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Contains fulltext : 71387.pdf (Publisher’s version ) (Open Access), BACKGROUND: Not all patients with locally advanced rectal cancer (LARC) respond equally to neo-adjuvant radiochemotherapy (RCT). Patients with highly apoptotic less advanced rectal cancers do not benefit from short-term radiotherapy. This study investigates whether this is also the case in the setting of RCT for LARC. PATIENTS AND METHODS: Tissue microarrays were constructed of biopsy and resection specimens of 201 LARC patients. Apoptosis (M30) and several apoptosis-regulating proteins [p53, Bcl-2, Bax, cyclooxygenase-2 (Cox-2) and mamma serine protease inhibitor (maspin)] were studied with immunohistochemistry. Subsequently, predictive values for local recurrence (LR), overall survival (OS) and histological tumour regression were analysed. RESULTS: Apoptotic levels, quantified as the number of apoptotic cells/mm(2) tumour epithelium, were higher in posttherapy tissues compared with biopsies (P < 0.001). Biopsies from clinical T4 stage tumours demonstrated significantly higher levels of apoptosis than clinical T3 stage tumours (P = 0.020). Therapy-induced apoptosis was higher when the interval between the last day of irradiation and surgery increased (P < 0.001, correlation coefficient = 0.355). Pre- and posttherapy apoptosis, p53, Bcl-2, Bax and Cox-2 were not associated with LR, OS or tumour regression. Intense pretherapy cytoplasmatic staining of maspin indicated a higher risk on LR (P = 0.009) only. CONCLUSION: Combined RCT is also successful in highly apoptotic tumours and is therefore independent of intrinsic apoptosis.

Contains fulltext : 51438.pdf (Publisher’s version ) (Open Access), Lichen sclerosus, high-grade usual vulvar intraepithelial neoplasia (VIN) and differentiated VIN have a different malignant potential. The objective of this study was to quantify the proliferative activity in the basal region of the epithelium of vulvar premalignancies. Furthermore, we investigated whether MIB1 expression in the basal region of vulvar epithelium can be helpful in diagnosing differentiated VIN, which may be hard to discern from normal epithelium. MIB1 was used to immunohistochemically visualise proliferating cells within formalin-fixed, paraffin-embedded, archival tissue sections of different vulvar premalignancies (N=48) and normal vulvar epithelium (N=16). Automatic digital image analysis software was developed to quantify the proliferating fraction in different parts of the epithelium (MIB1 positivity index). MIB1 expression differed among the various vulvar premalignancies; a MIB1-negative basal cell layer was a distinct feature of normal vulvar epithelium. No MIB1-negative basal cell layer was noted in differentiated VIN or other vulvar premalignancies. Owing to this negative cell layer, the MIB1 proliferation index in normal vulvar epithelium was significantly lower than in vulvar premalignancies. In conclusion, MIB1 expression can be a helpful tool in diagnosing a premalignancy and has additional value especially to distinguish differentiated VIN neoplasia from normal vulvar epithelium, but cannot explain the differences in malignant potential.

Contains fulltext : 53220.pdf (publisher's version ) (Open Access), Objective and reproducible assessment of cancer biomarkers may be performed using rare event detection systems. Because many biomarkers are not true 'rare events', in this study a semi-rare event detection system was developed. The system is capable of assigning a discriminant score to detected positive cells, expressing the extent and intensity of the immunocytochemical staining. A gallery image is constructed showing the diagnostically most interesting cells as well as quantitative data expressing the biomarker staining pattern. To increase scanning speed, an adaptive scanning strategy is studied in which scanning is aborted when a sufficient number of positive cells has been identified. System performance was evaluated using liquid based cervical smears, stained with an antibody directed against p16(INK4a) tumor suppressor protein. Overexpression of p16(INK4a) in cervix is related to high-risk HPV infection, which is associated with carcinogenesis. Reproducibility of the system was tested on specimens containing limited positivity. Quantitative analysis was evaluated using 10 cases within normal limits and 10 high grade lesions. The system was highly reproducible in detecting positive cells and in calculating discriminant scores (average CV 0.7%). Quantitative features were significantly increased in high grade lesions (p<0.001). Adaptive scanning decreased scanning time with only minor impact on scanning results. The system is capable of automated, objective and reproducible assessment of biomarker expression and may be useful for a variety of applications.

Contains fulltext : 49465.pdf (Publisher’s version ) (Open Access), The magnification factor in transmission electron microscopy is not very precise, hampering for instance quantitative analysis of specimens. Calibration of the magnification is usually performed interactively using replica specimens, containing line or grating patterns with known spacing. In the present study, a procedure is described for automated magnification calibration using digital images of a line replica. This procedure is based on analysis of the power spectrum of Fourier transformed replica images, and is compared to interactive measurement in the same images. Images were used with magnification ranging from 1,000 x to 200,000 x. The automated procedure deviated on average 0.10% from interactive measurements. Especially for catalase replicas, the coefficient of variation of automated measurement was considerably smaller (average 0.28%) compared to that of interactive measurement (average 3.5%). In conclusion, calibration of the magnification in digital images from transmission electron microscopy may be performed automatically, using the procedure presented here, with high precision and accuracy.

Contains fulltext : 47618.pdf (Publisher’s version ) (Open Access), OBJECTIVE: The increased perinatal morbidity in diabetes may be partly related to vascular dysfunction. Because potassium channels play an important role in the regulation of vascular tone, this study explores the impact of diabetes on potassium channel function in the fetoplacental vascular bed. STUDY DESIGN: Vascular potassium channel function was investigated by ex vivo dual perfusion of isolated placental cotyledons (n = 47). Appropriate control experiments were carried out to exclude nonspecific effects. RESULTS: Glibenclamide (KATP channel blocker) increased perfusion pressure to a maximum fetoplacental arterial pressure of 37 +/- 6 mm Hg in controls versus 15 +/- 6 mm Hg in diabetes (P < .05). 4-Aminopyridine (KV channel blocker) equally increased fetoplacental arterial pressure in controls, and in diabetes (21 +/- 4 mm Hg vs 22 +/- 2 mm Hg). Apamin and charybdotoxin (KCa channel blockers) caused a negligible rise in fetoplacental arterial pressure. CONCLUSION: In the fetoplacental circulation, KATP channels and KV channels significantly contribute to baseline vascular tone. In diabetes, vascular KATP channel function is impaired.

Contains fulltext : 48055.pdf (Publisher’s version ) (Open Access), PURPOSE: In malignant lymphoma, angiogenesis has been associated with adverse outcome or more aggressive clinical behavior. This correlation has been established in groups of patients with a large heterogeneity regarding lymphoma subtypes and treatment regimens. The aim of this study is to investigate the significance of vascularization in patients with follicular lymphoma receiving uniform first-line treatment. EXPERIMENTAL DESIGN: We assessed microvessel density (MVD) in pretreatment lymph node biopsies of 46 previously untreated patients with follicular lymphoma using anti-CD34 immunohistochemical staining and interactive quantification. In a selection of cases, vascular endothelial growth factor (VEGF)-RNA in situ hybridization was done. Patients were treated with cyclophosphamide-vincristine-prednisone induction chemotherapy combined with IFN-alpha2b. Thirty-six patients responded and received IFN-alpha as maintenance therapy. RESULTS: MVD ranged from 10 to 70 per measurement field of 0.19 mm2 (median, 38). Median progression-free survival was 47 months in patients with MVD in the highest tertile and only 13 months in patients with lower MVD. Overall survival in patients with low vessel density was 59 months. In patients with high vessel density, median overall survival was not reached. Multivariate analysis indicated that MVD was independently associated with overall survival. There was a lack of correlation between VEGF-RNA expression and vessel density. CONCLUSION: This study shows that in follicular lymphoma increased vascularization is associated with improved clinical outcome. Furthermore, VEGF-A expression seems not to be involved in follicular lymphoma angiogenesis.

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Contains fulltext : 47798.pdf (Publisher’s version ) (Open Access), OBJECT: Gliomas are the most common primary brain tumors, many of which (especially astrocytic and oligodendroglial neoplasms) are characterized by diffuse infiltrative growth in the preexisting brain tissue. Gliomatosis cerebri is a rare glial tumor and represents an extreme example of such diffuse infiltrative growth. This growth pattern not only hampers curative treatment but also allows for vessel cooptation rather than tumor angiogenesis as a way of vessel recruitment by the tumor tissue. The goal of this study was to establish the extent to which tumor angiogenesis occurs in gliomatosis cerebri. METHODS: Computerized image analysis was performed to assess quantitatively two microvascular parameters (vessel density and diameter) in different areas of a brain harboring a gliomatosis cerebri. These regions were the cerebral white and gray matter in which there was a diffuse infiltrative tumor, cerebral white and gray matter in which there was a more compact growth pattern of tumor cells, and normal cerebral white and gray matter. In addition, the authors performed immunohistochemical stainings for blood-brain barrier (BBB) characteristics (Glut-1 and PgP) on samples obtained in these different areas. The results of the quantitative analysis strongly indicated that in gliomatosis cerebri tumor, angiogenesis was completely absent, a finding that is corroborated by the fact that the microvasculature in gliomatosis cerebri persists in exhibiting immunohistochemical characteristics of the BBB. CONCLUSIONS: The results of this study may help resolve the difficulties in radiological detection and delineation of the diffuse infiltrative part of glial brain tumors and put the expectations for antiangiogenic treatment of such tumors into perspective.

Contains fulltext : 48590.pdf (Publisher’s version ) (Open Access), The objective of this study was to evaluate the histologic and immunohistopathologic effects of intratumorally given recombinant human interleukin-12 on the immune cells in the primary tumors and regional lymph nodes. Ten previously untreated patients with head and neck squamous cell carcinoma (HNSCC) were injected in the primary tumor twice to thrice, once weekly, at two dose levels of 100 or 300 ng/kg, before surgery. These patients were compared with 20 non-IL-12-treated control HNSCC patients. In the primary tumor, the number of CD56+ natural killer (NK) cells was increased in IL-12-treated patients compared with control patients. In some IL-12-treated patients, an impressive peritumoral invasion of CD20+ B cells was noticed. No differences were seen in the CD8+ or CD4+ T lymphocytes. Interestingly, major differences were apparent in the architecture of the enlarged lymph nodes of IL-12-treated patients; in particular, the distribution of B cells differed and fewer primary and secondary follicles with smaller germinal centers were observed. In addition, a decrease of dendritic cell lysosyme-associated membrane glycoprotein-positive cells in the paracortex was noted, resulting in a reduction of paracortical hyperplasia. In the lymph nodes, especially the CD56+ NK cells but also the CD8+ and CD4+ T lymphocytes, produced a high amount of IFN-gamma. Patients, irrespectively of IL-12 treatment, with a high number of CD56+ cells in the primary tumor had a better overall survival than those with a low number. In conclusion, after i.t. IL-12 treatment in HNSCC patients, the largest effect was seen on the NK cells, with a higher number in the primary tumor and a high IFN-gamma mRNA expression in the lymph nodes. Significant effects were noted on B cells, with altered lymph node architecture in every IL-12-treated patient and excessive peritumoral infiltration in some patients.

Contains fulltext : 57501.pdf (publisher's version ) (Closed access), The application of new surgical techniques in combination with preoperative radiotherapy has minimised the risk of local recurrence in rectal cancer. However, distant metastasis is still a serious problem after seemingly curative resection in patients with rectal cancer. The present study aimed to evaluate the methodology for quantification and the characteristics of the tumour vasculature in relation to the development of metastasis in patients with rectal cancer. From a large multicentre trial, 88 patients were selected, ensuring a relatively high percentage of metastasis. This selection facilitates the study of tumour vasculature characteristics in relation to metastasis. Vessel number, perimeter and area were assessed at both the invasive front and intratumoural area. Hot-spot and random selections were performed simultaneously. The median of each vessel parameter in the study population was used to separate patients into a low- and high-vessel group. Differences in development of distant metastasis were studied between low- and high-vessel groups. The data of the present study show that only vascular perimeter randomly assessed at the invasive front was associated with distant metastasis. Patients with a high score had a lower distant metastasis rate than patients with a low score (37% and 62%, respectively). High-vessel perimeter was independent of tumor node metastasis staging, but was associated with an increased presence of immune cells, comprising T cells, mast cells, eosinophils and neutrophils. This methodological study on the biological relevance of various vessel characteristics showed that a large vascular endothelial surface, as reflected by a high perimeter, was the only vessel characteristic indicative of improved patient outcome. The underlying principle for this association may be the improved immune response.

Contains fulltext : 57800.pdf (Publisher’s version ) (Open Access), OBJECTIVE: The goal of our study was to investigate the inverse correlation between number of genetic aberrations and malignancy grade in ependymal tumors at the ploidy level. METHODS: we examined seven myxopapillary ependymomas (mpEs) (WHO grade I), 28 spinal and cerebral ependymomas (Es) (WHO grade II), and 18 cerebral anaplastic ependymomas (aEs) (WHO grade III) using image DNA cytometry. The ploidy status was correlated with clinicopathological characteristics and with the results obtained by comparative genomic hybridization (CGH) analysis that we performed in about half of these tumors. RESULTS: mpEs were exclusively located in the spinal cord and aEs in the cerebrum only, whereas Es were located in both the spinal cord and brain. We found aneuploidy or tetraploidy to be common in the group of mpEs (6 out of 7) and much less frequent in Es (6 out of 28) and aEs (4 out of 18). Three-year postoperative survival was 100% for mpEs, 100% for spinal Es, 92% for cerebral Es, and 33% for aEs. Our CGH results in a selection of these tumors revealed the highest number of genetic aberrations in the mpEs (average 16; n = 2), a lower number in Es (average 12; n = 11) and the lowest number in aEs (average 5; n = 6). Interestingly, in the group of Es and aEs, a high number of genetic aberrations as detected by CGH was not correlated with aneuploidy or tetraploidy. Three patients, all with mpEs had local seeding. CONCLUSION: These results underline that mpEs are distinctly different from Es and aEs at the genetic level and that extensive genomic alterations and aneuploidy in ependymal tumors are not in itself an indicator of malignant behavior.

Contains fulltext : 144233.pdf (Publisher’s version ) (Open Access), Administration of a specific combination of anti-aminopeptidase A (APA) mAb (ASD-37/41) in mice induces an acute albuminuria which is independent of angiotensin II, a well-known substrate of APA. In the present experiments, we examined whether binding of the mAb initiated changes in the podocytic expression of cytoskeleton (-associated), adhesion and slit-diaphragm proteins in relation to the time course of albuminuria. In addition, we measured ultrastructurally the extent of foot process retraction (the number of foot processes per microm GBM) and the width of the slit pore between the podocytes by morphometric methods. An injection of the mAb combination ASD-37/41 induced a massive but transient albuminuria that started at 6 h, and peaked at 8 h, after which it declined. However, even at day 7 after injection of the mAbs some albuminuria was present. Injection of the combination ASD-3/41 or saline did not induce an albuminuria. Notably, we observed changes in the staining of CD2AP and podocin, two slit-pore-associated proteins that coincided with the start of the albuminuria. Nephrin staining was reduced and podocytic actin staining became more granular only at a time albuminuria was declining (24 h). The number of foot processes per microm GBM was already decreased at 4 h with a further reduction thereafter. The width of the slit pore was unchanged at the time of peak albuminuria and gradually decreased thereafter. At day 7, podocytic foot process effacement was even more prominent although albuminuria was only slightly abnormal. Expression of CD2AP was still granular. We observed however a change toward normal in the expression of podocin. Injection of saline or ASD-3/41 had no effect on the expression of podocytic proteins, the number of foot processes or width of the slit pore. Our data show that the onset of albuminuria in the anti-APA model is related to alterations in CD2AP and podocin, proteins that are important for maintaining slit-diaphragm structure an

Contains fulltext : 142800.pdf (Publisher’s version ) (Open Access), BACKGROUND: Quantification of microvessels in solid malignancies is regarded as a potential test to predict their clinicobiologic behavior. However, discordant results have been reported for head and neck cancer that may be explained by varying methods. METHODS: In this retrospective study, we therefore quantified the microvasculature in 20 nonmetastasized and 20 metastasized squamous cell carcinomas of the tongue, using recently developed methods. For immunohistochemical visualization of the vessels, we used anti-CD34 with a signal amplification step based on the catalyzed deposition of biotinylated tyramine. This protocol results in enhanced staining quality compared with standard protocols. For each tumor, a representative tissue section was systematically sampled with 40 to 60 standardized test fields. True color image analysis system was used to measure microvessel density (MVD) and to obtain additional information with regard to size categories of vessels. RESULTS: Remarkably, in the group of nonmetastasized tumors, the MVD was greater than in the metastasized tumors (p =.007). However, the microvessels with a diameter in the range of 10 to 15 microm predominated in the group of metastasized tongue carcinomas (p =.03). A logistic regression model based on the percentage of vessels smaller than 5 microm, classified 85% of patients with a metastasized tumor correctly and 75% of patients with a nonmetastasized tumor, independently of the clinical stage of the tumor. CONCLUSIONS: These results suggest that only vessels with a diameter larger than 10 microm, consistent with functional vessels, play a role in the process of metastasis. Further research more specifically into structural and functional characterization of blood and lymphatic vessels might help provide more insight into the relationship between microvasculature and the pathogenesis of metastasis in tongue carcinomas.

Contains fulltext : 144413.pdf (Publisher’s version ) (Open Access), BACKGROUND: Acquisition of DNA ploidy histograms by image analysis may yield important information regarding the behavior of premalignant cervical lesions. Accurate selection of nuclei for DNA measurement is an important prerequisite for obtaining reliable data. Traditionally, manual selection of nuclei of diagnostic and reference cells is performed by an experienced cytotechnologist. In the present study, a method for the fully automated identification of nuclei of diploid epithelial reference cells in Feulgen- restained Papanicolaou (PAP) smears is described. METHODS: The automated procedure consists of a decision tree implemented on the measurement device, containing nodes with feature threshold values and multivariate discriminant functions. Nodes were constructed to recognize debris and inflammatory cells, as well as diploid and nondiploid epithelial cells of the uterine cervix. Evaluation of the classifier was performed by comparing resulting diploid integrated optical densities with those from manually selected reference cells. RESULTS AND CONCLUSION: On average, automatically acquired values deviated 2.4% from manually acquired values, indicating that the method described in this paper may be useful in cytometric practice.

Contains fulltext : 144575.pdf (Publisher’s version ) (Open Access), BACKGROUND: After the menopause decreased concentrations of oestrogen may result in insufficient maturation of the vaginal epithelium, which can lead to a range of vaginal discomforts. This state of vaginal atrophy may be treated with oestrogen replacement treatment. Replens, a non-hormonal alternative to oestrogen replacement treatment has been shown to be effective in relieving symptoms related to vaginal atrophy in previous studies. AIMS: To study the effect of Replens on the maturation of the vaginal epithelium and morphology of the vaginal cells and to compare the results of a recently developed cytomorphometric method with manual assessment of the degree of maturation in vaginal smears. METHODS: Vaginal smears from 38 postmenopausal women suffering from symptoms related to vaginal atrophy were analysed manually and by cytomorphometry. The maturation value (MV) and the percentages of (para)basal, intermediate, and superficial cells (maturation index; MI) were measured by both methods before and after treatment with Replens. Cytomorphometry also measured mean cellular area, mean nuclear area, and mean area ratio. RESULTS: A correlation was shown between the two methods in the assessment of percentages of (para) basal and intermediate cells and MV. Cytomorphometric data showed a significant increase in mean cellular area, indicating a positive effect of Replens on the maturation of the vaginal epithelium. Changes in nuclear area and ratio between nuclear and cellular areas were not significant. Treatment with Replens did not influence MI or MV, as assessed by the two methods. CONCLUSIONS: Replens did have an effect on vaginal morphology. The automated procedure may be useful for the assessment of maturation in vaginal smears and is more sensitive to small (subvisual) changes.

KUN, 10 december 2001, Promotor : Ruiter, D.J., Item does not contain fulltext

Item does not contain fulltext, PURPOSE: The mechanisms that cause diabetes to impair the development of anastomotic strength in the intestine are poorly understood. We investigated whether short-term uncontrolled diabetes causes alterations in microscopic aspects of anastomoses from the ileum and colon. METHODS: Eighteen Wistar rats were rendered diabetic one week before operation by intravenous streptozotocin injection (50 mg/kg), resulting in nonfasting blood glucose levels of approximately 20 mmol/l. Another 18 age-matched rats were used as controls with a normal blood glucose range of 5 to 7 mmol/l. All rats underwent resection and anastomosis of both the ileum and colon. Animals were killed at one, three, or seven days after operation. Cellular and architectural parameters of anastomotic healing were scored in hematoxylin and eosin-stained sections. Anastomotic collagen content was analyzed by image analysis in picrosirius red-stained sections. RESULTS: Anastomotic necrosis, edema, and epithelial recovery were not affected by diabetes. In diabetic rats, the number of polymorphonuclear cells and macrophages was significantly (P = 0.025 and 0.0002, respectively) increased in ileal anastomoses one and three days after operation. In colonic anastomoses, the number of polymorphonuclear cells was increased at one (P = 0.001) and seven (P = 0.014) days after operation. Repair of the submucosal-muscular layer in colonic anastomoses from diabetic rats was impaired seven days after surgery (P = 0.0071), but in ileal anastomoses no difference was found. In the anastomotic area, collagen deposition at postoperative Days 1, 3, and 7 remained unaffected by diabetes. CONCLUSION: Experimental diabetes leads to alterations in cellular components involved in the early phase of repair of intestinal anastomoses but not to a reduced accumulation of wound collagen.

Contains fulltext : 144694.pdf (publisher's version ) (Open Access), The aims of this study of head and neck tissue samples were to develop an immunohistochemical protocol based on the catalysed reporter deposition (CARD) technique to enhance staining results for use in automated true colour image analysis, to assess the reproducibility of systematic tissue sampling in the angiogenic hot spot selection, and quantification of microvessel density (MVD) and other vessel characteristics. The latter data were compared between six metastasised tongue squamous cell carcinomas, vs. four non-metastasised. In comparison to the standard immunohistochemical protocol with anti-CD34 antibodies, CARD amplification resulted in both more intensely stained and larger numbers of vessels. Averaging the 10 most vascularised fields of the 40 to 60 systematically sampled fields in a tissue section resulted in an overall acceptable interobserver reproducibility for most assessed vessel parameters (r> or =0.76 and p< or =0.01). The percentage vessels with diameter <5 microm was significantly higher in the non-metastasised tongue carcinomas (p=0.02). However, for a number of tumours the effect of tissue sampling was significant.We conclude that CARD amplification is needed for reliable segmentation of vessels by image analysis systems, and that tumour heterogeneity is a limiting factor for all procedures in which tumour vascularity is assessed in a single tissue section.Figures on http://www.esacp.org/acp/2001/22-4/hannen.htm.

Contains fulltext : 144692.pdf (Publisher’s version ) (Open Access), Thus far, histopathological changes in the pancreatic islets of Zucker Diabetic Fatty (ZDF) rats, an animal model of type 2 diabetes mellitus (or non-insulin-dependent diabetes mellitus), have only been studied in male rats and in 18-weeks old rats or younger. In this study, we have examined in both male and female ZDF rats the histopathological changes longitudinally, from 6 to 32 weeks of age. We studied islet architecture and cellular distribution of the various islet hormones both in ZDF and control rats. In the ZDF rats, aging was initially associated with an enlargement of the islets. From 18 weeks onwards, no further enlargement was noted but islet boundaries became increasingly irregular, leading to the appearance of projections of endocrine cells into the surrounding exocrine tissue. At the islet boundaries as well as within the islets progressive fibrosis was observed with increasing amounts of collagen and reticular fibers. In the islets, staining intensity of both insulin and islet amyloid polypeptide (IAPP) increased slightly till 10 weeks of age and thereafter decreased rapidly. In contrast, the staining intensities of glucagon, somatostatin, and pancreatic polypeptide (PP) did not change. Even at the age of 32 weeks, just the beta-cells and not the other endocrine islet cells appear to be affected. In control rats, aging evoked only minor changes. Thus, we observed that during prolonged development of diabetes mellitus in both male and female ZDF rats histopathological changes in the pancreatic islets became progressively more severe, eventually leading to disintegration of the islets.

Contains fulltext : 122186.pdf (Publisher’s version ) (Open Access), OBJECTIVE: Increased microvessel density (MVD) of prostate cancer seems to be associated with poor prognosis and higher stage. Assessment of MVD using noninvasive methods could be of use in the work-up of patients with prostate cancer. The aim of the present study was to correlate three-dimensional contrast-enhanced power Doppler ultrasound (3D-CE-PDU) findings with MVD characteristics of radical prostatectomy specimens. METHODS: Seven patients with biopsy-proven prostate cancer had 3D-CE-PDU investigations 2-3 weeks after prostate biopsies were taken and prior to radical prostatectomy. The investigations were performed using Levovist contrast agent (Schering AG, Berlin, Germany) in combination with a Voluson 530D ultrasound scanner (Kretz AG, Zipf, Austria). The 7 patients were selected because of lateralization of the contrast enhancement. Histology slides were made of the side with 'contrast enhancement' and of the contralateral 'unenhanced' side and stained according to the catalyzed reporter deposition (CARD) amplification procedure, and MVD parameters were obtained. RESULTS: In all patients the MVD count of the 'enhanced' side was higher than the MVD count of the 'unenhanced' side, averaging 1.93 times higher. On histology all enhanced lesions proved to contain prostate cancer tissue (average maximum diameter 25 mm (range 17-31)). Two patients had a small bilateral tumor lesion (4 and 5 mm respectively) and in total 5 patients had even smaller satellite lesions (1-2 mm). The smaller lesions were not identified using 3D-CE-PDU. CONCLUSIONS: The present study shows that 3D power Doppler contrast ultrasonography is a minimally invasive imaging modality, which has the potential to visualize lesions with increased MVD. This property of 3D-CE-PDU could be used in the detection of prostate cancer.

Contains fulltext : 144700.pdf (publisher's version ) (Open Access), We have investigated the use of spectral imaging for multi-color analysis of permanent cytochemical dyes and enzyme precipitates on cytopathological specimens. Spectral imaging is based on Fourier-transform spectroscopy and digital imaging. A pixel-by-pixel spectrum-based color classification is presented of single-, double-, and triple-color in situ hybridization for centromeric probes in T24 bladder cancer cells, and immunocytochemical staining of nuclear antigens Ki-67 and TP53 in paraffin-embedded cervical brush material (AgarCyto). The results demonstrate that spectral imaging unambiguously identifies three chromogenic dyes in a single bright-field microscopic specimen. Serial microscopic fields from the same specimen can be analyzed using a spectral reference library. We conclude that spectral imaging of multi-color chromogenic dyes is a reliable and robust method for pixel color recognition and classification. Our data further indicate that the use of spectral imaging (a) may increase the number of parameters studied simultaneously in pathological diagnosis, (b) may provide quantitative data (such as positive labeling indices) more accurately, and (c) may solve segmentation problems currently faced in automated screening of cell- and tissue specimens.

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