G.J.L.H. Van Leenders

Three-dimensional contrast-enhanced power Doppler ultrasonography and conventional examination methods: the value of diagnostic predictors of prostate cancer.

Objective To investigate the value of three‐dimensional contrast‐enhanced power Doppler ultrasonography (3D‐CE‐PDU) in the diagnosis of prostate cancer and to compare 3D‐CE‐PDU with digital rectal examination (DRE), prostate‐specific antigen (PSA) levels, grey‐scale ultrasonography (GSU) and PDU.

The Application of Three–Dimensional Contrast–Enhanced Ultrasound to Measure Volume of Affected Tissue after HIFU Treatment for Localized Prostate Cancer

Introduction: Adequate monitoring of volume and location of affected tissue might provide helpful information when performing localized ablative therapy for prostate cancer. We hypothesize that the change in blood flow patterns after therapy in comparison to the blood flow pattern prior to therapy can be used to locate and quantify the amount of affected tissue due to the therapy. We describe the use of three–dimensional contrast–enhanced power Doppler ultrasound (3D–CE–PDU) to determine its additive value to visualize the extent of tissue defects created by high–intensity focused ultrasound (HIFU) in correlation with the histopathology of the prostatectomy specimen.Materials and Methods: Nine patients with biopsy–proven localized prostate cancer, who gave informed consent, were included in the protocol. HIFU treatment was performed 1 week in advance of radical retropubic prostatectomy (RRP) as part of a protocol to study the value of HIFU treatment as local ablative therapy for clinical T1–2N₀M₀ prostate carcinoma. 3D–CE–PDU was performed 1 day prior to unilateral HIFU treatment of the affected lobe on biopsy indication and 1 day before RRP using 2.5 g Levovist® (Schering AG, Germany) microbubble ultrasound contrast agent and a Kretz® Voluson 530D ultrasound scanner (Kretztechnik AG, Austria). Ultrasound data and pathology whole–mount sections were stored digitally to allow off–line processing. Human interpretations of HIFU measurements in three–dimensional ultrasound data were based on gray–scale information (local increase in gray level) in combination with power Doppler mode (absence of blood flow). Histopathological analysis of the whole–mount section revealed a broad band of hemorrhagic necrosis in the HIFU–treated area. Using both the ultrasound data and the pathology sections, the total volume of the prostate and of the HIFU–treated area was measured, and relative volumes were obtained.Results: Visual inspection of the three–dimensional reconstruction of contrast–enhanced Doppler measurements revealed the HIFU–affected prostate tissue by the absence of a blood flow pattern. Paired t tests of the relative HIFU volume indicated that Doppler results (mean 21.7%, SD ±10.8%) differed from the pathology results (mean 32.6%, SD ±16.0%), but a good correlation was found between the relative pathology HIFU volume (Pearson correlation r = 0.94, p<0.0015) and mean 3D–CE–PDU HIFU. Closer inspection of the pathology specimen revealed that the outer ring of the macroscopic hemorrhagic necrosis overestimated the actually dead tissue. On microscopy, the border of dead tissue appeared to be 1–2 mm inside the macroscopically identified red hemorrhagic band. 3D–CE–PDU HIFU volumes indicated by the single observers were not statistically different and correlated very well (Pearson correlation r = 0.98, p<0.001).Conclusion: The results illustrate that 3D–CE–PDU is a promising method to determine the size of the defect of HIFU ablative therapy for prostate carcinoma. The absence of blood flow indicated by three–dimensional power Doppler ultrasound images reflects affected tissue after HIFU treatment, and volume measurements of these areas can quantify the amount of affected tissue.

Stem cell differentiation within the human prostate epithelium: implications for prostate carcinogenesis.

The maintenance of human tissue integrity is governed by the proliferation of stem cells, identi®ed within rapidly proliferating organs like bone marrow, intestinal tract and squamous epithelium [1,2]. Stem cells are characterized by a relatively undifferentiated state and have a high proliferative capacity and a long life-span. After mitosis, they give rise to an intermediate cell population that modulates advanced tissue development by transient proliferation, while undergoing maturation towards a terminally differentiated state. Corresponding stem cell lineages have been proposed within the human prostate epithelium [3]. Within the human prostate epithelium, two cell types can be discriminated morphologically. High columnar luminal cells constitute the exocrine compartment of the prostate epithelium, secreting PSA and PAP into the glandular lumina. Luminal cells express high levels of the androgen receptor (AR) and are dependent on androgens for their survival. The basal cell compartment is believed to harbour stem cells of the entire prostate secretory epithelium. Basal cells express low/undetectable levels of AR and are independent of androgens for their survival [4]. By immunophenotypic characterization of the human prostate epithelium, researchers have identi®ed additional cell populations. First, neuroendocrine cells are dispersed within the prostate epithelium. Although the function of neuroendocrine cells is largely unknown, they might induce proliferation of adjacent cells modulated by paracrine secretion of neuropeptides like chromogranin A and synaptophysin [5]. A fourth distinct cell population is immunophenotypically characterized as an intermediate between basal and luminal cells. In 1989, Isaacs and Coffey [3] postulated a hierarchical stem cell model for the prostate epithelium. According to this model, stem cells of the entire prostate epithelium are localized within the basal cell compartment. By asymmetric cell division, they give rise to one stem cell copy (self-renewal) and one progenitor cell that is destined to amplify the development of the epithelium. After a limited number of cell cycles, a state of terminal differentiation is attained and cells will ®nally undergo apoptosis. During expansion, amplifying cells translocate towards the luminal cell layer and gain either exocrine or neuroendocrine characteristics. Interestingly, this stem-cell concept has gained increasing interest in the study of prostate carcinogenesis and is being considered in the development of novel treatments for prostate cancer. Prostate cancer is initially regarded as an androgen-dependent disease as therapeutic androgenablation induces massive apoptosis of malignant cells and clinically leads to tumour regression. However, after a remission period of up to several years, tumours usually progress despite low circulating androgen levels. Currently, no therapeutic options are available for the treatment of androgen-independent prostate cancer. In this study, differential immunophenotypic and cell biological characteristics of epithelial cell populations are analysed in relation to stem-cell models in the human prostate. Furthermore, we discuss the implications of epithelial cell differentiation for prostate carcinogenesis and tumour progression.

Guidelines on processing and reporting of prostate biopsies: the 2013 update of the pathology committee of the European Randomized Study of Screening for Prostate Cancer (ERSPC)

The histopathological examination of a prostate biopsy is the basis of prostate cancer diagnostics. Prostate cancer grade and extent of cancer in the diagnostic biopsy are important determinants of patient management. Quality of the prostate biopsy and its processing may influence the outcome of the histopathological evaluation. Further, an unambiguous and concise pathology reporting is essential for an appropriate clinical decision process. Since our initial report in 2003, there have been several practice changes, including the increased uptake of follow-up biopsies of patients who are under active surveillance, increasingly taken under guidance of MRI, or who underwent a prostate-sparing therapy. Therefore, we investigated the literature on the current pathology practices and recommendations with regard to prostate biopsy processing and reporting, both at initial diagnosis and in the context of follow-up biopsies in order to update our guidelines on the optimal processing and reporting of prostate biopsies.

Combined optical coherence tomography and intravascular ultrasound radio frequency data analysis for plaque characterization. Classification accuracy of human coronary plaques in vitro

This study was performed to characterize coronary plaque types by optical coherence tomography (OCT) and intravascular ultrasound (IVUS) radiofrequency (RF) data analysis, and to investigate the possibility of error reduction by combining these techniques. Intracoronary imaging methods have greatly enhanced the diagnostic capabilities for the detection of high-risk atherosclerotic plaques. IVUS RF data analysis and OCT are two techniques focusing on plaque morphology and composition. Regions of interest were selected and imaged with OCT and IVUS in 50 sections, from 14 human coronary arteries, sectioned post-mortem from 14 hearts of patients dying of non-cardiovascular causes. Plaques were classified based on IVUS RF data analysis (VH-IVUSTM), OCT and the combination of those. Histology was the benchmark. Imaging with both modalities and coregistered histology was successful in 36 sections. OCT correctly classified 24; VH-IVUS 25, and VH-IVUS/OCT combined, 27 out of 36 cross-sections. Systematic misclassifications in OCT were intimal thickening classified as fibroatheroma in 8 cross-sections. Misclassifications in VH-IVUS were mainly fibroatheroma as intimal thickening in 5 cross-sections. Typical image artifacts were found to affect the interpretation of OCT data, misclassifying intimal thickening as fibroatheroma or thin-cap fibroatheroma. Adding VH-IVUS to OCT reduced the error rate in this study.

Body mass index as a prognostic marker for biochemical recurrence in Dutch men treated with radical prostatectomy

To investigate whether body mass index (BMI) is a prognostic factor for biochemical recurrence (BCR) in Dutch men after radical prostatectomy (RP), as although epidemiological studies of obesity in relation to prostate cancer have provided conflicting results, recent studies from the USA suggest that a higher BMI is a risk factor for progression of prostate cancer.

Cushing’s syndrome due to ectopic ACTH production by (neuroendocrine) prostate carcinoma

Ectopic adrenocorticotropin (ACTH) secretion accounts for less than 10% of all causes of endogenous Cushing’s syndrome (CS) and is usually associated with neuroendocrine tumors and small cell carcinoma of the lung. We report the case of a 62-year-old man with CS due to ectopic ACTH production by small cell carcinoma of the prostate. He presented with severe hypercortisolism and associated symptoms. Plasma neuron specific enolase (NSE) was grossly elevated. Despite performing a laparoscopic bilateral adrenalectomy, the patient died as a result of sepsis with multi-organ failure. Post-mortem immunohistochemical staining of prostate tumor tissue showed ACTH expression. ACTH staining was also performed in four additional patients with small cell carcinoma of the urinary tract without CS. None of these additional cases showed a positive staining for ACTH. Although a rare cause of ectopic ACTH production, neuroendocrine prostate carcinoma should be considered in male patients with Cushing’s syndrome, in particular in those with an occult source of ACTH overproduction.

31 Cribriform groeipatroon in prostaatkanker met Gleason-score 7 is voorspellend voor metastase- en ziektespecifieke overleving

SamenvattingDe overleving van patiënten met prostaatkanker (PCa) met Gleason-score (GS) 7 bij radicale prostatectomie (RP) loopt uiteen.

30 Functionele capaciteit van nucleotideexcisie-repair correleert niet met verlaagde XPC-expressie in het urotheelcarcinoom van de blaas

SamenvattingDe DNA damage response (DDR) omvat verschillende mechanismen waarmee (kanker)cellen reageren op schade aan DNA veroorzaakt door chemo- of radiotherapie. Defecten in de DDR kunnen mogelijk de respons van kankercellen op antikankerbehandelingen voorspellen.