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L Egevad

Publications and source records attributed to L Egevad.

31 records · Page 2Linked to original sources
PubMed1999

Biopsy protocol stability in a three-dimensional model of prostate cancer: changes in cancer yield after adjustment of biopsy positions.

OBJECTIVES: Transrectal ultrasound-guided prostate biopsies are often taken according to a systematic, standardized schedule. The diagnostic stability of this system was evaluated by moving the biopsies in a three-dimensional (3D) model. METHODS: A computerized 3D reconstruction was made from each of 75 radical prostatectomy specimens. Simulated core biopsies imitated a standardized 10-biopsy protocol, including sextant biopsies. In total, 30,000 biopsies were generated by moving the standardized biopsies 1, 2, 3, and 4 mm (parallel needle shifts) or 5 degrees, 10 degrees, 15 degrees, and 20 degrees(rotation of the needle tip) in a random direction. RESULTS: The diagnosis of the individual biopsy changed from cancer to benign or vice versa in 4.9% to 1 5.7% after 1 to 4-mm parallel needle shifts and 2.0% to 7.5% after 5 degrees to 20 degrees rotations. The corresponding figures for the final diagnosis of the 10-biopsy set were 0.8% to 9.6% and 0.5% to 3.2%. Transition zone biopsies containing cancer changed to benign more often than the other biopsies (P <0.001). Parallel needle shifts of 2 mm changed the diagnosis more often than the 15 degrees rotation (9.4% and 5.9%, respectively, P <0.001), although conveying the same overall needle shift. CONCLUSIONS: The cancer yield of prostate biopsies is influenced even by small changes in needle positions. The transition zone biopsies are most likely to change from cancer to benign when moved. Changing the insertion point of the needle has a higher impact on cancer yield than rotating the tip.

Adult↗
PubMed1999

Modeling prostate cancer distributions.

OBJECTIVES: To use computer-assisted three-dimensional (3D) reconstruction to study cancer distribution in the prostate. The distributions have been determined using data from 81 prostates surgically removed because of cancer. METHODS: The pattern of distribution was determined by reshaping (morphing) all prostates in the same size category (small, medium, large) into the same shape and by overlayering the 3D distribution of all cancers into a "unit prostate." Also, the pattern of 3D distribution was defined for small, medium, and large volume cancers. RESULTS: The study yielded a clear, visual "scatter diagram" representation of the statistics of prostate cancer distribution. It confirmed previous general knowledge: small cancers are mainly found in the lower one third and principally in the dorsolateral part of the gland. CONCLUSIONS: This report is part of the investigations preliminary to establishing an optimal protocol for needle biopsy of prostate cancer.

Adult↗
PubMed1998

Estimation of prostate cancer volume by multiple core biopsies before radical prostatectomy.

OBJECTIVES: To investigate whether tumor volume, an important prognostic factor in prostate cancer, could be estimated from the amount of cancer in multiple core biopsies. METHODS: In 80 men, transrectal ultrasound-guided biopsies were taken from focal lesions detected by ultrasound and 8 to 10 standardized positions, including sextant biopsies (apex, midmedial, base) and midlateral and transition zone biopsies. The cancer length in the biopsies was measured. After radical prostatectomy, the prostates were totally embedded, whole-mounted, and tumor volume was measured planimetrically. RESULTS: The tumor volume correlated significantly with the total cancer length of all biopsies (r = 0.56) and of the sextant biopsies (r = 0.39). It was found that midlateral and transition zone biopsies provided independent information when included in a multiple regression model with tumor volume as the dependent variable and the sextant biopsies as explanatory variables. All men (n = 6) with less than 3 mm cancer length in only one positive biopsy and a Gleason score less than 7 had a tumor volume less than 1 mL. Nine of 10 men with less than 7 mm of cancer in one positive biopsy and Gleason score less than 7 had tumors smaller than 1 mL. Sextant biopsies did not reliably predict cancer volumes less than 1 mL. CONCLUSIONS: The cancer yield of 8 to 10 biopsies correlated better with the volume of prostate cancer than sextant biopsies. This extended biopsy protocol could be used to predict cancers of less than 1 mL in volume.

Adult↗
PubMed1998

Precancer of the prostate.

The evolution of the malignant phenotype requires a set of genetic and epigenetic changes in sets of genes responsible for regulation of normal growth and cell death, of "social behaviour" and differentiation. The sum of these changes, not only the sequence, determines the malignancy as well as its grade. The probability of invasiveness shows a remarkable relationship to morphological changes, which in turn prove to be accompanied by a multitude of discrete molecular perturbations. Some of these can be characterized as functional, others as inductive with respect to their participation in the process. Since only the functional changes regulate malignant behaviour per se, it is an important task for future research to assemble a set of such changes, find markers for them and combine morphological and molecular indicators to achieve prognostically optimal scores. It should be emphasized, though, that rational use of such scores using biopsy samples as a source of information cannot be defined until biopsy strategies have been standardized and optimized.

Biopsy↗
PubMed1997

Expression of p21 and mutant p53 gene products in residual prostatic tumor cells after radical radiotherapy.

BACKGROUND: In a previous study, sextant core biopsies revealed residual tumor in the prostate in 37/55 investigated patients, with an average of 6.8 years after external beam radiation therapy (RRT). More than half of the biopsies exhibited Ki-67 and PCNA proliferation activity. METHODS: The present study aims at further characterizing residual tumor cells post-RRT by investigating whether the tumor cells exhibit immunohistochemical expression of p21 and mutant p53 gene products, which reflect the state of cell cycle regulatory mechanisms. RESULTS: Positive p53 staining was observed in 11% and p21 positivity in 47% of biopsies. The proportion of positively stained cells was low for both antigens. The staining patterns point to the existence of wild-type p53-dependent, as well as alternative pathways for p21 protein induction. CONCLUSIONS: A low proportion of tumor cells exhibited p53 protein accumulation post-RRT. G1 arrest, as assessed by p21 immunoexpression, was demonstrated in a low percentage of tumor cells in < 50% of post-RRT biopsies, indicating that the vast majority of residual tumor cells following RRT escape the G1/S checkpoint control and propagate into S-phase, presumably with a maintained malignant potential.

Adenocarcinoma↗
PubMed1997

The sextant protocol for ultrasound-guided core biopsies of the prostate underestimates the presence of cancer.

OBJECTIVES: The aim of this prospective study was to evaluate the sensitivity of the sextant biopsy protocol compared with a more extensive procedure for the detection of prostate cancer and to define a biopsy model with the minimal number of biopsies necessary to maintain diagnostic accuracy. METHODS: A total of 512 consecutive patients with suspected prostate cancer were examined with transrectal ultrasound (TRUS) and underwent TRUS-guided core biopsy. All patients had 8 or 10 standardized biopsy samples taken, with the number depending on the size of the gland. Additional biopsy samples were taken from hypoechoic or hyperechoic lesions located outside the predetermined location for the standardized biopsies (ie, target biopsies). The sensitivity of the detection of cancer for different combinations of biopsy samples was analyzed and compared with that of our model with 8 to 10 biopsies. RESULTS: In all, 276 cancers were detected, of which 88 (32%) had an isoechoic appearance. Sensitivity was 59% for focal lesions detected by TRUS, 85% to 97% for different combinations of systematic biopsy samples, and 93% to 98% for a combination of systematic and target biopsy samples. The sensitivity for the standard sextant protocol was 85%. By adding target biopsies, the sensitivity increased to 93%. CONCLUSIONS: The standard sextant protocol leaves 15% of cancers undetected compared with results obtained from a more extensive biopsy procedure. By combining systematic and target sampling, the sensitivity increases; however, a major concern is that the clinical importance of cancers detected by multiple biopsies needs to be evaluated.

Adult↗
PubMed1997

A new method for segmentation of colour images applied to immunohistochemically stained cell nuclei.

A new method for segmenting images of immunohistochemically stained cell nuclei is presented. The aim is to distinguish between cell nuclei with a positive staining reaction and other cell nuclei, and to make it possible to quantify the reaction. First, a new supervised algorithm for creating a pixel classifier is applied to an image that is typical for the sample. The training phase of the classifier is very user friendly since only a few typical pixels for each class need to be selected. The classifier is robust in that it is non-parametric and has a built-in metric that adapts to the colour space. After the training the classifier can be applied to all images from the same staining session. Then, all pixels classified as belonging to nuclei of cells are grouped into individual nuclei through a watershed segmentation and connected component labelling algorithm. This algorithm also separates touching nuclei. Finally, the nuclei are classified according to their fraction of positive pixels.

Algorithms↗
PubMed1997

Differential gene expression of steroid 5 alpha-reductase 2 in core needle biopsies from malignant and benign prostatic tissue.

Androgens are implicated in the development of prostate cancer (CAP) and benign prostate hyperplasia. The conversion of testosterone to the more potent metabolite dihydrotestosterone by prostatespecific steroid 5 alpha-reductase type 2 (5 alpha-red2) is a key mechanism in the action of androgens in the prostate and is important in the promotion and progression of prostate diseases. Manipulation of the turnover of androgens is thus fundamental in the pharmacological treatment strategy. We have developed a sensitive solution hybridization method for quantification of the gene expression of 5 alpha-red2 in core needle biopsies of the prostate. The 5 alpha-red2-specific messenger RNA (mRNA) levels were measured in 50 human prostate transrectal ultrasound-guided core biopsies obtained from 31 outpatients (median age 72, range 67-88 yr) undergoing biopsy for diagnostic purposes. Significant differences were observed in the gene expression of 5 alpha-red2 between cancerous and noncancerous tissue. In the 14 biopsies judged cancerous, the median 5 alpha-red mRNA levels were 3.5 amol/ng total RNA compared with 12.0 amol/ng total RNA in the biopsies showing no cancer (P = 0.0018). The median 5 alpha-red2 mRNA level in noncancerous tissue was thus 3.4 times higher than in the cancerous specimens.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1996

Assessment of proliferation indicators in residual prostatic adenocarcinoma cells after radical external beam radiotherapy.

BACKGROUND: Fifty-five patients who had received radical external beam radiotherapy (RRT) for clinically staged, localized prostatic adenocarcinoma were examined with systematic sextant mapping with the help of transrectal ultrasound-guided core biopsies. The average follow-up after RRT was 6.8 years. Residual cancer was found histopathologically in 67% (37/55) of the patients investigated. METHODS: In the present report, the viability of these tumor cells was studied using immunohistochemical staining methods with the monoclonal antibodies MIB1 and PC10, which are specific for the proliferation-associated antigens Ki-67 and PCNA. RESULTS: Available data concerning proliferating activity in the pretreatment situation in 12 of these patients revealed that proliferating activity was substantially reduced in the majority of cases after RRT. Post-RRT, Ki-67, and PCNA activity was nonetheless found to varying degrees in 64% and 94% of the 36 evaluable tumor-harboring specimens, respectively. In the majority of cases, the proportion of proliferating cells, designated "score", was low. However, Ki-67 scores of up to 8% and PCNA scores of up to 50% were obtained in 35% (8/23) and 97% (33/34) of the specimens, respectively, with proliferative activity. There was no significant correlation between tumor grade and proliferative score in the follow-up biopsies. In the 36 cases investigated, endocrine treatment did not influence the proliferation results. CONCLUSIONS: The present study demonstrates a proliferative capacity in residual tumor cells in a long-term follow-up after RRT, suggesting that these cancer cells might have a biological significance.

Adenocarcinoma↗
PubMed1996

Multiple transrectal ultrasound-guided biopsies for the detection of prostate cancer and determination of tumor volume, grade, and seminal vesicle invasion.

A total of 251 men with suspected prostate cancer were examined by transrectal ultrasound (TRUS) in order to evaluate the usefulness of TRUS and core biopsies for the detection of prostate cancer and determination of tumor volume, grade, and seminal vesicle invasion (SVI). Biopsies targeting hypoechoic lesions were taken in combination with systematic biopsies obtained from six standardized locations. Bilateral seminal vesicle biopsies were obtained from 168 of the men. A total of 26 patients underwent surgery and a comparison between the results of the histopathological evaluation of core biopsies and the prostatectomy specimen was performed. A total of 137 cancers were detected. In 34 patients (25%) the tumors were diagnosed by systematic biopsies alone. Tumor volume as estimated by TRUS underestimated the volume when compared to a planimetric technique. Correlation between the two methods was not found by regression analysis. Systematic biopsies did not improve grading compared to the grading of prostatectomy specimens. A total of 24 SVIs were detected. Valuable information was obtained for the diagnosis of prostate cancer by taking systematic biopsies.

Adult↗
PubMed1995

Transrectal ultrasonically-guided core biopsies in the assessment of local cure of prostatic cancer after radical external beam radiotherapy.

Fifty-five patients were included in an extended follow-up after radical radiation therapy (RRT) for localized prostatic cancer (T1-3, Nx, M0). Local cure was assessed by a combination of digital rectal examination (DRE), transrectal ultrasound (TRUS) and systematic 'mapping' with TRUS-guided core biopsies (TGCB). After a mean follow-up of 6.8 years, 33% (18/55) of the patients were locally free of tumour, while in 67% (37/55) of cases residual cancer was demonstrated in the biopsies. Endocrine treatment did not influence the local cure rate, nor did the T stage of tumour grade at diagnosis or the cumulative radiation effect (CRE) values within the range of the present study. The sensitivity of DRE and TRUS was low; 37% and 20% respectively, while the specificity of the DRE and TRUS methods was 83% and 94% respectively. The conclusion of the study is that residual tumour was found in the high proportion of biopsied patients nearly 7 years after RRT and that multiple, TRUS-guided core biopsies are mandatory in the assessment of local cure in patients irradiated for prostatic cancer; both DRE and TRUS on their own are less reliable.

Biopsy↗
PubMedDate not supplied

Three-dimensional modeling of biopsy protocols for localized prostate cancer.

Prostate cancer is the most common malignant tumor in American men, yet only a small percentage of men will develop clinically significant disease. Needle core biopsies are used to confirm the presence of cancer prior to surgery. While needle core biopsies have shown some ability to predict tumor volume and grade in prostatectomy specimens, for the individual patient they are neither sensitive nor specific enough to guide therapy. In this paper, we describe a system for simulating needle biopsies on three-dimensional models of cancerous prostates reconstructed from serial sections. First we segment the serial sections, delineating tumors and landmarks. Next, we register the sections using a color-merging scheme, and reconstruct the three-dimensional model using modified-shape-based interpolation. The resulting volume can be rendered, and simulated needle core biopsies can be taken from the reconstructed model. We use our system to simulate two different biopsy protocols on a reconstructed prostate specimen.

Biopsy, Needle↗