Ein Plädoyer für die Zytopathologie

Zusammenfassung: Im Vergleich zu anderen europäischen und außereuropäischen Ländern werden die Möglichkeiten der Zytopathologie in der Tumordiagnostik an vielen deutschen Pathologie-Instituten traditionell nicht wahrgenommen. Dabei liefern sie gerade dort, wo immunchemische und molekularbiologische Zusatzuntersuchungen angezeigt sind, wertvolles Zellmaterial. Auf vielen Organgebieten kann die Zytologie die histologischen Untersuchungen ergänzen und manche operativen Eingriffe überflüssig machen. Eine Verbesserung der bedauerlichen Situation ist nur möglich, wenn der Zytologie in der Fachausbildung zum Pathologen ein höherer Stellenwert eingeräumt wird. Dies wiederum erfordert organisatorische und infrastrukturelle Veränderungen innerhalb der pathologischen Institute. Dabei sollten die universitären Institute als wichtige Ausbildungsstätten vorangehe

Zytologie der ableitenden Harnwege: Zwischen Zweifel und Gewissheit

Zusammenfassung: Wenig differenzierte Urothelkarzinome und das bioptisch oft schwierig fassbare Carcinoma in situ lassen sich im Gegensatz zu den "low-grade" urothelialen Neoplasien in der Urinzytologie zuverlässig diagnostizieren. Wir empfehlen folgendes Klassifikationssytem: negativ, zweifelhaft, suspekt und positiv. Angesichts der komplexen klinisch-pathologischen Zusammenhänge sollte die Klassifikation stets von einem Kommentar begleitet sein. Die 2004 WHO-Klassifikation der urothelialen Tumoren stellt die klinisch weniger relevanten "Low-grade-Tumoren" den klinisch relevanten "High-grade-Tumoren" gegenüber, die sich zytologisch meist als "positiv" klassifizieren lassen. Die zytologische Diagnose der zystoskopisch meist sichtbaren Low-grade-Neoplasien ist klinisch nicht dringlich. Urotheliale Neoplasien zeichnen sich im Gegensatz zu reaktiven Veränderungen durch chromosomale Aberrationen aus. Fluoreszenz-in-situ-Hybridisierung (FISH) mit mehreren DNS-Sonden eignet sich deshalb für die Abklärung unklarer Befunde. Bei eindeutig positiver Zytologie ist eine FISH-Untersuchung dagegen nicht notwendig. Eine standardisierte Diagnoseformulierung und die Möglichkeit zu weiteren Abklärungen mittels FISH erhöhen den diagnostischen Stellenwert der Harntraktzytologi

Invasive pulmonary aspergillosis: effects of early resection in a neutropenic rat model

Objective: Invasive pulmonary aspergillosis is frequent in neutropenic patients. Usually localized in the beginning, the disease spreads and mortality is high despite antifungal treatment. The role of early adjuvant surgery is not clear. Surgery may help to confirm fungal disease, may control fungal disease locally and may prevent systemic spreading. This study examines effects of early resection on survival and dissemination in a rat model of localized invasive pulmonary aspergillosis. Methods: Forty persistently neutropenic male albino rats were challenged with standardized conidial aspergillus inoculum injected into peripheral lung tissue of the right upper lobe under direct vision. Animals were divided into four groups. Twenty animals were treated with amphotericin B at 1 mg/kg per day beginning 48 h after inoculation, 20 animals were left untreated. In each group half the animals underwent early resection of localized invasive aspergillosis by lobectomy. Animals were checked daily and mortality was recorded up to 28 days after which surviving animals were sacrificed. Results: Significantly higher survival was observed in resected animals in the non-Am B groups (survival: 10±19% without early resection and 50±32% with early resection; P=0.044). However, early resection did not lead to improved survival in animals treated with amphotericin B (survival 70±29% without early resection and 50±32% with early resection; P=0.316). Conclusions: In this rat model of localized invasive pulmonary aspergillosis effects of early resection on survival could be demonstrated only in animals not receiving amphotericin B treatmen

Who Watches the Watchmen? An Appraisal of Benchmarks for Multiple Sequence Alignment

Multiple sequence alignment (MSA) is a fundamental and ubiquitous technique in bioinformatics used to infer related residues among biological sequences. Thus alignment accuracy is crucial to a vast range of analyses, often in ways difficult to assess in those analyses. To compare the performance of different aligners and help detect systematic errors in alignments, a number of benchmarking strategies have been pursued. Here we present an overview of the main strategies--based on simulation, consistency, protein structure, and phylogeny--and discuss their different advantages and associated risks. We outline a set of desirable characteristics for effective benchmarking, and evaluate each strategy in light of them. We conclude that there is currently no universally applicable means of benchmarking MSA, and that developers and users of alignment tools should base their choice of benchmark depending on the context of application--with a keen awareness of the assumptions underlying each benchmarking strategy.Comment: Revie

Aneuploidy and prognosis of non-small-cell lung cancer: a meta-analysis of published data

In lung cancer, DNA content abnormalities have been described as a heterogeneous spectrum of impaired tumour cell DNA histogram patterns. They are merged into the common term of aneuploidy and probably reflect a high genotypic instability. In non-small-cell lung cancer, the negative effect of aneuploidy has been a subject of controversy inasmuch as studies aimed at determining the survival–DNA content relationship have reported conflicting results. We made a meta-analysis of published studies aimed at determining the prognostic effect of aneuploidy in surgically resected non-small-cell lung cancer. 35 trials have been identified in the literature. A comprehensive collection of data has been constructed taking into account the following parameters: quality of specimen, DNA content assessment method, aneuploidy definition, histology and stage grouping, quality of surgical resection and demographic characteristics of the analysed population. Among the 4033 assessable patients, 2626 suffered from non-small-cell lung cancer with aneuploid DNA content (overall frequency of aneuploidy: 0.65; 95% CI: (0.64–0.67)). The DerSimonian and Laird method was used to estimate the size effects and the Peto and Yusuf method was used in order to generate the odds ratios (OR) of reduction in risk of death for patients affected by a nearly diploid (non-aneuploid) non-small-cell lung cancer. Survivals following surgical resection, from 1 to 5 years, were chosen as the end-points of our meta-analysis. Patients suffering from a nearly diploid tumour benefited from a significant reduction in risk of death at 1, 2, 3 and 4 years with respective OR: 0.51, 0.51, 0.45 and 0.67 (P< 10−4for each end-point). 5 years after resection, the reduction of death was of lesser magnitude: OR: 0.87 (P = 0.08). The test for overall statistical heterogeneity was conventionally significant (P< 0.01) for all 5 end-points, however. None of the recorded characteristics of the studies could explain this phenomenon precluding a subset analysis. Therefore, the DerSimonian and Laird method was applied inasmuch as this method allows a correction for heterogeneity. This method demonstrated an increase in survival at 1, 2, 3, 4 and 5 years for patients with diploid tumours with respective size effects of 0.11, 0.15, 0.20, 0.20 and 0.21 (value taking into account the correction for heterogeneity;P< 10−4for each end-point). Patients who benefit from a surgical resection for non-small-cell lung cancer with aneuploid DNA content prove to have a higher risk of death. This negative prognostic factor decreases the probability of survival by 11% at one year, a negative effect deteriorating up to 21% at 5 years following surgery. © 2001 Cancer Research Campaign http://www.bjcancer.co

Standardised Benchmarking in the Quest for Orthologs

The identification of evolutionarily related genes across different species—orthologs in particular—forms the backbone of many comparative, evolutionary, and functional genomic analyses. Achieving high accuracy in orthology inference is thus essential. Yet the true evolutionary history of genes, required to ascertain orthology, is generally unknown. Furthermore, orthologs are used for very different applications across different phyla, with different requirements in terms of the precision-recall trade-off. As a result, assessing the performance of orthology inference methods remains difficult for both users and method developers. Here, we present a community effort to establish standards in orthology benchmarking and facilitate orthology benchmarking through an automated web-based service (http://orthology.benchmarkservice.org). Using this new service, we characterise the performance of 15 well-established orthology inference methods and resources on a battery of 20 different benchmarks. Standardised benchmarking provides a way for users to identify the most effective methods for the problem at hand, sets a minimal requirement for new tools and resources, and guides the development of more accurate orthology inference methods