Biomedical subjects

Theo van der Kwast

Publications and source records attributed to Theo van der Kwast.

3 recordsLinked to original sources

PubMed2006

Discrimination between nontumor bladder tissue and tumor by Raman spectroscopy.

We have applied Raman spectroscopy to discriminate between nontumor and tumor bladder tissue and to determine the biochemical differences therein. Tissue samples from 15 patients were collected, and frozen sections were made for Raman spectroscopy and histology. Twenty-five pseudocolor Raman maps were created in which each color represents a cluster of spectra measured on tissue areas of similar biochemical composition. For each cluster, the cluster-averaged spectrum (CAS) was calculated and classified as tumor and nontumor in accordance to pathohistology. Unguided hierarchical clustering was applied to display heterogeneity between and within groups of nontumor and tumor CAS. A linear discriminant analysis model was developed to discriminate between CAS from tumor and nontumor. The model was tested by a leave-one-patient-out validation, 84 of the 90 CAS (93%) were correctly classified with 94% sensitivity and 92% specificity. Biochemical differences between tumor and nontumor CAS areas were analyzed by fitting spectra of pure compounds to the CAS. Nontumor CAS showed higher collagen content while tumor CAS were characterized by higher lipid, nucleic acid, protein, and glycogen content. Raman spectroscopy enabled effective discrimination between tumor and nontumor bladder tissue based on characterized biochemical differences, despite heterogeneity expressed in both tumor and nontumor CAS.

Cluster Analysis↗

PubMed2005

Web-based virtual microscopy in teaching and standardizing Gleason grading.

Gleason grading forms the basis of prognostic and therapeutic assessment in prostatic carcinoma despite its subjective nature and substantial interobserver variation. The accuracy of Gleason grading can be improved by the use of educational tools such as reference images. However, conventional microscopy images are of limited educational value because it is neither possible to view the sample at different magnifications nor to navigate into different areas of the specimen. This limitation can be overcome by the use of virtual microscopy, which allows viewing entire digitized microscope slides. We created an interactive Web site ( www.webmicroscope.net/gleason ) featuring a comprehensive set of prostatic needle biopsies as virtual slides, which can be viewed with a standard Web browser (Internet Explorer or Netscape). To evaluate the validity of Web-based virtual microscopy for Gleason grading, an experienced uropathologist (TK) scored a series of 62 biopsies from the original glass slides and 6 weeks later from virtual slides on the Web site using an ordinary desktop computer. The intraobserver agreement was excellent, with identical Gleason scores found in 48 of the 62 cases ( kappa = 0.73). The 14 remaining scores differed only by 1 point on the Gleason scale (2-10). The virtual slides were viewed by 2 other uropathologists (PM and HH), with interobserver kappa coefficients ranging from 0.55 to 0.62, which is within the range of previously reported studies using glass slides. The 3 uropathologists' Gleason scores were included as reference scores on the Web site, which now serves as a publicly open platform for self-testing and learning of Gleason grading. We conclude that Web-based virtual microscopy is a promising new tool for teaching and standardizing Gleason grading.

Biopsy, Needle↗

PubMed2002

A BRCA1/2 mutation, high breast density and prominent pushing margins of a tumor independently contribute to a frequent false-negative mammography.

Female BRCA1/2 mutation carriers develop in up to 50% breast cancer (BC) before age 50 years. We investigated whether the specific histologic features of BRCA1/2-associated breast cancer influence imaging. We correlated the mammographic results with the histology of 34 BC in BRCA1/2 mutation carriers and 34 sporadic cancers in patients, matched for age and year of diagnosis. Mammography was significantly more frequently false-negative in carriers than controls (62% vs. 29% p = 0.01), despite comparable tumor size (mean solidus in circle 1.51 vs. 1.75) and breast density (high 41% vs. 53%). The image in carriers was significantly less as spiculated mass (6 vs. 18 p = 0.01). Cancers of BRCA1/2 mutation carriers had frequently higher mitotic counts (p < 0.0001) and prominent pushing margins around the tumor (p = 0.08) (p = 0.05 for 32 BRCA1). We also observed that prominent "pushing margins" correlated significantly with a false-negative mammography (p = 0.005) and with a mammographic image of a smooth, not a spiculated, mass (p = 0.01). False-negative mammography correlated independently with: BRCA1/2 mutation (p = 0.02), prominent pushing margins (p = 0.03) and high breast density (p = 0.01). MRI was carried out in 12 carriers, had 100% sensitivity and detected 5 cancers, still occult at physical examination and mammography. A BRCA1/2 mutation and high breast density at mammography contribute independently to false-negative mammography results. In mutation carriers any mammographic mass must be regarded with suspicion. Pushing margins of the tumor partly explain these results. For early BC detection in mutation carriers additional methods like MRI may be needed. This may not be necessary in other young women with breast symptoms.

Adult↗