermoid) carcinomas (1 of 5). Adenocarcinoma was correctly identified in 98% of 285 fluids, large-cell carcinoma in 97% of 108 fluids, oat-cell carcinoma in 94% of 16 fluids, well-differentiated (keratinizing) squamous carcinoma in 100% of 3 fluids, malignant lymphoma in 100% of 22 fluids and sarcoma in 100% of 2 fluids. The criteria and the failures are discussed at length. In the investigation of the accuracy of cytologic and histologic diagnoses with respect to the primary tumor site, tumors with variable sites of origin (sarcomas and lymphomas) and those with usually singular sites of origin (e.g., small-cell anaplastic carcinoma of the lung) were excluded, leaving 387 cytologic and 83 histologic specimens available for review. The breast as a primary site was correctly identified in 70% of both the cytologic and histologic specimens; the primary cytodiagnostic criteria included a uniform cell pattern, finely granular chromatin, dense cytoplasm and cell balls with smooth borders. Ovarian primaries were correctly identified in 70% of the fluids and 83% of the biopsy samples on the basis of very irregular clusters of large pleomorphic tumor cells, large nucleoli and psammoma bodies. Lung primaries, identified in 50% of the fluids and 29% of the biopsy samples, showed quite variable cell patterns, most often including large pleomorphic cells with or without mucus formation and prominent multinucleation. Gastric cancers of the diffuse type were accurately identified in 52% of the corresponding fluids, which showed mainly isolated cells with dense cytoplasmic rims, occasional signet-ring cells, "embryo-shaped" nuclei, marked hyperchromasia and densely granular chromatin.(ABSTRACT TRUNCATED AT 400 WORDS)

The value of cytology for the follow-up of prostatic cancer after hormone and irradiation therapy.

In a prospective study 162 patients with localized or metastasizing carcinoma of the prostate were followed by fine-needle biopsies for cytological control of the therapy. 74 patients were treated by external beam irradiation (6,000-7,000 cGy rotation technique), 88 patients by hormone therapy. Cytologic regression grading was correlated with the clinical course during 3-6 years. The study shows a good correlation between the cytologic regression grade 1 year after irradiation and the clinical course. A poor regression grade (still visible tumor cells) 1 year after irradiation was followed by rapid tumor progression in more than 70%. In these cases early introduction of additional therapy should be considered. After hormone therapy the correlation of the cytologic regression grade with the clinical course is lower. Marked cytologic regression was associated with rapid tumor progression in about 60%, while poor regression grading was followed in about 50% by a satisfactory course. Fine-needle aspiration biopsy and grading of cytological regression is useful for follow-up of prostatic cancer after irradiation therapy. After hormone treatment, the grade of cytological regression does not reflect the prognosis of the disease sufficiently, thus other clinical, enzymatic and scintigraphic parameters have to be examined especially in cases with primary evidence of a metastasizing cancer of the prostate.

[Rheumatoid body cavity effusions in chronic polyarthritis. 5 cases with special reference to cytopathology]. / Rheumatische Körperhöhlenergüsse im Verlauf von chronischer Polyarthritis. 5 Fälle mit besonderer Berücksichtigung der Zytopathologie.

All of 5 patients with rheumatoid disease presented with the rare complication of rheumatoid pleurisy or pericarditis. The lesion was diagnosed cytologically from effusions by means of the characteristic cellular findings. The unique cytologic picture and possible differential diagnoses are presented in detail. The pathogenesis of rheumatoid serositis and its bearing on follow-up of rheumatoid disease are discussed.

The clinical spectrum and treatment of Lyme disease.

Lyme disease was recognized as a separate entity because of close geographic clustering of affected children in Lyme, Connecticut, with what was thought to be juvenile rheumatoid arthritis. It then became apparent that Lyme disease is a complex, multisystem disorder. The illness usually begins in summer with erythema chronicum migrans and associated symptoms (stage 1). Weeks to months later, some patients develop neurologic or cardiac abnormalities (stage 2), and weeks to years later, many patients develop intermittent attacks of arthritis (stage 3), which may become chronic, with erosion of cartilage and bone. Patients with severe and prolonged illness have an increased frequency of the B-cell alloantigen, DR2. For patients with early Lyme disease, tetracycline appears to be the most effective drug, then penicillin, and finally erythromycin. High-dose intravenous penicillin is effective for the later stages of the disease.