WorldWideScience

Sample records for prostate tissue predicts

  1. Magnetic resonance imaging and morphometric histologic analysis of prostate tissue composition in predicting the clinical outcome of terazosin therapy in benign prostatic hyperplasia

    Energy Technology Data Exchange (ETDEWEB)

    Isen, K. [Karaelmas Univ., Zonguldak (Turkey). School of Medicine; Sinik, Z.; Alkibay, T.; Sezer, C.; Soezen, S.; Atilla, S.; Ataoglu, O.; Isik, S.

    2001-02-01

    The purpose of this study was to determine whether magnetic resonance imaging (MRI) or quantitative color-imaged morphometric analysis (MA) of the prostate gland are related to the clinical response to terazosin. Thirty-six male patients with symptomatic benign prostatic hyperplasia (BPH) with a serum prostate-specific antigen level of 4-10 ng/mL underwent MRI with body coil, transrectal prostate unltrasonography and biopsy prior to terazosin therapy. For MRI-determined stromal and non-stromal BPH, the ratio of the signal intensity of the inner gland to the obturator internus muscle was evaluated. Histologic sections were stained with hematoxylin and eosin. The MA of the specimens was performed by Samba 2000. Results of the two techniques were interpreted according to the terazosin therapy results. The mean stromal percentage was 60.5{+-}18.0%. No statistically significant relationship was found between the clinical outcome of terazosin and the MRI findings. The MA results showed a significant relationship between the percentage of stroma and the percent change of the peak urinary flow rate, but not with the percent change of the international prostate symptom score after terazosin therapy (P<0.05). Magnetic resonance imaging alone is not sufficient in predicting the response to terazosin therapy. Morphometric analysis of BPH tissue composition can be used in predicting the clinical outcome of terazosin therapy but it is suitable only in patients for whom prostatic biopsy is necessary in order to rule out prostate cancer. (author)

  2. Magnetic resonance imaging and morphometric histologic analysis of prostate tissue composition in predicting the clinical outcome of terazosin therapy in benign prostatic hyperplasia

    International Nuclear Information System (INIS)

    Isen, K.; Sinik, Z.; Alkibay, T.; Sezer, C.; Soezen, S.; Atilla, S.; Ataoglu, O.; Isik, S.

    2001-01-01

    The purpose of this study was to determine whether magnetic resonance imaging (MRI) or quantitative color-imaged morphometric analysis (MA) of the prostate gland are related to the clinical response to terazosin. Thirty-six male patients with symptomatic benign prostatic hyperplasia (BPH) with a serum prostate-specific antigen level of 4-10 ng/mL underwent MRI with body coil, transrectal prostate unltrasonography and biopsy prior to terazosin therapy. For MRI-determined stromal and non-stromal BPH, the ratio of the signal intensity of the inner gland to the obturator internus muscle was evaluated. Histologic sections were stained with hematoxylin and eosin. The MA of the specimens was performed by Samba 2000. Results of the two techniques were interpreted according to the terazosin therapy results. The mean stromal percentage was 60.5±18.0%. No statistically significant relationship was found between the clinical outcome of terazosin and the MRI findings. The MA results showed a significant relationship between the percentage of stroma and the percent change of the peak urinary flow rate, but not with the percent change of the international prostate symptom score after terazosin therapy (P<0.05). Magnetic resonance imaging alone is not sufficient in predicting the response to terazosin therapy. Morphometric analysis of BPH tissue composition can be used in predicting the clinical outcome of terazosin therapy but it is suitable only in patients for whom prostatic biopsy is necessary in order to rule out prostate cancer. (author)

  3. A three-protein biomarker panel assessed in diagnostic tissue predicts death from prostate cancer for men with localized disease

    International Nuclear Information System (INIS)

    Severi, Gianluca; FitzGerald, Liesel M; Muller, David C; Pedersen, John; Longano, Anthony; Southey, Melissa C; Hopper, John L; English, Dallas R; Giles, Graham G; Mills, John

    2014-01-01

    Only a minority of prostate cancers lead to death. Because no tissue biomarkers of aggressiveness other than Gleason score are available at diagnosis, many nonlethal cancers are treated aggressively. We evaluated whether a panel of biomarkers, associated with a range of disease outcomes in previous studies, could predict death from prostate cancer for men with localized disease. Using a case-only design, subjects were identified from three Australian epidemiological studies. Men who had died of their disease, “cases” (N = 83), were matched to “referents” (N = 232), those who had not died of prostate cancer, using incidence density sampling. Diagnostic tissue was retrieved to assess expression of AZGP1, MUC1, NKX3.1, p53, and PTEN by semiquantitative immunohistochemistry (IHC). Poisson regression was used to estimate mortality rate ratios (MRRs) adjusted for age, Gleason score, and stage and to estimate survival probabilities. Expression of MUC1 and p53 was associated with increased mortality (MRR 2.51, 95% CI 1.14–5.54, P = 0.02 and 3.08, 95% CI 1.41–6.95, P = 0.005, respectively), whereas AZGP1 expression was associated with decreased mortality (MRR 0.44, 95% CI 0.20–0.96, P = 0.04). Analyzing all markers under a combined model indicated that the three markers were independent predictors of prostate cancer death and survival. For men with localized disease at diagnosis, assessment of AZGP1, MUC1, and p53 expression in diagnostic tissue by IHC could potentially improve estimates of risk of dying from prostate cancer based only on Gleason score and clinical stage

  4. The proportion of prostate biopsy tissue with Gleason pattern 4 or 5 predicts for biochemical and clinical outcome after radiotherapy for prostate cancer

    International Nuclear Information System (INIS)

    D'Ambrosio, David J.; Hanlon, Alexandra L.; Al-Saleem, Tahseen; Feigenberg, Steven J.; Horwitz, Eric M.; Uzzo, Robert G.; Pollack, Alan; Buyyounouski, Mark K.

    2007-01-01

    Purpose: To investigate the prognostic utility of the proportion of prostate biopsy tissue containing Gleason pattern 4 or 5 (GP4/5) after definitive radiotherapy (RT) for prostate cancer. Methods and Materials: A total of 568 patients with T1c-3 Nx/0 prostate cancer who received three-dimensional conformal RT alone between May 1989 and August 2001 were studied. There were 161 men with Gleason score 7-10 disease. The GP4/5 was defined as the percentage of biopsy tissue containing Gleason pattern 4 or 5. A Cox proportional hazards model was used for univariate and multivariate analyses (MVA) for biochemical failure (BF) (American Society of Therapeutic Radiology and Oncology definition) and distant metastasis (DM). A recursive partitioning analysis was done using the results of the MVA to identify a cutpoint for GP4/5. Results: The median follow-up was 46 (range, 13-114) months and median RT dose was 76 (range, 65-82) Gy. On MVA, increasing initial prostate-specific antigen (p = 0.0248) decreasing RT dose (continuous, p = 0.0022), T stage (T1/2 vs. T3) (p = 0.0136) and GP4/5 (continuous, p < 0.0001) were significant predictors of BF in a model also containing GS. GP4/5 was the only significant predictor of DM in the same model (p < 0.0001). Conclusion: The GP4/5 in prostate biopsy specimens is a predictor of BF and DM after RT independent of Gleason score. This parameter should be reported by the pathologist when reviewing prostatic biopsy specimens

  5. Stokes polarimetry imaging of dog prostate tissue

    Science.gov (United States)

    Kim, Jihoon; Johnston, William K., III; Walsh, Joseph T., Jr.

    2010-02-01

    Prostate cancer is the second leading cause of death in the United States in 2009. Radical prostatectomy (complete removal of the prostate) is the most common treatment for prostate cancer, however, differentiating prostate tissue from adjacent bladder, nerves, and muscle is difficult. Improved visualization could improve oncologic outcomes and decrease damage to adjacent nerves and muscle important for preservation of potency and continence. A novel Stokes polarimetry imaging (SPI) system was developed and evaluated using a dog prostate specimen in order to examine the feasibility of the system to differentiate prostate from bladder. The degree of linear polarization (DOLP) image maps from linearly polarized light illumination at different visible wavelengths (475, 510, and 650 nm) were constructed. The SPI system used the polarization property of the prostate tissue. The DOLP images allowed advanced differentiation by distinguishing glandular tissue of prostate from the muscular-stromal tissue in the bladder. The DOLP image at 650 nm effectively differentiated prostate and bladder by strong DOLP in bladder. SPI system has the potential to improve surgical outcomes in open or robotic-assisted laparoscopic removal of the prostate. Further in vivo testing is warranted.

  6. Nd : YAG surgical laser effects in canine prostate tissue: temperature and damage distribution

    NARCIS (Netherlands)

    van Nimwegen, S. A.; L'Eplattenier, H. F.; Rem, A. I.; van der Lugt, J. J.; Kirpensteijn, J.

    2009-01-01

    An in vitro model was used to predict short-term, laser-induced, thermal damage in canine prostate tissue. Canine prostate tissue samples were equipped with thermocouple probes to measure tissue temperature at 3, 6, 9 and 12 mm depths. The tissue surface was irradiated with a Nd:YAG laser in contact

  7. Prostate tissue metal levels and prostate cancer recurrence in smokers.

    Science.gov (United States)

    Neslund-Dudas, Christine; Kandegedara, Ashoka; Kryvenko, Oleksandr N; Gupta, Nilesh; Rogers, Craig; Rybicki, Benjamin A; Dou, Q Ping; Mitra, Bharati

    2014-02-01

    Although smoking is not associated with prostate cancer risk overall, smoking is associated with prostate cancer recurrence and mortality. Increased cadmium (Cd) exposure from smoking may play a role in progression of the disease. In this study, inductively coupled plasma mass spectrometry was used to determine Cd, arsenic (As), lead (Pb), and zinc (Zn) levels in formalin-fixed paraffin embedded tumor and tumor-adjacent non-neoplastic tissue of never- and ever-smokers with prostate cancer. In smokers, metal levels were also evaluated with regard to biochemical and distant recurrence of disease. Smokers (N = 25) had significantly higher Cd (median ppb, p = 0.03) and lower Zn (p = 0.002) in non-neoplastic tissue than never-smokers (N = 21). Metal levels were not significantly different in tumor tissue of smokers and non-smokers. Among smokers, Cd level did not differ by recurrence status. However, the ratio of Cd ppb to Pb ppb was significantly higher in both tumor and adjacent tissue of cases with distant recurrence when compared with cases without distant recurrence (tumor tissue Cd/Pb, 6.36 vs. 1.19, p = 0.009, adjacent non-neoplastic tissue Cd/Pb, 6.36 vs. 1.02, p = 0.038). Tissue Zn levels were also higher in smokers with distant recurrence (tumor, p = 0.039 and adjacent non-neoplastic, p = 0.028). These initial findings suggest that prostate tissue metal levels may differ in smokers with and without recurrence. If these findings are confirmed in larger studies, additional work will be needed to determine whether variations in metal levels are drivers of disease progression or are simply passengers of the disease process.

  8. Radioimmunoassay of tissue steroids in adenocarcinoma of the prostate

    International Nuclear Information System (INIS)

    Belis, J.A.; Tarry, W.F.

    1981-01-01

    Tissue steroid levels in 48 needle-biopsy samples of adenocarcinoma of the prostate were quantified by radioimmunoassay (RIA). Tissue levels of dihydrotestosterone (DHT), estradiol-17β, and estrone were correlated with tumor stage, histologic grade, and patient response to endocrine therapy. All patients with well-differentiated carcinoma of the prostate had tissue DHT content greater than 2.0 ng/g while 35% of patients with moderately differentiated or poorly differentiated tumors had tissue DHT content less than 2.0 ng/g. DHT content appeared to be unrelated to tumor stage. Estradiol and estrone content correlated well with tumor grade but not with tumor stage. DHT levels were measured in 17 patients with symptomatic Stage D 2 carcinoma of the prostate. Thirteen patients with DHT content greater than 2.0 ng/g initially had an objective and/or subjective response to endocrine therapy. Four patients with tissue DHT levels below 2.0 ng/g had no response to hormonal therapy. Quantification of tissue DHT content by RIA is a promising method for predicting initial response to hormonal therapy in adenocarcinoma of the prostate

  9. Tissue concentrations of prostate-specific antigen in prostatic carcinoma and benign prostatic hyperplasia.

    Science.gov (United States)

    Pretlow, T G; Pretlow, T P; Yang, B; Kaetzel, C S; Delmoro, C M; Kamis, S M; Bodner, D R; Kursh, E; Resnick, M I; Bradley, E L

    1991-11-11

    Prostate-specific antigen (PSA), as measured in peripheral blood, is currently the most widely used marker for the assessment of tumor burden in the longitudinal study of patients with carcinoma of the prostate (PCA). Studies from other laboratories have led to the conclusion that a given volume of PCA causes a much higher level of PSA in the peripheral circulation of patients than a similar volume of prostate without carcinoma. We have evaluated PSA in the resected tissues immunohistochemically and in extracts of PCA and of prostates resected because of benign prostatic hyperplasia (BPH) with an enzyme-linked immunosorbent assay. Immunohistochemical results were less quantitative than but consistent with the results of the ELISA of tissue extracts. Immunohistochemically, there was considerable heterogeneity in the expression of PSA by both PCA and BPH both within and among prostatic tissues from different patients. While the levels of expression of PSA in these tissues overlap broadly, PSA is expressed at a lower level in PCA than in BPH when PSA is expressed as a function of wet weight of tissue (p = 0.0095), wet weight of tissue/% epithelium (p less than 0.0001), protein extracted from the tissue (p = 0.0039), or protein extracted/% epithelium (p less than 0.0001).

  10. Characterization of adenoviral transduction profile in prostate cancer cells and normal prostate tissue.

    Science.gov (United States)

    Ai, Jianzhong; Tai, Phillip W L; Lu, Yi; Li, Jia; Ma, Hong; Su, Qin; Wei, Qiang; Li, Hong; Gao, Guangping

    2017-09-01

    Prostate diseases are common in males worldwide with high morbidity. Gene therapy is an attractive therapeutic strategy for prostate diseases, however, it is currently underdeveloped. As well known, adeno virus (Ad) is the most widely used gene therapy vector. The aims of this study are to explore transduction efficiency of Ad in prostate cancer cells and normal prostate tissue, thus further providing guidance for future prostate pathophysiological studies and therapeutic development of prostate diseases. We produced Ad expressing enhanced green fluorescence protein (EGFP), and characterized the transduction efficiency of Ad in both human and mouse prostate cancer cell lines in vitro, as well as prostate tumor xenograft, and wild-type mouse prostate tissue in vivo. Ad transduction efficiency was determined by EGFP fluorescence using microscopy and flow cytometry. Cell type-specific transduction was examined by immunofluorescence staining of cell markers. Our data showed that Ad efficiently transduced human and mouse prostate cancer cells in vitro in a dose dependent manner. Following intratumoral and intraprostate injection, Ad could efficiently transduce prostate tumor xenograft and the major prostatic cell types in vivo, respectively. Our findings suggest that Ad can efficiently transduce prostate tumor cells in vitro as well as xenograft and normal prostate tissue in vivo, and further indicate that Ad could be a potentially powerful toolbox for future gene therapy of prostate diseases. © 2017 Wiley Periodicals, Inc.

  11. Androgen receptor profiling predicts prostate cancer outcome

    NARCIS (Netherlands)

    S. Stelloo (Suzan); E. Nevedomskaya (Ekaterina); H.G. van der Poel (Henk G.); J. de Jong (Jeroen); G.J.H.L. Leenders (Geert); G.W. Jenster (Guido); L. Wessels (Lodewyk); A.M. Bergman (Andries); W. Zwart (Wilbert)

    2015-01-01

    textabstractProstate cancer is the second most prevalent malignancy in men. Biomarkers for outcome prediction are urgently needed, so that high-risk patients could be monitored more closely postoperatively. To identify prognostic markers and to determine causal players in prostate cancer

  12. TISSUE POLYPEPTIDE-SPECIFIC ANTIGEN - A DISCRIMINATIVE PARAMETER BETWEEN PROSTATE-CANCER AND BENIGN PROSTATIC HYPERTROPHY

    NARCIS (Netherlands)

    MARRINK, J; OOSTEROM, R; BONFRER, HMG; SCHRODER, FH; MENSINK, HJA

    1993-01-01

    The serum concentration of the cell proliferation marker TPS (tissue polypeptide-specific antigen) was compared with the tumour marker PSA (prostate specific antigen). PSA was found elevated in 50% of the benign prostatic hypertrophy (BPH) patients, in 88% of the patients with active prostate cancer

  13. [Role of angiotensin II receptor type 2 in predicting biochemical recurrence in the treatment of prostate cancer].

    Science.gov (United States)

    Chibichyan, M B; Kogan, M I; Chernogubova, E A; Pavlenko, I A; Matishov, D G

    2016-12-01

    To identify markers for predicting aggressive forms of prostate cancer. The study retrospectively evaluated expression of angiotensin II type 2 receptors (AT2-R) in prostate needle biopsy tissue from patients with and without biochemical recurrence after combined hormone and radiation therapy. The study findings showed that low expression of AT2-R in prostate tissue was associated with a high risk of biochemical recurrence. The data on the nature of AT2-R expression in prostate tissue of prostate cancer patients may be considered as a tool for predicting biochemical recurrence after combined hormone and radiation therapy. The test has a sensitivity of 87.5% and specificity of 85.71%.

  14. Predictive value of prostate-specific antigen for prostate cancer

    DEFF Research Database (Denmark)

    Shepherd, Leah; Borges, Alvaro Humberto; Ravn, Lene

    2014-01-01

    INTRODUCTION: Although prostate cancer (PCa) incidence is lower in HIV+ men than in HIV- men, the usefulness of prostate-specific antigen (PSA) screening in this population is not well defined and may have higher false negative rates than in HIV- men. We aimed to describe the kinetics and predict......INTRODUCTION: Although prostate cancer (PCa) incidence is lower in HIV+ men than in HIV- men, the usefulness of prostate-specific antigen (PSA) screening in this population is not well defined and may have higher false negative rates than in HIV- men. We aimed to describe the kinetics...... and predictive value of PSA in HIV+ men. METHODS: Men with PCa (n=21) and up to two matched controls (n=40) with prospectively stored plasma samples before PCa (or matched date in controls) were selected. Cases and controls were matched on date of first and last sample, age, region of residence and CD4 count...... at first sample date. Total PSA (tPSA), free PSA (fPSA), testosterone and sex hormone binding globulin (SHBG) were measured. Conditional logistic regression models investigated associations between markers and PCa. Sensitivity and specificity of using tPSA >4 µg/L to predict PCa was calculated. Mixed...

  15. Early prostate cancer antigen expression in predicting presence of prostate cancer in men with histologically negative biopsies.

    Science.gov (United States)

    Hansel, D E; DeMarzo, A M; Platz, E A; Jadallah, S; Hicks, J; Epstein, J I; Partin, A W; Netto, G J

    2007-05-01

    Early prostate cancer antigen is a nuclear matrix protein that was recently shown to be expressed in prostate adenocarcinoma and adjacent benign tissue. Previous studies have demonstrated early prostate cancer antigen expression in benign prostate tissue up to 5 years before a diagnosis of prostate carcinoma, suggesting that early prostate cancer antigen could be used as a potential predictive marker. We evaluated early prostate cancer antigen expression by immunohistochemistry using a polyclonal antibody (Onconome Inc., Seattle, Washington) on benign biopsies from 98 patients. Biopsies were obtained from 4 groups that included 39 patients with first time negative biopsy (group 1), 24 patients with persistently negative biopsies (group 2), 8 patients with initially negative biopsies who were subsequently diagnosed with prostate carcinoma (group 3) and negative biopsies obtained from 27 cases where other concurrent biopsies contained prostate carcinoma (group 4). Early prostate cancer antigen staining was assessed by 2 of the authors who were blind to the group of the examined sections. Staining intensity (range 0 to 3) and extent (range 1 to 3) scores were assigned. The presence of intensity 3 staining in any of the blocks of a biopsy specimen was considered as positive for early prostate cancer antigen for the primary outcome in the statistical analysis. In addition, as secondary outcomes we evaluated the data using the proportion of blocks with intensity 3 early prostate cancer antigen staining, the mean of the product of staining intensity and staining extent of all blocks within a biopsy, and the mean of the product of intensity 3 staining and extent. Primary outcome analysis revealed the proportion of early prostate cancer antigen positivity to be highest in group 3 (6 of 8, 75%) and lowest in group 2 (7 of 24, 29%, p=0.04 for differences among groups). A relatively higher than expected proportion of early prostate cancer antigen positivity was present in

  16. Prostate Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing prostate cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  17. Prostatic Tissue Elimination After Prostatic Artery Embolization (PAE): A Report of Three Cases

    Energy Technology Data Exchange (ETDEWEB)

    Leite, Leandro Cardarelli; Assis, Andre Moreira de; Moreira, Airton Mota [University of Sao Paulo, Department of Radiology (Brazil); Harward, Sardis Honoria [The Dartmouth Institute for Health Policy and Clinical Practice (United States); Antunes, Alberto Azoubel [University of Sao Paulo, Discipline of Urology (Brazil); Carnevale, Francisco Cesar, E-mail: francisco.carnevale@criep.com.br [University of Sao Paulo, Department of Radiology (Brazil)

    2017-06-15

    PurposeWe report three cases of spontaneous prostatic tissue elimination through the urethra while voiding following technically successful prostatic artery embolization (PAE) as a treatment for lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH).MethodsAll patients were embolized with 100- to 300-μm microspheres alone or in combination with 300- to 500-μm microspheres.ResultsDuring follow-up prior to eliminating the tissue fragments, the three patients all presented with intermittent periods of LUTS improvement and aggravation. After expelling the prostatic tissue between 1 and 5 months of follow-up, significant improvements in LUTS and urodynamic parameters were observed in all patients.ConclusionsUrethral obstruction after PAE caused by sloughing prostate tissue is a potential complication of the procedure and should be considered in patients with recurrent LUTS in order to avoid inappropriate management.

  18. Sexual steroids in serum and prostatic tissue of human non-cancerous prostate (STERPROSER trial).

    Science.gov (United States)

    Neuzillet, Yann; Raynaud, Jean-Pierre; Radulescu, Camélia; Fiet, Jean; Giton, Franck; Dreyfus, Jean-François; Ghoneim, Tarek P; Lebret, Thierry; Botto, Henry

    2017-11-01

    The specific involvement of the sex steroids in the growth of the prostatic tissue remains unclear. Sex steroid concentrations in plasma and in fresh surgical samples of benign central prostate were correlated to prostate volume. Monocentric prospective study performed between September 2014 and January 2017. Age, obesity parameters, and both serum and intraprostatic concentrations of sex steroids were collected complying with the latest Endocrine Society guidelines and the steroids assessed by GC/MS. Statistical calculations were adjusted for age and body mass index (BMI). Thirty-two patients, equally divided between normal- and high-volume prostate groups, were included in the analysis. High-volume prostate patients were older, heavier and had higher BMI. Comparison adjusted for age and BMI showed higher DHT concentrations in high-volume prostate. Both normal- and high-volume prostate tissues concentrate sex steroids in a similar way. Comparison of enzymatic activity surrogate marker ratios within tissue highlighted similar TT/E1 and TT/E2 ratios, and higher DHT/E1 ratio and lower DHT/PSA ratio in the high-volume prostates. STERPROSER trial provides evidence for higher DHT concentration in highvolume prostates, that could reflect either higher 5-alpha reductase expression or lower expression of downstream metabolizing enzymes such as 3a-hydoxysteroid dehydrogenase. © 2017 Wiley Periodicals, Inc.

  19. Prostate-Specific Antigen Mass and Free Prostate-Specific Antigen Mass for Predicting the Prostate Volume of Korean Men With Biopsy-Proven Benign Prostatic Hyperplasia

    OpenAIRE

    Park, Tae Yong; Chae, Ji Yun; Kim, Jong Wook; Kim, Jin Wook; Oh, Mi Mi; Yoon, Cheol Yong; Moon, Du Geon

    2013-01-01

    Purpose It has been reported that prostate-specific antigen (PSA) correlates with prostate volume. Recently, some studies have reported that PSA mass (PSA adjusted for plasma volume) is more accurate than PSA at predicting prostate volume. In this study, we analyzed the accuracy of PSA and the related parameters of PSA mass, free PSA (fPSA), and fPSA mass in predicting prostate volume. Materials and Methods We retrospectively investigated 658 patients who underwent prostate biopsy from 2006 t...

  20. Prostate-specific antigen velocity is not better than total prostate-specific antigen in predicting prostate biopsy diagnosis.

    Science.gov (United States)

    Gorday, William; Sadrzadeh, Hossein; de Koning, Lawrence; Naugler, Christopher T

    2015-12-01

    1.) Identify whether prostate-specific antigen velocity improves the ability to predict prostate biopsy diagnosis. 2.) Test whether there is an increase in the predictive capability of models when Gleason 7 prostate cancers are separated into a 3+4 and a 4+3 group. Calgary Laboratory Services' Clinical Laboratory Information System was searched for prostate biopsies reported between January 1, 2009 and December 31, 2013. Total prostate-specific antigen tests were recorded for each patient from January 1, 2007 to the most recent test before their recorded prostate biopsy. The data set was divided into the following three groups for comparison; benign, all prostate cancer and Gleason 7-10. The Gleason grade 7-10 group was further divided into 4+3 and 3+4 Gleason 7 prostate cancers. Prostate-specific antigen velocity was calculated using four different methods found in the literature. Receiver operator curves were used to assess operational characteristics of the tests. 4622 men between the ages of 40-89 with a prostate biopsy were included for analysis. Combining prostate-specific antigen velocity with total prostate-specific antigen (AUC=0.570-0.712) resulted in small non-statistically significant changes to the area under the curve compared to the area under the curve of total prostate-specific antigen alone (AUC=0.572-0.699). There were marked increases in the area under curves when 3+4 and 4+3 Gleason 7 cancers were separated. Prostate-specific antigen velocity does not add predictive value for prostate biopsy diagnosis. The clinical significance of the prostate specific antigen test can be improved by separating Gleason 7 prostate cancers into a 3+4 and 4+3 group. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  1. Hypoxic Prostate/Muscle PO2 Ratio Predicts for Outcome in Patients With Localized Prostate Cancer: Long-Term Results

    International Nuclear Information System (INIS)

    Turaka, Aruna; Buyyounouski, Mark K.; Hanlon, Alexandra L.; Horwitz, Eric M.; Greenberg, Richard E.; Movsas, Benjamin

    2012-01-01

    Purpose: To correlate tumor oxygenation status with long-term biochemical outcome after prostate brachytherapy. Methods and Materials: Custom-made Eppendorf PO 2 microelectrodes were used to obtain PO 2 measurements from the prostate (P), focused on positive biopsy locations, and normal muscle tissue (M), as a control. A total of 11,516 measurements were obtained in 57 men with localized prostate cancer immediately before prostate brachytherapy was given. The Eppendorf histograms provided the median PO 2 , mean PO 2 , and % 2 ratio on BF. Results: With a median follow-up time of 8 years, 12 men had ASTRO BF and 8 had Phoenix BF. On multivariate analysis, P/M PO 2 ratio 2 ratio 2 ratio) significantly predicts for poor long-term biochemical outcome, suggesting that novel hypoxic strategies should be investigated.

  2. Can Prostate-Specific Antigen Kinetics before Prostate Biopsy Predict the Malignant Potential of Prostate Cancer?

    Science.gov (United States)

    Kim, Sang Jin; Jeong, Tae Yoong; Yoo, Dae Seon; Park, Jinsung; Cho, Seok; Kang, Seok Ho; Lee, Sang Hyub; Jeon, Seung Hyun; Lee, Tchun Yong; Park, Sung Yul

    2015-11-01

    To predict the malignant potential of prostate cancer (PCa) according to prostate-specific antigen velocity (PSAV), PSA density (PSAD), free/total PSA ratio (%fPSA), and digital rectal examination (DRE). From January 2009 to December 2012, 548 adult male patients were diagnosed with PCa by prostate biopsy at four hospitals in Korea. We retrospectively analyzed 155 adult male patients with an initial PSA level≤10 ng/mL and whose PSA levels had been checked more than two times at least 6 months before they had been diagnosed with PCa, with test intervals of more than 3 months. Patients with a urinary tract infection, and patients who had previously undergone cystoscopy or surgery of the prostate were excluded. We separated patients into two groups according to Gleason sum [Gleason sum≤7 (n=134) or Gleason sum≥8 (n=21)] and the presence of extracapsular invasion [organ confined (n=129) or extracapsular invasion (n=26)]. Differences between the groups were compared. The group with a Gleason sum≥8 or extracapsular invasion of PCa showed high PSAV and significantly lower %fPSA. There were no significant differences in PSAD and the presence of an abnormality on DRE between two groups. In PCa patients treated with other therapies besides prostatectomy, a high PSA velocity and a low %fPSA may predict high grade PCa with a Gleason sum≥8 or the presence of extracapsular invasion.

  3. [Prostate cancer detection by assessing stiffness of different tissues using shear wave ultrasound elastog- raphy].

    Science.gov (United States)

    Glybochko, P V; Alyaev, Yu G; Amosov, A V; Krupinov, G E; Ganzha, T M; Vorobev, A V; Lumpov, I S; Semendyaev, R I

    2016-08-01

    patients of groups 1 and 2. Threshold values of stiffness (Emean) were determined, which normally range from 0 to 23 kPa, from 23.4 to 50 kPa in prostatic hyperplasia and 50.5 kPa and greater in prostate cancer. A total of 220 patients in groups 1 and 2 were found to have prostate cancer. The findings showed increased stiffness of prostate tissue depending on tumor differentiation, Gleason score, and hence, cancer risk. The sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) were calculated for SWUE, biopsy based on 6 peripheral points used during SWUE, and for histologic findings from prostate cross sections. When compared to needle biopsy, Se, Sp, PPV, NPV for SWUE were 90.8, 94.6, 56.6 and 97.9%, respectively. The study findings suggest a high diagnostic performance of SWUE in detecting prostate cancer.

  4. Prostate Cancer Probability Prediction By Machine Learning Technique.

    Science.gov (United States)

    Jović, Srđan; Miljković, Milica; Ivanović, Miljan; Šaranović, Milena; Arsić, Milena

    2017-11-26

    The main goal of the study was to explore possibility of prostate cancer prediction by machine learning techniques. In order to improve the survival probability of the prostate cancer patients it is essential to make suitable prediction models of the prostate cancer. If one make relevant prediction of the prostate cancer it is easy to create suitable treatment based on the prediction results. Machine learning techniques are the most common techniques for the creation of the predictive models. Therefore in this study several machine techniques were applied and compared. The obtained results were analyzed and discussed. It was concluded that the machine learning techniques could be used for the relevant prediction of prostate cancer.

  5. Prostate cancer outcome and tissue levels of metal ions

    Science.gov (United States)

    Sarafanov, A.G.; Todorov, T.I.; Centeno, J.A.; MacIas, V.; Gao, W.; Liang, W.-M.; Beam, C.; Gray, Marion A.; Kajdacsy-Balla, A.

    2011-01-01

    BACKGROUNDThere are several studies examining prostate cancer and exposure to cadmium, iron, selenium, and zinc. Less data are available on the possible influence of these metal ions on prostate cancer outcome. This study measured levels of these ions in prostatectomy samples in order to examine possible associations between metal concentrations and disease outcome.METHODSWe obtained formalin fixed paraffin embedded tissue blocks of prostatectomy samples of 40 patients with PSA recurrence, matched 1:1 (for year of surgery, race, age, Gleason grading, and pathology TNM classification) with tissue blocks from 40 patients without recurrence (n = 80). Case–control pairs were compared for the levels of metals in areas adjacent to tumors. Inductively coupled plasma-mass spectrometry (ICP-MS) was used for quantification of Cd, Fe, Zn, and Se.RESULTSPatients with biochemical (PSA) recurrence of disease had 12% lower median iron (95 µg/g vs. 111 µg/g; P = 0.04) and 21% lower zinc (279 µg/g vs. 346 µg/g; P = 0.04) concentrations in the normal-appearing tissue immediately adjacent to cancer areas. Differences in cadmium (0.489 µg/g vs. 0.439 µg/g; 4% higher) and selenium (1.68 µg/g vs. 1.58 µg/g; 5% higher) levels were not statistically significant in recurrence cases, when compared to non-recurrences (P = 0.40 and 0.21, respectively).CONCLUSIONSThere is an association between low zinc and low iron prostate tissue levels and biochemical recurrence in prostate cancer. Whether these novel findings are a cause or effect of more aggressive tumors, or whether low zinc and iron prostatic levels raise implications for therapy, remains to be investigated. 

  6. Does Small Prostate Predict High Grade Prostate Cancer?

    International Nuclear Information System (INIS)

    Caliskan, S.; Kaba, S.; Koca, O.; Ozturk, M. I.

    2017-01-01

    Objective: The current study is aimed to assess the patients who underwent radical prostatectomy for prostate cancer and investigate the association between prostate size and adverse outcomes at final pathology. Study Design: Comparative, descriptive study. Place and Duration of Study: Haydarpasa Numune Training and Research Hospital, Turkey, from January 2008 to January 2016. Methodology: The patients treated with open radical prostatectomy for prostate cancer were reviewed. Patient characteristics including prostate specific antigen (PSA), free PSA levels, age, biopsy, and radical prostatectomy results were recorded. The patients whose data were complete or prostate weight was equal to or less than 80 gm, were included in the study. Patients with < 40 gm prostate weight was in group 1 and the patients in group 2 had a prostate weight from 40 to 80 gm. High grade prostate cancer was defined to have a Gleason score between 7 or higher at biopsy and final pathology. Pathology and biopsy results were compared within groups. MedCalc Statistical Software demo version was used for statistical analyses. Results: There were 162 patients in this study. Of these, 71 (43.82 percent) patients were in group 1 and 91 (56.17 percent) patients were in group 2. The age ranged from 49 to 76 years. Mean value of 62.70 +-6.82 and 65.82 +- 5.66 years in group 1 and 2, respectively. Fifty (70.42 percent) and 68 patients (74.74 percent) had a Gleason score of 6 in group 1 and 2, respectively. Organconfined disease was reported in 53 patients (74.64 percent) in group 1 and in 78 patients (85.71 percent) in group 2. Gleason score concordance between biopsy and prostatectomy was reported in 61 patients (67.03 percent) and downgrading was detected in 4 patients (4.4 percent) in group 2. The median tumor volume of the patients was 4.47 cm/sup 3/ in group 1 and 6 cm/sup 3/ in group 2 (p=0.502). High grade prostate cancer was reported in 52.11 percent and 45.05 percent of the patients in

  7. Prostate Health Index improves multivariable risk prediction of aggressive prostate cancer.

    Science.gov (United States)

    Loeb, Stacy; Shin, Sanghyuk S; Broyles, Dennis L; Wei, John T; Sanda, Martin; Klee, George; Partin, Alan W; Sokoll, Lori; Chan, Daniel W; Bangma, Chris H; van Schaik, Ron H N; Slawin, Kevin M; Marks, Leonard S; Catalona, William J

    2017-07-01

    To examine the use of the Prostate Health Index (PHI) as a continuous variable in multivariable risk assessment for aggressive prostate cancer in a large multicentre US study. The study population included 728 men, with prostate-specific antigen (PSA) levels of 2-10 ng/mL and a negative digital rectal examination, enrolled in a prospective, multi-site early detection trial. The primary endpoint was aggressive prostate cancer, defined as biopsy Gleason score ≥7. First, we evaluated whether the addition of PHI improves the performance of currently available risk calculators (the Prostate Cancer Prevention Trial [PCPT] and European Randomised Study of Screening for Prostate Cancer [ERSPC] risk calculators). We also designed and internally validated a new PHI-based multivariable predictive model, and created a nomogram. Of 728 men undergoing biopsy, 118 (16.2%) had aggressive prostate cancer. The PHI predicted the risk of aggressive prostate cancer across the spectrum of values. Adding PHI significantly improved the predictive accuracy of the PCPT and ERSPC risk calculators for aggressive disease. A new model was created using age, previous biopsy, prostate volume, PSA and PHI, with an area under the curve of 0.746. The bootstrap-corrected model showed good calibration with observed risk for aggressive prostate cancer and had net benefit on decision-curve analysis. Using PHI as part of multivariable risk assessment leads to a significant improvement in the detection of aggressive prostate cancer, potentially reducing harms from unnecessary prostate biopsy and overdiagnosis. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

  8. Role of Transition Zone Index in the Prediction of Clinical Benign Prostatic Hyperplasia

    Directory of Open Access Journals (Sweden)

    Muhammet Güzelsoy

    2016-12-01

    Full Text Available Objective The objective of this study was to determine the role of the transition zone (TZ index (TZI in the prediction of clinical benign prostatic hyperplasia (BPH in patients who underwent transurethral prostatectomy (TUR-P and to analyze the correlation between the amount of resected tissue and TZ volume (TZV. Materials and Methods Twenty-six male clinical BPH patients with obstructive complaints and 17 male benign prostate enlargement (BPE patients without any complaints were included in the study. Both the groups were over the age of 50. Clinical BPH patients underwent complete TUR-P. Statistical analysis was done with SPSS. Sensitivity, specificity, positive and negative predictive values of TZI-as a method of assessing clinical BPH-were measured. Results There was a statistically significant difference in prostate volume, uroflowmetry patterns, prostate-specific antigen (PSA, International prostate symptom score (IPSS, TZV and TZI between the two groups. There was a correlation between TZV and the amount of resected tissue (r=0.97; p0.40 has a high level of sensitivity and specificity in the prediction of clinical BPH among patients who undergo TUR-P due to obstructive symptoms and reported as BPH. There is a strong correlation between the amount of resected tissue and TZV. TZI is a valuable tool in diagnosis, and TZV gives valuable information about the patient to the surgeon.

  9. The Prostate Health Index in predicting initial prostate biopsy outcomes in Asian men with prostate-specific antigen levels of 4-10 ng/mL.

    Science.gov (United States)

    Ng, C F; Chiu, Peter K F; Lam, N Y; Lam, H C; Lee, Kim W M; Hou, Simon S M

    2014-04-01

    To investigate the role of the Prostate Health Index (phi) in prostate cancer (PCa) detection in patients with a prostate-specific antigen (PSA) level of 4-10 ng/mL receiving their first prostatic biopsy in an Asian population. This was a retrospective study of archived serum samples from patients enlisted in our tissue bank. Patients over 50 years old, with PSA level of 4-10 ng/mL, a negative digital rectal examination, and received their first prostatic biopsy between April 2008 and April 2013, were recruited. The serum sample collected before biopsy was retrieved for the measurement of various PSA derivatives and the phi value was calculated for each patient. The performance of these parameters in predicting the prostatic biopsy results was assessed. Two hundred and thirty consecutive patients, with 21 (9.13 %) diagnosed with PCa, were recruited for this study. Statistically significant differences between PCa patients and non-PCa patients were found for total PSA, PSA density, [-2]proPSA (p2PSA), free-to-total PSA ratio (%fPSA), p2PSA-to-free PSA ratio (%p2PSA), and phi. The areas under the curve of the receiver operating characteristic curve for total PSA, PSA density, %fPSA, %p2PSA, and phi were 0.547, 0.634, 0.654, 0.768, and 0.781, respectively. The phi was the best predictor of the prostatic biopsies results. At a sensitivity of 90 %, the use of the phi could have avoided unnecessary biopsies in 104 (45.2 %) patients. Use of the phi could improve the accuracy of PCa detection in patients with an elevated PSA level and thus avoid unnecessary prostatic biopsies.

  10. Hydrodynamic cavitation kills prostate cells and ablates benign prostatic hyperplasia tissue.

    Science.gov (United States)

    Itah, Zeynep; Oral, Ozlem; Perk, Osman Yavuz; Sesen, Muhsincan; Demir, Ebru; Erbil, Secil; Dogan-Ekici, A Isin; Ekici, Sinan; Kosar, Ali; Gozuacik, Devrim

    2013-11-01

    Hydrodynamic cavitation is a physical phenomenon characterized by vaporization and bubble formation in liquids under low local pressures, and their implosion following their release to a higher pressure environment. Collapse of the bubbles releases high energy and may cause damage to exposed surfaces. We recently designed a set-up to exploit the destructive nature of hydrodynamic cavitation for biomedical purposes. We have previously shown that hydrodynamic cavitation could kill leukemia cells and erode kidney stones. In this study, we analyzed the effects of cavitation on prostate cells and benign prostatic hyperplasia (BPH) tissue. We showed that hydrodynamic cavitation could kill prostate cells in a pressure- and time-dependent manner. Cavitation did not lead to programmed cell death, i.e. classical apoptosis or autophagy activation. Following the application of cavitation, we observed no prominent DNA damage and cells did not arrest in the cell cycle. Hence, we concluded that cavitation forces directly damaged the cells, leading to their pulverization. Upon application to BPH tissues from patients, cavitation could lead to a significant level of tissue destruction. Therefore similar to ultrasonic cavitation, we propose that hydrodynamic cavitation has the potential to be exploited and developed as an approach for the ablation of aberrant pathological tissues, including BPH.

  11. Differentiation of prostate cancer from normal prostate tissue in an animal model: conventional MRI and dynamic contrast-enhanced MRI

    International Nuclear Information System (INIS)

    Gemeinhardt, O.; Prochnow, D.; Taupitz, M.; Hamm, B.; Beyersdorff, D.; Luedemann, L.; Abramjuk, C.

    2005-01-01

    Purpose: to differentiate orthotopically implanted prostate cancer from normal prostate tissue using magnetic resonance imaging (MRI) and Gd-DTPA-BMA-enhanced dynamic MRI in the rat model. Material and methods: tumors were induced in 15 rats by orthotopic implantation of G subline Dunning rat prostatic tumor cells. MRI was performed 56 to 60 days after tumor cell implantation using T1-weighted spin-echo, T2-weighted turbo SE sequences, and a 2D FLASH sequence for the contrast medium based dynamic study. The interstitial leakage volume, normalized permeability and the permeability surface area product of tumor and healthy prostate were determined quantitatively using a pharmacokinetic model. The results were confirmed by histologic examination. Results: axial T2-weighted TSE images depicted low-intensity areas suspicious for tumor in all 15 animals. The mean tumor volume was 46.5 mm3. In the dynamic study, the suspicious areas in all animals displayed faster and more pronounced signal enhancement than surrounding prostate tissue. The interstitial volume and the permeability surface area product of the tumors increased significantly by 420% (p<0.001) and 424% (p<0.001), respectively, compared to normal prostate tissue, while no significant difference was seen for normalized permeability alone. Conclusion: the results of the present study demonstrate that quantitative analysis of contrast-enhanced dynamic MRI data enables differentiation of small, slowly growing orthotopic prostate cancer from normal prostate tissue in the rat model. (orig.)

  12. Tissue polypeptide-specific antigen (TPS) determinations before and during intermittent maximal androgen blockade in patients with metastatic prostatic carcinoma

    NARCIS (Netherlands)

    Kil, P. J. M.; Goldschmidt, H. M. J.; Wieggers, B. J. A.; Kariakine, O. B.; Studer, U. E.; Whelan, P.; Hetherington, J.; de Reijke, Th M.; Hoekstra, J. W.; Collette, L.

    2003-01-01

    To evaluate the prognostic significance of serially measured tissue polypeptide-specific antigen (TPS) levels in patients with metastatic prostatic carcinoma treated with intermittent maximal androgen blockade (MAB). To determine its value with respect to predicting response to treatment and time to

  13. Prostate-specific antigen and long-term prediction of prostate cancer incidence and mortality in the general population

    DEFF Research Database (Denmark)

    Ørsted, David Dynnes; Nordestgaard, Børge G; Jensen, Gorm B

    2012-01-01

    It is largely unknown whether prostate-specific antigen (PSA) level at first date of testing predicts long-term risk of prostate cancer (PCa) incidence and mortality in the general population.......It is largely unknown whether prostate-specific antigen (PSA) level at first date of testing predicts long-term risk of prostate cancer (PCa) incidence and mortality in the general population....

  14. Convolutional neural networks for prostate cancer recurrence prediction

    Science.gov (United States)

    Kumar, Neeraj; Verma, Ruchika; Arora, Ashish; Kumar, Abhay; Gupta, Sanchit; Sethi, Amit; Gann, Peter H.

    2017-03-01

    Accurate prediction of the treatment outcome is important for cancer treatment planning. We present an approach to predict prostate cancer (PCa) recurrence after radical prostatectomy using tissue images. We used a cohort whose case vs. control (recurrent vs. non-recurrent) status had been determined using post-treatment follow up. Further, to aid the development of novel biomarkers of PCa recurrence, cases and controls were paired based on matching of other predictive clinical variables such as Gleason grade, stage, age, and race. For this cohort, tissue resection microarray with up to four cores per patient was available. The proposed approach is based on deep learning, and its novelty lies in the use of two separate convolutional neural networks (CNNs) - one to detect individual nuclei even in the crowded areas, and the other to classify them. To detect nuclear centers in an image, the first CNN predicts distance transform of the underlying (but unknown) multi-nuclear map from the input HE image. The second CNN classifies the patches centered at nuclear centers into those belonging to cases or controls. Voting across patches extracted from image(s) of a patient yields the probability of recurrence for the patient. The proposed approach gave 0.81 AUC for a sample of 30 recurrent cases and 30 non-recurrent controls, after being trained on an independent set of 80 case-controls pairs. If validated further, such an approach might help in choosing between a combination of treatment options such as active surveillance, radical prostatectomy, radiation, and hormone therapy. It can also generalize to the prediction of treatment outcomes in other cancers.

  15. Development of Interpretable Predictive Models for BPH and Prostate Cancer.

    Science.gov (United States)

    Bermejo, Pablo; Vivo, Alicia; Tárraga, Pedro J; Rodríguez-Montes, J A

    2015-01-01

    Traditional methods for deciding whether to recommend a patient for a prostate biopsy are based on cut-off levels of stand-alone markers such as prostate-specific antigen (PSA) or any of its derivatives. However, in the last decade we have seen the increasing use of predictive models that combine, in a non-linear manner, several predictives that are better able to predict prostate cancer (PC), but these fail to help the clinician to distinguish between PC and benign prostate hyperplasia (BPH) patients. We construct two new models that are capable of predicting both PC and BPH. An observational study was performed on 150 patients with PSA ≥3 ng/mL and age >50 years. We built a decision tree and a logistic regression model, validated with the leave-one-out methodology, in order to predict PC or BPH, or reject both. Statistical dependence with PC and BPH was found for prostate volume (P-value BPH prediction. PSA and volume together help to build predictive models that accurately distinguish among PC, BPH, and patients without any of these pathologies. Our decision tree and logistic regression models outperform the AUC obtained in the compared studies. Using these models as decision support, the number of unnecessary biopsies might be significantly reduced.

  16. Ectopic prostatic tissue in the rectum: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Seol, Myung Jin; Noh, Kyung Hee; Jeon, Doo Sung; Lee, Kwang Min [Presbyterian Medical Center, Jeonju (Korea, Republic of)

    2017-02-15

    Ectopic prostatic tissue (EPT) outside the male genitourinary tract is an unusual finding, and it is very rarely found in the rectum or around the peri-rectal region. In addition, the radiologic features of EPT are seldom reported. Also, it is difficult to differentiate EPT found in the rectal subepithelium from the other types of subepithelial tumors. We present here a unique case of EPT found in the retrorectal region, along with the radiologic findings of transrectal ultrasonography, computed tomography, and magnetic resonance imaging with their pathologic correlations.

  17. X-ray fluorescence microtomography analyzing prostate tissues

    International Nuclear Information System (INIS)

    Pereira, Gabriela R.; Rocha, Henrique S.; Calza, Cristiane; Lopes, Ricardo T.

    2009-01-01

    The objective of this work is to determine the elemental distribution map in reference samples and prostate tissue samples using X-Ray Fluorescence Microtomography (XRFCT) in order to verify concentrations of certain elements correlated with characteristics observed by the transmission microtomography. The experiments were performed at the X-Ray Fluorescence Facility of the Brazilian Synchrotron Light Laboratory. A quasi-monochromatic beam produced by a multilayer monochromator was used as an incident beam. The transmission CT images were reconstructed using filtered-back-projection algorithm, and the XRFCT images were reconstructed using filtered-back-projection algorithm with absorption corrections. (author)

  18. Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error.

    Science.gov (United States)

    Shipitsin, M; Small, C; Choudhury, S; Giladi, E; Friedlander, S; Nardone, J; Hussain, S; Hurley, A D; Ernst, C; Huang, Y E; Chang, H; Nifong, T P; Rimm, D L; Dunyak, J; Loda, M; Berman, D M; Blume-Jensen, P

    2014-09-09

    Key challenges of biopsy-based determination of prostate cancer aggressiveness include tumour heterogeneity, biopsy-sampling error, and variations in biopsy interpretation. The resulting uncertainty in risk assessment leads to significant overtreatment, with associated costs and morbidity. We developed a performance-based strategy to identify protein biomarkers predictive of prostate cancer aggressiveness and lethality regardless of biopsy-sampling variation. Prostatectomy samples from a large patient cohort with long follow-up were blindly assessed by expert pathologists who identified the tissue regions with the highest and lowest Gleason grade from each patient. To simulate biopsy-sampling error, a core from a high- and a low-Gleason area from each patient sample was used to generate a 'high' and a 'low' tumour microarray, respectively. Using a quantitative proteomics approach, we identified from 160 candidates 12 biomarkers that predicted prostate cancer aggressiveness (surgical Gleason and TNM stage) and lethal outcome robustly in both high- and low-Gleason areas. Conversely, a previously reported lethal outcome-predictive marker signature for prostatectomy tissue was unable to perform under circumstances of maximal sampling error. Our results have important implications for cancer biomarker discovery in general and development of a sampling error-resistant clinical biopsy test for prediction of prostate cancer aggressiveness.

  19. Experimental study of apoptosis in the prostate tissue following castration

    Directory of Open Access Journals (Sweden)

    Y Doustar

    2008-02-01

    Full Text Available The Prostate gland is one of the accessory reproductive glands with important physiological functions necessary for successful reproduction. This gland depends on the presence of sex hormones including androgens for its natural function and normal growth and development. So in the case of hyperplasia, hypertrophy or other prostatic disease the most successful and efficient method of treatment is androgenic control that in some cases is unavoidable. The purpose of this study was to investigate the effects of androgenic depletion states by means of castration on the induction of apoptosis in the epithelial glandular cells of the prostate tissue. Two groups of male dogs each containing 5 animals per group were used in this study. The dogs were under observation for 1 month to detect any possible diseases or disorders. After this period the dogs in the treatment group underwent open castration to decrease the levels of the androgenic hormones in the blood while the dogs in the control group were left intact. One week after surgery, the prostate glands of control and treatment animals were collected and used to prepare microscopic sections. The sections were evaluated following staining with TUNEL (TerminaldeoxyNucleotidyl (dUTP transferase-mediated End Labeling and H&E methods. The Mann – Whitney U test was used for statistical analysis. Histopathological studies in the treatment group revealed the presence of various forms of apoptotic cells in the glandular epithelium. Average number of apoptotic cells in ten microscopic fields were significantly higher in the treatment group compared with the control group (p

  20. Endoscopic assessment and prediction of prostate urethral disintegration after histotripsy treatment in a canine model.

    Science.gov (United States)

    Schade, George R; Styn, Nicholas R; Hall, Timothy L; Roberts, William W

    2012-02-01

    Histotripsy is a nonthermal focused ultrasound technology that uses acoustic cavitation to homogenize tissue. Previous research has demonstrated that the prostatic urethra is more resistant to histotripsy effects than prostate parenchyma, a finding that may complicate the creation of transurethral resection of the prostate-like treatment cavities. The purpose of this study was to characterize the endoscopic appearance of the prostatic urethra during and after histotripsy treatment and to identify features that are predictive of urethral disintegration. Thirty-five histotripsy treatments were delivered in a transverse plane traversing the prostatic urethra in 17 canine subjects (1-3/prostate ≥1 cm apart). Real-time endoscopy was performed in the first four subjects to characterize development of acute urethral treatment effect (UTE). Serial postprocedure endoscopy was performed in all subjects to assess subsequent evolution of UTE. Endoscopy during histotripsy was feasible with observation of intraurethral cavitation, allowing characterization of the real-time progression of UTE from normal to frank urethral disintegration. While acute urethral fragmentation occurred in 3/35 (8.6%) treatments, frank urethral disintegration developed in 24/35 (68.5%) within 14 days of treatment. Treating until the appearance of hemostatic pale gray shaggy urothelium was the best predictor of achieving urethral fragmentation within 14 days of treatment with positive and negative predictive values of 0.91 and 0.89, respectively. Endoscopic assessment of the urethra may be a useful adjunct to prostatic histotripsy to help guide therapy to ensure urethral disintegration, allowing drainage of the homogenized adenoma and effective tissue debulking.

  1. Predicting prostate biopsy outcome: prostate health index (phi) and prostate cancer antigen 3 (PCA3) are useful biomarkers.

    Science.gov (United States)

    Ferro, Matteo; Bruzzese, Dario; Perdonà, Sisto; Mazzarella, Claudia; Marino, Ada; Sorrentino, Alessandra; Di Carlo, Angelina; Autorino, Riccardo; Di Lorenzo, Giuseppe; Buonerba, Carlo; Altieri, Vincenzo; Mariano, Angela; Macchia, Vincenzo; Terracciano, Daniela

    2012-08-16

    Indication for prostate biopsy is presently mainly based on prostate-specific antigen (PSA) serum levels and digital-rectal examination (DRE). In view of the unsatisfactory accuracy of these two diagnostic exams, research has focused on novel markers to improve pre-biopsy prostate cancer detection, such as phi and PCA3. The purpose of this prospective study was to assess the diagnostic accuracy of phi and PCA3 for prostate cancer using biopsy as gold standard. Phi index (Beckman coulter immunoassay), PCA3 score (Progensa PCA3 assay) and other established biomarkers (tPSA, fPSA and %fPSA) were assessed before a 18-core prostate biopsy in a group of 251 subjects at their first biopsy. Values of %p2PSA and phi were significantly higher in patients with PCa compared with PCa-negative group (pphi and PCA3 are predictive of malignancy. In conclusion, %p2PSA, phi and PCA3 may predict a diagnosis of PCa in men undergoing their first prostate biopsy. PCA3 score is more useful in discriminating between HGPIN and non-cancer. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Combined spectroscopic imaging and chemometric approach for automatically partitioning tissue types in human prostate tissue biopsies

    Science.gov (United States)

    Haka, Abigail S.; Kidder, Linda H.; Lewis, E. Neil

    2001-07-01

    We have applied Fourier transform infrared (FTIR) spectroscopic imaging, coupling a mercury cadmium telluride (MCT) focal plane array detector (FPA) and a Michelson step scan interferometer, to the investigation of various states of malignant human prostate tissue. The MCT FPA used consists of 64x64 pixels, each 61 micrometers 2, and has a spectral range of 2-10.5 microns. Each imaging data set was collected at 16-1 resolution, resulting in 512 image planes and a total of 4096 interferograms. In this article we describe a method for separating different tissue types contained within FTIR spectroscopic imaging data sets of human prostate tissue biopsies. We present images, generated by the Fuzzy C-Means clustering algorithm, which demonstrate the successful partitioning of distinct tissue type domains. Additionally, analysis of differences in the centroid spectra corresponding to different tissue types provides an insight into their biochemical composition. Lastly, we demonstrate the ability to partition tissue type regions in a different data set using centroid spectra calculated from the original data set. This has implications for the use of the Fuzzy C-Means algorithm as an automated technique for the separation and examination of tissue domains in biopsy samples.

  3. Two cases of benign polyps of the posterior urethra (ectopic prostatic tissue)

    OpenAIRE

    多田, 晃司; 山羽, 正義; 田村, 公一; 藤広, 茂; 河田, 幸道

    1990-01-01

    We report two cases of benign polyps of the posterior urethra. Their first symptoms were gross hematuria and urinary frequency. Both specimens obtained by transurethral resection were histologically identified as prostatic tissue. Discussion on benign polyps of the posterior urethra as ectopic prostatic tissue was done with review of literature.

  4. Prediction of PSA bounce after permanent prostate brachytherapy for localized prostate cancer

    International Nuclear Information System (INIS)

    Kanai, Kunimitsu; Nakashima, Jun; Sugawara, Akitomo

    2009-01-01

    We aimed to calculate the frequency and features of the development of a prostate-specific antigen (PSA) bounce after prostate brachytherapy alone, to correlate the bounce with clinical and dosimetric factors and to identify factors that predict PSA bounce. PSA bounce was evaluated in 86 patients with T1-T2 prostate cancer who underwent radioactive seed implantation using iodine-125 (I-125) without hormonal therapy or external-beam radiation therapy (EBRT) from September 2004 to December 2007. A PSA bounce was defined as a rise of at least 0.4 ng/ml greater than a previous PSA level with a subsequent decline equal to, or less than, the initial nadir. Calculated by the Kaplan-Meier method, the incidence of PSA bounce at a 2-year follow-up was 26%. Median time to the PSA bounce was 15 months. Univariate analysis demonstrated that age, dose received by 90% of the prostate gland (D90), volume of gland receiving 100% of the prescribed dose (V100), and V150 were significantly associated with the PSA bounce, while pretreatment PSA level, Gleason score, pretreatment prostate volume, clinical T stage, and V200 were not. In multivariate analysis, age 67 years or less and D90 more than 180 Gy were identified as independent factors for predicting the PSA bounce (P<0.05). PSA bounce is not a rare phenomenon after prostate brachytherapy. It is more common in younger patients and patients receiving higher doses of radiation. (author)

  5. Assessment of cone beam CT registration for prostate radiation therapy: fiducial marker and soft tissue methods.

    Science.gov (United States)

    Deegan, Timothy; Owen, Rebecca; Holt, Tanya; Fielding, Andrew; Biggs, Jennifer; Parfitt, Matthew; Coates, Alicia; Roberts, Lisa

    2015-02-01

    This investigation aimed to assess the consistency and accuracy of radiation therapists (RTs) performing cone beam computed tomography (CBCT) alignment to fiducial markers (FMs) (CBCTFM ) and the soft tissue prostate (CBCTST ). Six patients receiving prostate radiation therapy underwent daily CBCTs. Manual alignment of CBCTFM and CBCTST was performed by three RTs. Inter-observer agreement was assessed using a modified Bland-Altman analysis for each alignment method. Clinically acceptable 95% limits of agreement with the mean (LoAmean ) were defined as ±2.0 mm for CBCTFM and ±3.0 mm for CBCTST . Differences between CBCTST alignment and the observer-averaged CBCTFM (AvCBCTFM ) alignment were analysed. Clinically acceptable 95% LoA were defined as ±3.0 mm for the comparison of CBCTST and AvCBCTFM . CBCTFM and CBCTST alignments were performed for 185 images. The CBCTFM 95% LoAmean were within ±2.0 mm in all planes. CBCTST 95% LoAmean were within ±3.0 mm in all planes. Comparison of CBCTST with AvCBCTFM resulted in 95% LoA of -4.9 to 2.6, -1.6 to 2.5 and -4.7 to 1.9 mm in the superior-inferior, left-right and anterior-posterior planes, respectively. Significant differences were found between soft tissue alignment and the predicted FM position. FMs are useful in reducing inter-observer variability compared with soft tissue alignment. Consideration needs to be given to margin design when using soft tissue matching due to increased inter-observer variability. This study highlights some of the complexities of soft tissue guidance for prostate radiation therapy. © 2014 The Royal Australian and New Zealand College of Radiologists.

  6. Assessment of cone beam CT registration for prostate radiation therapy: fiducial marker and soft tissue methods

    International Nuclear Information System (INIS)

    Deegan, Timothy; Owen, Rebecca; Holt, Tanya; Fielding, Andrew; Biggs, Jennifer; Parfitt, Matthew; Coates, Alicia; Roberts, Lisa

    2015-01-01

    This investigation aimed to assess the consistency and accuracy of radiation therapists (RTs) performing cone beam computed tomography (CBCT) alignment to fiducial markers (FMs) (CBCT FM ) and the soft tissue prostate (CBCT ST ). Six patients receiving prostate radiation therapy underwent daily CBCTs. Manual alignment of CBCT FM and CBCT ST was performed by three RTs. Inter-observer agreement was assessed using a modified Bland–Altman analysis for each alignment method. Clinically acceptable 95% limits of agreement with the mean (LoA mean ) were defined as ±2.0 mm for CBCT FM and ±3.0 mm for CBCT ST . Differences between CBCT ST alignment and the observer-averaged CBCT FM (AvCBCT FM ) alignment were analysed. Clinically acceptable 95% LoA were defined as ±3.0 mm for the comparison of CBCT ST and AvCBCT FM . CBCT FM and CBCT ST alignments were performed for 185 images. The CBCT FM 95% LoA mean were within ±2.0 mm in all planes. CBCT ST 95% LoA mean were within ±3.0 mm in all planes. Comparison of CBCT ST with AvCBCT FM resulted in 95% LoA of −4.9 to 2.6, −1.6 to 2.5 and −4.7 to 1.9 mm in the superior–inferior, left–right and anterior–posterior planes, respectively. Significant differences were found between soft tissue alignment and the predicted FM position. FMs are useful in reducing inter-observer variability compared with soft tissue alignment. Consideration needs to be given to margin design when using soft tissue matching due to increased inter-observer variability. This study highlights some of the complexities of soft tissue guidance for prostate radiation therapy.

  7. Gene expression profiling of prostate tissue identifies chromatin regulation as a potential link between obesity and lethal prostate cancer.

    Science.gov (United States)

    Ebot, Ericka M; Gerke, Travis; Labbé, David P; Sinnott, Jennifer A; Zadra, Giorgia; Rider, Jennifer R; Tyekucheva, Svitlana; Wilson, Kathryn M; Kelly, Rachel S; Shui, Irene M; Loda, Massimo; Kantoff, Philip W; Finn, Stephen; Vander Heiden, Matthew G; Brown, Myles; Giovannucci, Edward L; Mucci, Lorelei A

    2017-11-01

    Obese men are at higher risk of advanced prostate cancer and cancer-specific mortality; however, the biology underlying this association remains unclear. This study examined gene expression profiles of prostate tissue to identify biological processes differentially expressed by obesity status and lethal prostate cancer. Gene expression profiling was performed on tumor (n = 402) and adjacent normal (n = 200) prostate tissue from participants in 2 prospective cohorts who had been diagnosed with prostate cancer from 1982 to 2005. Body mass index (BMI) was calculated from the questionnaire immediately preceding cancer diagnosis. Men were followed for metastases or prostate cancer-specific death (lethal disease) through 2011. Gene Ontology biological processes differentially expressed by BMI were identified using gene set enrichment analysis. Pathway scores were computed by averaging the signal intensities of member genes. Odds ratios (ORs) for lethal prostate cancer were estimated with logistic regression. Among 402 men, 48% were healthy weight, 31% were overweight, and 21% were very overweight/obese. Fifteen gene sets were enriched in tumor tissue, but not normal tissue, of very overweight/obese men versus healthy-weight men; 5 of these were related to chromatin modification and remodeling (false-discovery rate 7, 41% vs 17%; P = 2 × 10 -4 ) and an increased risk of lethal disease that was independent of grade and stage (OR, 5.26; 95% confidence interval, 2.37-12.25). This study improves our understanding of the biology of aggressive prostate cancer and identifies a potential mechanistic link between obesity and prostate cancer death that warrants further study. Cancer 2017;123:4130-4138. © 2017 American Cancer Society. © 2017 American Cancer Society.

  8. A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

    Directory of Open Access Journals (Sweden)

    Thorsten Schlomm

    2013-03-01

    Full Text Available We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA levels (14 and 17 individuals, respectively were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs. Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b, which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ.

  9. Prostate cancer volume adds significantly to prostate-specific antigen in the prediction of early biochemical failure after external beam radiation therapy

    International Nuclear Information System (INIS)

    D'Amico, Anthony V.; Propert, Kathleen J.

    1996-01-01

    Purpose: A new clinical pretreatment quantity that closely approximates the true prostate cancer volume is defined. Methods and Materials: The cancer-specific prostate-specific antigen (PSA), PSA density, prostate cancer volume (V Ca ), and the volume fraction of the gland involved with carcinoma (V Ca fx) were calculated for 227 prostate cancer patients managed definitively with external beam radiation therapy. 1. PSA density PSA/ultrasound prostate gland volume 2. Cancer-specific PSA = PSA - [PSA from benign epithelial tissue] 3. V Ca = Cancer-specific PSA/[PSA in serum per cm 3 of cancer] 4. V Ca fx = V Ca /ultrasound prostate gland volume A Cox multiple regression analysis was used to test whether any of these-clinical pretreatment parameters added significantly to PSA in predicting early postradiation PSA failure. Results: The prostate cancer volume (p = 0.039) and the volume fraction of the gland involved by carcinoma (p = 0.035) significantly added to the PSA in predicting postradiation PSA failure. Conversely, the PSA density and the cancer-specific PSA did not add significantly (p > 0.05) to PSA in predicting postradiation PSA failure. The 20-month actuarial PSA failure-free rates for patients with calculated tumor volumes of ≤0.5 cm 3 , 0.5-4.0 cm 3 , and >4.0 cm 3 were 92, 80, and 47%, respectively (p = 0.00004). Conclusion: The volume of prostate cancer (V Ca ) and the resulting volume fraction of cancer both added significantly to PSA in their ability to predict for early postradiation PSA failure. These new parameters may be used to select patients in prospective randomized trials that examine the efficacy of combining radiation and androgen ablative therapy in patients with clinically localized disease, who are at high risk for early postradiation PSA failure

  10. The Addition of Manganese Porphyrins during Radiation Inhibits Prostate Cancer Growth and Simultaneously Protects Normal Prostate Tissue from Radiation Damage

    Directory of Open Access Journals (Sweden)

    Arpita Chatterjee

    2018-01-01

    Full Text Available Radiation therapy is commonly used for prostate cancer treatment; however, normal tissues can be damaged from the reactive oxygen species (ROS produced by radiation. In separate reports, we and others have shown that manganese porphyrins (MnPs, ROS scavengers, protect normal cells from radiation-induced damage but inhibit prostate cancer cell growth. However, there have been no studies demonstrating that MnPs protect normal tissues, while inhibiting tumor growth in the same model. LNCaP or PC3 cells were orthotopically implanted into athymic mice and treated with radiation (2 Gy, for 5 consecutive days in the presence or absence of MnPs. With radiation, MnPs enhanced overall life expectancy and significantly decreased the average tumor volume, as compared to the radiated alone group. MnPs enhanced lipid oxidation in tumor cells but reduced oxidative damage to normal prostate tissue adjacent to the prostate tumor in combination with radiation. Mechanistically, MnPs behave as pro-oxidants or antioxidants depending on the level of oxidative stress inside the treated cell. We found that MnPs act as pro-oxidants in prostate cancer cells, while in normal cells and tissues the MnPs act as antioxidants. For the first time, in the same in vivo model, this study reveals that MnPs enhance the tumoricidal effect of radiation and reduce oxidative damage to normal prostate tissue adjacent to the prostate tumor in the presence of radiation. This study suggests that MnPs are effective radio-protectors for radiation-mediated prostate cancer treatment.

  11. FOXP3+ regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer.

    Science.gov (United States)

    Davidsson, Sabina; Andren, Ove; Ohlson, Anna-Lena; Carlsson, Jessica; Andersson, Swen-Olof; Giunchi, Francesca; Rider, Jennifer R; Fiorentino, Michelangelo

    2018-01-01

    The tumor promoting or counteracting effects of the immune response to cancer development are thought to be mediated to some extent by the infiltration of regulatory T cells (T regs ). In the present study we evaluated the prevalence of T reg populations in stromal and epithelial compartments of normal, post atrophic hyperplasia (PAH), prostatic intraepithelial neoplasia (PIN), and tumor lesions in men with and without prostate cancer. Study subjects were 102 men consecutively diagnosed with localized prostate cancer undergoing radical prostatectomy and 38 men diagnosed with bladder cancer undergoing cystoprostatectomy without prostate cancer at the pathological examination. Whole mount sections from all patients were evaluated for the epithelial and stromal expression of CD4 + T regs and CD8 + T regs in normal, PAH, PIN, and tumor lesions. A Friedmańs test was used to investigate differences in the mean number of T regs across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area. In men with prostate cancer, similarly high numbers of stromal CD4 + T regs were identified in PAH and tumor, but CD4 + T regs were less common in PIN. Greater numbers of epithelial CD4+ T regs in normal prostatic tissue were positively associated with both Gleason score and pT-stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4 + T regs in the normal prostatic tissue counterpart. Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4 + T regs and indicate that transformation of the anti-tumor immune response may be initiated even before the primary tumor is established. © 2017 The Authors. The Prostate Published by Wiley Periodicals Inc.

  12. Penetration and pharmacokinetics of non-steroidal anti-inflammatory drugs in rat prostate tissue.

    Science.gov (United States)

    Yellepeddi, Venkata K; Radhakrishnan, Jayashree; Radhakrishnan, Rajan

    2018-02-01

    Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) involves inflammation of the prostate and affects the quality of life of men of all ages. It is well reported in clinical studies that the treatment for CP/CPPS using nonsteroidal anti-inflammatory drugs (NSAIDs) produced favorable outcomes. However, currently, there are no guidelines on choice of the NSAIDs for the treatment of CP/CPPS. Therefore, in the current research study, we evaluated the prostate tissue penetration of four NSAIDs in rats to provide guidance on choice of NSAIDs for the treatment of CP/CPPS. Male Sprague-Dawley rats were administered orally with four NSAIDs viz. celecoxib, diclofenac, ibuprofen, and naproxen at 500 mg/kg dose. The animals were then sacrificed at various time points, and their prostate tissues were harvested. The NSAIDs were then extracted from the prostate tissues using liquid extraction technique, and their concentration in prostate tissue was quantified using high-performance liquid chromatography (HPLC). The prostate tissue penetration and related pharmacokinetic parameters were evaluated by non-compartmental analysis. The HPLC method for quantifying NSAIDs in prostate tissue resulted in single, sharp peaks without any interference and all validation parameters were within limits. Celecoxib showed the highest area under the curve (AUC) [146.50 ± 2.75 μg/mL*h] of all NSAID's. A two-factor analysis of variance (ANOVA) with replication indicated an overall statistically significant difference in the pharmacokinetic parameters for celecoxib, diclofenac, ibuprofen, and naproxen. This study for the first time reported the relative prostate tissue penetration of four NSAIDs. The pharmacokinetic data indicated that celecoxib has the highest penetration and retention in rat prostate tissues. Therefore, celecoxib may be considered as a better choice for the treatment CP/CPPS involving NSAIDs. © 2017 Wiley Periodicals, Inc.

  13. Factors predicting for postimplantation urinary retention after permanent prostate brachytherapy

    International Nuclear Information System (INIS)

    Lee, Nancy; Wuu, C.-S.; Brody, Rachel; Laguna, Joe L.; Katz, Aaron E.; Bagiella, Emilia; Ennis, Ronald D.

    2000-01-01

    Purpose: Urinary retention requiring catheterization is a known complication among prostate cancer patients treated with permanent interstitial radioactive seed implantation. However, the factors associated with this complication are not well known. This study was conducted to determine these factors. Methods and Materials: Ninety-one consecutive prostate cancer patients treated with permanent interstitial implantation at our institution from 1996 to 1999 were evaluated. All patients underwent pre-implant ultrasound and postimplant CT volume studies. Isotopes used were 125 I (54 patients) or 103 Pd (37 patients). Twenty-three patients were treated with a combination of 45 Gy of external beam radiation therapy as well as seed implantation, of which only 3 patients were treated with 125 I. Mean pretreatment prostate ultrasound volume was 35.4 cc (range, 10.0-70.2 cc). The mean planning ultrasound target volume (PUTV) was 39.6 cc (range, 16.1-74.5 cc), whereas the mean posttreatment CT target volume was 55.0 cc (range, 20.2-116 cc). Patient records were reviewed to determine which patients required urinary catheterization for relief of urinary obstruction. The following factors were analyzed as predictors for urinary retention: clinical stage; Gleason score; prostate-specific antigen; external beam radiation therapy; hormone therapy; pre-implant urinary symptoms (asymptomatic/nocturia x 1 vs. more significant urinary symptoms); pretreatment ultrasound prostate volume; PUTV; PUTV within the 125%, 150%, 200%, 250%, 300% isodose lines; postimplant CT volume within the 125%, 150%, 200%, 250%, 300% isodose lines; D90; D80; D50; ratio of post-CT volume to the PUTV; the absolute change in volume between the CT volume and PUTV; number of needles used; activity per seed; and the total activity of the implant. Statistical analyses using logistic regression and χ2 were performed. Results: Eleven of 91 (12%) became obstructed. Significant factors predicting for urinary retention

  14. Fluorescence spectra of benign and malignant prostate tissues

    International Nuclear Information System (INIS)

    AlSalhi, M S; Masilamani, V; Atif, M; Farhat, K; Rabah, D; Al Turki, M R

    2012-01-01

    In this study, fluorescence emission spectrum (FES), Stokes' shift spectrum (SSS), and reflectance spectrum (RS) of benign (N = 12) and malignant prostate tissues (N = 8) were investigated to discriminate the two types of tissues. The FES was done with the excitation at 325 nm only; SSS with Δλ = 70 and Δλ = 0, the latter being equivalent to reflectance spectra. Of the three modes of spectra, SSS with Δλ = 70 nm showed the best discrimination. There were four important bands, one at 280 nm (due to tryptophan); 320 nm (due to elastin and tryptophan); 355 and 385 (due to NADH) and 440 nm (due to flavin). From the relative intensities of these bands, three ratios were evaluated. Similarly another two ratios were obtained from reflectance spectra and one more from FES. Thus, there are 6 ratio parameters which represent the relative concentration of tryptophan, elastin, nicotinamide adenine dinucleotide (NADH), and flavin. A statistical analysis showed that benign and malignant tissues could be classified with accuracy greater than 90%. This report is only for in vitro analysis; but employing optical fiber, this can be extended to in vivo analysis too, so that benign tumor could be distinguished without surgery

  15. Voxel-wise prostate cell density prediction using multiparametric magnetic resonance imaging and machine learning.

    Science.gov (United States)

    Sun, Yu; Reynolds, Hayley M; Wraith, Darren; Williams, Scott; Finnegan, Mary E; Mitchell, Catherine; Murphy, Declan; Haworth, Annette

    2018-04-26

    There are currently no methods to estimate cell density in the prostate. This study aimed to develop predictive models to estimate prostate cell density from multiparametric magnetic resonance imaging (mpMRI) data at a voxel level using machine learning techniques. In vivo mpMRI data were collected from 30 patients before radical prostatectomy. Sequences included T2-weighted imaging, diffusion-weighted imaging and dynamic contrast-enhanced imaging. Ground truth cell density maps were computed from histology and co-registered with mpMRI. Feature extraction and selection were performed on mpMRI data. Final models were fitted using three regression algorithms including multivariate adaptive regression spline (MARS), polynomial regression (PR) and generalised additive model (GAM). Model parameters were optimised using leave-one-out cross-validation on the training data and model performance was evaluated on test data using root mean square error (RMSE) measurements. Predictive models to estimate voxel-wise prostate cell density were successfully trained and tested using the three algorithms. The best model (GAM) achieved a RMSE of 1.06 (± 0.06) × 10 3 cells/mm 2 and a relative deviation of 13.3 ± 0.8%. Prostate cell density can be quantitatively estimated non-invasively from mpMRI data using high-quality co-registered data at a voxel level. These cell density predictions could be used for tissue classification, treatment response evaluation and personalised radiotherapy.

  16. Potential predictive factors of positive prostate biopsy in the Chinese ...

    African Journals Online (AJOL)

    Yomi

    2012-01-16

    Jan 16, 2012 ... Therefore, it might be inappropriate that we apply these western models to the. Chinese population that has a lower incidence of PCa. Therefore, this retrospective study aimed to determine predictive factors for a positive prostate biopsy in Chinese men. Our ultimate goal is to develop a simple model for ...

  17. Organoid culture systems for prostate epithelial and cancer tissue

    NARCIS (Netherlands)

    Drost, Jarno; Karthaus, Wouter R; Gao, Dong; Driehuis, Else; Sawyers, Charles L; Chen, Yu; Clevers, Hans

    This protocol describes a strategy for the generation of 3D prostate organoid cultures from healthy mouse and human prostate cells (either bulk or FACS-sorted single luminal and basal cells), metastatic prostate cancer lesions and circulating tumor cells. Organoids derived from healthy material

  18. Conversion of 3H-testosterone to dihydrotestosterone in human hypertrophic prostatic tissue

    International Nuclear Information System (INIS)

    Baranowska, B.; Zgliczynski

    1979-01-01

    The aim of the study was to develop a simple method for the determination of the conversion of testosterone to 5α-dihydrotestosterone (5α-DHT) after incubation of human hypertrophic prostatic tissue with 3 H-testosterone. The mean conversion rate of 3 H-testosterone to 5α-DHT in hypertrophic prostatic tissue was found to be higher than in normal and carcinomatous tissue. The results indicate that androgen metabolism in the hypertrophic prostatic gland is enhanced. (orig.) [de

  19. Conversion of /sup 3/H-testosterone to dihydrotestosterone in human hypertrophic prostatic tissue

    Energy Technology Data Exchange (ETDEWEB)

    Baranowska, B; Zgliczynski, [Centre of Postgraduate Medical Education, Warsaw (Poland). Clinic of Endocrinology

    1979-12-01

    The aim of the study was to develop a simple method for the determination of the conversion of testosterone to 5..cap alpha..-dihydrotestosterone (5..cap alpha..-DHT) after incubation of human hypertrophic prostatic tissue with /sup 3/H-testosterone. The mean conversion rate of /sup 3/H-testosterone to 5..cap alpha..-DHT in hypertrophic prostatic tissue was found to be higher than in normal and carcinomatous tissue. The results indicate that androgen metabolism in the hypertrophic prostatic gland is enhanced.

  20. Tissue specific and androgen-regulated expression of human prostate-specific transglutaminase

    NARCIS (Netherlands)

    H.J. Dubbink (Erik Jan); N.S. Verkaik (Nicole); P.W. Faber; J. Trapman (Jan); F.H. Schröder (Fritz); J.C. Romijn (Johannes)

    1996-01-01

    textabstractTransglutaminases (TGases) are calcium-dependent enzymes catalysing the post-translational cross-linking of proteins. In the prostate at least two TGases are present, the ubiquitously expressed tissue-type TGase (TGC), and a prostate-restricted TGase (TGP).

  1. Pilot Comparison of Stromal Gene Expression among Normal Prostate Tissues and Primary Prostate Cancer Tissues in White and Black Men

    National Research Council Canada - National Science Library

    Bova, G. S

    2006-01-01

    ..., and expression analysis of prostate-stroma specific cells in normal and cancerous prostates, and aims to develop preliminary data sufficient to identify potential differences in stromal RNA expression in normal and cancerous...

  2. Pilot Comparison of Stromal Gene Expression among Normal Prostate Tissues and Primary Prostate Cancer Tissues in White and Black Men

    National Research Council Canada - National Science Library

    Bova, G. S

    2006-01-01

    Recent advances in prostate biology suggest that stromal cells surrounding prostate epithelia may play a key role in permitting or stimulating epithelial cells to lose control and form precancerous and cancerous lesions...

  3. Perineural invasion on prostate needle biopsy does not predict biochemical failure following brachytherapy for prostate cancer

    International Nuclear Information System (INIS)

    Weight, Christopher J.; Ciezki, Jay P.; Reddy, Chandana A.; Zhou Ming; Klein, Eric A.

    2006-01-01

    Purpose: To determine if the presence of perineural invasion (PNI) predicts biochemical recurrence in patients who underwent low-dose-rate brachytherapy for the treatment of localized prostate cancer. Methods and Materials: A retrospective case control matching study was performed. The records of 651 patients treated with brachytherapy between 1996 and 2003 were reviewed. Sixty-three of these patients developed biochemical failure. These sixty-three patients were then matched in a one-to-one ratio to patients without biochemical failure, controlling for biopsy Gleason score, clinical stage, initial prostate-specific antigen, age, and the use of androgen deprivation. The pathology of the entire cohort was then reviewed for evidence of perineural invasion on initial prostate biopsy specimens. The biochemical relapse free survival rates for these two groups were compared. Results: Cases and controls were well matched, and there were no significant differences between the two groups in age, Gleason grade, clinical stage, initial prostate-specific antigen, and the use of androgen deprivation. PNI was found in 19 (17%) patients. There was no significant difference in the rates of PNI between cases and controls, 19.6% and 14.3% respectively (p 0.45). PNI did not correlate with biochemical relapse free survival (p 0.40). Conclusion: Perineural invasion is not a significant predictor of biochemical recurrence in patients undergoing brachytherapy for prostate cancer

  4. Estradiol suppresses tissue androgens and prostate cancer growth in castration resistant prostate cancer

    International Nuclear Information System (INIS)

    Montgomery, Bruce; Nelson, Peter S; Vessella, Robert; Kalhorn, Tom; Hess, David; Corey, Eva

    2010-01-01

    Estrogens suppress tumor growth in prostate cancer which progresses despite anorchid serum androgen levels, termed castration resistant prostate cancers (CRPC), although the mechanisms are unclear. We hypothesize that estrogen inhibits CRPC in anorchid animals by suppressing tumoral androgens, an effect independent of the estrogen receptor. The human CRPC xenograft LuCaP 35V was implanted into orchiectomized male SCID mice and established tumors were treated with placebo, 17β-estradiol or 17β-estradiol and estrogen receptor antagonist ICI 182,780. Effects of 17β-estradiol on tumor growth were evaluated and tissue testosterone (T) and dihydrotestosterone (DHT) evaluated by mass spectrometry. Treatment of LuCaP 35V with 17β-estradiol slowed tumor growth compared to controls (tumor volume at day 21: 785 ± 81 mm 3 vs. 1195 ± 84 mm 3 , p = 0.002). Survival was also significantly improved in animals treated with 17β-estradiol (p = 0.03). The addition of the estrogen receptor antagonist ICI 182,780 did not significantly change survival or growth. 17β-estradiol in the presence and absence of ICI 182,780 suppressed tumor testosterone (T) and dihydrotestosterone (DHT) as assayed by mass spectrometry. Tissue androgens in placebo treated LuCaP 35V xenografts were; T = 0.71 ± 0.28 pg/mg and DHT = 1.73 ± 0.36 pg/mg. In 17β-estradiol treated LuCaP35V xenografts the tissue androgens were, T = 0.20 ± 0.10 pg/mg and DHT = 0.15 ± 0.15 pg/mg, (p < 0.001 vs. controls). Levels of T and DHT in control liver tissue were < 0.2 pg/mg. CRPC in anorchid animals maintains tumoral androgen levels despite castration. 17β-estradiol significantly suppressed tumor T and DHT and inhibits growth of CRPC in an estrogen receptor independent manner. The ability to manipulate tumoral androgens will be critical in the development and testing of agents targeting CRPC through tissue steroidogenesis

  5. Prediction of Pathological Stage in Patients with Prostate Cancer: A Neuro-Fuzzy Model.

    Directory of Open Access Journals (Sweden)

    Georgina Cosma

    Full Text Available The prediction of cancer staging in prostate cancer is a process for estimating the likelihood that the cancer has spread before treatment is given to the patient. Although important for determining the most suitable treatment and optimal management strategy for patients, staging continues to present significant challenges to clinicians. Clinical test results such as the pre-treatment Prostate-Specific Antigen (PSA level, the biopsy most common tumor pattern (Primary Gleason pattern and the second most common tumor pattern (Secondary Gleason pattern in tissue biopsies, and the clinical T stage can be used by clinicians to predict the pathological stage of cancer. However, not every patient will return abnormal results in all tests. This significantly influences the capacity to effectively predict the stage of prostate cancer. Herein we have developed a neuro-fuzzy computational intelligence model for classifying and predicting the likelihood of a patient having Organ-Confined Disease (OCD or Extra-Prostatic Disease (ED using a prostate cancer patient dataset obtained from The Cancer Genome Atlas (TCGA Research Network. The system input consisted of the following variables: Primary and Secondary Gleason biopsy patterns, PSA levels, age at diagnosis, and clinical T stage. The performance of the neuro-fuzzy system was compared to other computational intelligence based approaches, namely the Artificial Neural Network, Fuzzy C-Means, Support Vector Machine, the Naive Bayes classifiers, and also the AJCC pTNM Staging Nomogram which is commonly used by clinicians. A comparison of the optimal Receiver Operating Characteristic (ROC points that were identified using these approaches, revealed that the neuro-fuzzy system, at its optimal point, returns the largest Area Under the ROC Curve (AUC, with a low number of false positives (FPR = 0.274, TPR = 0.789, AUC = 0.812. The proposed approach is also an improvement over the AJCC pTNM Staging Nomogram (FPR

  6. Quantitative Time-Resolved Fluorescence Imaging of Androgen Receptor and Prostate-Specific Antigen in Prostate Tissue Sections.

    Science.gov (United States)

    Krzyzanowska, Agnieszka; Lippolis, Giuseppe; Helczynski, Leszek; Anand, Aseem; Peltola, Mari; Pettersson, Kim; Lilja, Hans; Bjartell, Anders

    2016-05-01

    Androgen receptor (AR) and prostate-specific antigen (PSA) are expressed in the prostate and are involved in prostate cancer (PCa). The aim of this study was to develop reliable protocols for reproducible quantification of AR and PSA in benign and malignant prostate tissue using time-resolved fluorescence (TRF) imaging techniques. AR and PSA were detected with TRF in tissue microarrays from 91 PCa patients. p63/ alpha-methylacyl-CoA racemase (AMACR) staining on consecutive sections was used to categorize tissue areas as benign or cancerous. Automated image analysis was used to quantify staining intensity. AR intensity was significantly higher in AMACR+ and lower in AMACR- cancer areas as compared with benign epithelium. The PSA intensity was significantly lower in cancer areas, particularly in AMACR- glands. The AR/PSA ratio varied significantly in the AMACR+ tumor cells as compared with benign glands. There was a trend of more rapid disease progression in patients with higher AR/PSA ratios in the AMACR- areas. This study demonstrates the feasibility of developing reproducible protocols for TRF imaging and automated image analysis to study the expression of AR and PSA in benign and malignant prostate. It also highlighted the differences in AR and PSA protein expression within AMACR- and AMACR+ cancer regions. © 2016 The Histochemical Society.

  7. Biological Differences Between Prostate Cancer Cells that Metastasize to Bone Versus Soft Tissue Sites

    National Research Council Canada - National Science Library

    Pienta, Kenneth J

    2004-01-01

    .... Comparisons were made between patients as well as within the same patient. No consistent differences were found between bone and soft tissue sites that could explain the predilection of prostate cancer cells to metastasize to bone...

  8. Prostate-specific antigen density is predictive of outcome in suboptimal prostate seed brachytherapy.

    Science.gov (United States)

    Benzaquen, David; Delouya, Guila; Ménard, Cynthia; Barkati, Maroie; Taussky, Daniel

    In prostate seed brachytherapy, a D 90 of prostate-specific antigen + 2). Univariate and multivariate analyses were performed, adjusting for known prognostic factors such as D 90 and prostate-specific antigen density (PSAD) of ≥0.15 ng/mL/cm 3 , to evaluate their ability to predict BF. Median followup for patients without BF was 72 months (interquartile range 56-96). BF-free recurrence rate at 5 years was 95% and at 8 years 88%. In univariate analysis, PSAD and cancer of the prostate risk assessment score were predictive of BF. On multivariate analysis, none of the factors remained significant. The best prognosis had patients with a low PSAD (<0.15 ng/mL/cm 3 ) and an optimal implant at 30 days after implantation (as defined by D 90  ≥ 130 Gy) compared to patients with both factors unfavorable (p = 0.006). A favorable PSAD was associate with a good prognosis, independently of the D 90 (<130 Gy vs. ≥130 Gy, p = 0.7). Patients with a PSAD of <0.15 ng/mL/cm 3 have little risk of BF, even in the case of a suboptimal implant. These results need to be validated in other patients' cohorts. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  9. Clinical validation of an epigenetic assay to predict negative histopathological results in repeat prostate biopsies.

    Science.gov (United States)

    Partin, Alan W; Van Neste, Leander; Klein, Eric A; Marks, Leonard S; Gee, Jason R; Troyer, Dean A; Rieger-Christ, Kimberly; Jones, J Stephen; Magi-Galluzzi, Cristina; Mangold, Leslie A; Trock, Bruce J; Lance, Raymond S; Bigley, Joseph W; Van Criekinge, Wim; Epstein, Jonathan I

    2014-10-01

    The DOCUMENT multicenter trial in the United States validated the performance of an epigenetic test as an independent predictor of prostate cancer risk to guide decision making for repeat biopsy. Confirming an increased negative predictive value could help avoid unnecessary repeat biopsies. We evaluated the archived, cancer negative prostate biopsy core tissue samples of 350 subjects from a total of 5 urological centers in the United States. All subjects underwent repeat biopsy within 24 months with a negative (controls) or positive (cases) histopathological result. Centralized blinded pathology evaluation of the 2 biopsy series was performed in all available subjects from each site. Biopsies were epigenetically profiled for GSTP1, APC and RASSF1 relative to the ACTB reference gene using quantitative methylation specific polymerase chain reaction. Predetermined analytical marker cutoffs were used to determine assay performance. Multivariate logistic regression was used to evaluate all risk factors. The epigenetic assay resulted in a negative predictive value of 88% (95% CI 85-91). In multivariate models correcting for age, prostate specific antigen, digital rectal examination, first biopsy histopathological characteristics and race the test proved to be the most significant independent predictor of patient outcome (OR 2.69, 95% CI 1.60-4.51). The DOCUMENT study validated that the epigenetic assay was a significant, independent predictor of prostate cancer detection in a repeat biopsy collected an average of 13 months after an initial negative result. Due to its 88% negative predictive value adding this epigenetic assay to other known risk factors may help decrease unnecessary repeat prostate biopsies. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  10. Pharmacodynamic and pharmacokinetic studies and prostatic tissue distribution of fosfomycin tromethamine in bacterial prostatitis or normal rats.

    Science.gov (United States)

    Fan, L; Shang, X; Zhu, J; Ma, B; Zhang, Q

    2018-05-02

    In this study, we assessed the therapeutic effects of fosfomycin tromethamine (FT) in a bacterial prostatitis (BP) rat model. The BP model was induced by Escherichia coli and was demonstrated after 7 days microbiologically and histologically. Then, 25 BP rats selected were randomly divided into five treatment groups: model group, positive group, FT-3 day group, FT-7 day group and FT-14 day group. Ventral lobes of prostate from all animals were removed, and the serum samples were collected at the end of the experiments. Microbiological cultures and histological findings of the prostate samples demonstrated reduced bacterial growth and improved inflammatory responses in FT-treatment groups compared with the model group, indicating that FT against prostatic infection induced by E. coli showed good antibacterial effects. Moreover, plasma pharmacokinetics and prostatic distribution of fosfomycin were studied and compared in BP and normal rats. The concentrations of fosfomycin in samples were analysed by liquid chromatography-tandem mass spectrometry. There were no differences in plasma pharmacokinetic parameters between two groups. But significantly higher penetration of fosfomycin into prostatic tissues was found in BP rats. We therefore suggested that FT had a good therapeutic effect on BP and it might be used in curing masculine reproductive system diseases. © 2018 Blackwell Verlag GmbH.

  11. Automatic registration of multi-modal microscopy images for integrative analysis of prostate tissue sections

    International Nuclear Information System (INIS)

    Lippolis, Giuseppe; Edsjö, Anders; Helczynski, Leszek; Bjartell, Anders; Overgaard, Niels Chr

    2013-01-01

    Prostate cancer is one of the leading causes of cancer related deaths. For diagnosis, predicting the outcome of the disease, and for assessing potential new biomarkers, pathologists and researchers routinely analyze histological samples. Morphological and molecular information may be integrated by aligning microscopic histological images in a multiplex fashion. This process is usually time-consuming and results in intra- and inter-user variability. The aim of this study is to investigate the feasibility of using modern image analysis methods for automated alignment of microscopic images from differently stained adjacent paraffin sections from prostatic tissue specimens. Tissue samples, obtained from biopsy or radical prostatectomy, were sectioned and stained with either hematoxylin & eosin (H&E), immunohistochemistry for p63 and AMACR or Time Resolved Fluorescence (TRF) for androgen receptor (AR). Image pairs were aligned allowing for translation, rotation and scaling. The registration was performed automatically by first detecting landmarks in both images, using the scale invariant image transform (SIFT), followed by the well-known RANSAC protocol for finding point correspondences and finally aligned by Procrustes fit. The Registration results were evaluated using both visual and quantitative criteria as defined in the text. Three experiments were carried out. First, images of consecutive tissue sections stained with H&E and p63/AMACR were successfully aligned in 85 of 88 cases (96.6%). The failures occurred in 3 out of 13 cores with highly aggressive cancer (Gleason score ≥ 8). Second, TRF and H&E image pairs were aligned correctly in 103 out of 106 cases (97%). The third experiment considered the alignment of image pairs with the same staining (H&E) coming from a stack of 4 sections. The success rate for alignment dropped from 93.8% in adjacent sections to 22% for sections furthest away. The proposed method is both reliable and fast and therefore well suited

  12. Impact of obesity on the predictive accuracy of prostate-specific antigen density and prostate-specific antigen in native Korean men undergoing prostate biopsy.

    Science.gov (United States)

    Kim, Jae Heon; Doo, Seung Whan; Yang, Won Jae; Lee, Kwang Woo; Lee, Chang Ho; Song, Yun Seob; Jeon, Yoon Su; Kim, Min Eui; Kwon, Soon-Sun

    2014-10-01

    To evaluate the impact of obesity on the biopsy detection of prostate cancer. We retrospectively reviewed data of 1182 consecutive Korean patients (≥50 years) with serum prostate-specific antigen levels of 3-10 ng/mL who underwent initial extended 12-cores biopsy from September 2009 to March 2013. Patients who took medications that were likely to influence the prostate-specific antigen level were excluded. Receiver operating characteristic curves were plotted for prostate-specific antigen and prostate-specific antigen density predicting cancer status among non-obese and obese men. A total of 1062 patients (mean age 67.1 years) were enrolled in the analysis. A total of 230 men (21.7%) had a positive biopsy. In the overall study sample, the area under the receiver operator characteristic curve of serum prostate-specific antigen for predicting prostate cancer on biopsy were 0.584 and 0.633 for non-obese and obese men, respectively (P = 0.234). However, the area under the curve for prostate-specific antigen density in predicting cancer status showed a significant difference (non-obese 0.696, obese 0.784; P = 0.017). There seems to be a significant difference in the ability of prostate-specific antigen density to predict biopsy results between non-obese and obese men. Obesity positively influenced the overall ability of prostate-specific antigen density to predict prostate cancer. © 2014 The Japanese Urological Association.

  13. Quantitative RT-PCR analysis of estrogen receptor gene expression in laser microdissected prostate cancer tissue.

    Science.gov (United States)

    Walton, Thomas J; Li, Geng; McCulloch, Thomas A; Seth, Rashmi; Powe, Desmond G; Bishop, Michael C; Rees, Robert C

    2009-06-01

    Real-time quantitative RT-PCR analysis of laser microdissected tissue is considered the most accurate technique for determining tissue gene expression. The discovery of estrogen receptor beta (ERbeta) has focussed renewed interest on the role of estrogen receptors in prostate cancer, yet few studies have utilized the technique to analyze estrogen receptor gene expression in prostate cancer. Fresh tissue was obtained from 11 radical prostatectomy specimens and from 6 patients with benign prostate hyperplasia. Pure populations of benign and malignant prostate epithelium were laser microdissected, followed by RNA isolation and electrophoresis. Quantitative RT-PCR was performed using primers for androgen receptor (AR), estrogen receptor beta (ERbeta), estrogen receptor alpha (ERalpha), progesterone receptor (PGR) and prostate specific antigen (PSA), with normalization to two housekeeping genes. Differences in gene expression were analyzed using the Mann-Whitney U-test. Correlation coefficients were analyzed using Spearman's test. Significant positive correlations were seen when AR and AR-dependent PSA, and ERalpha and ERalpha-dependent PGR were compared, indicating a representative population of RNA transcripts. ERbeta gene expression was significantly over-expressed in the cancer group compared with benign controls (P cancer group (P prostate cancer specimens. In concert with recent studies the findings suggest differential production of ERbeta splice variants, which may play important roles in the genesis of prostate cancer. (c) 2009 Wiley-Liss, Inc.

  14. Pretreatment tables predicting pathologic stage of locally advanced prostate cancer.

    Science.gov (United States)

    Joniau, Steven; Spahn, Martin; Briganti, Alberto; Gandaglia, Giorgio; Tombal, Bertrand; Tosco, Lorenzo; Marchioro, Giansilvio; Hsu, Chao-Yu; Walz, Jochen; Kneitz, Burkhard; Bader, Pia; Frohneberg, Detlef; Tizzani, Alessandro; Graefen, Markus; van Cangh, Paul; Karnes, R Jeffrey; Montorsi, Francesco; van Poppel, Hein; Gontero, Paolo

    2015-02-01

    Pretreatment tables for the prediction of pathologic stage have been published and validated for localized prostate cancer (PCa). No such tables are available for locally advanced (cT3a) PCa. To construct tables predicting pathologic outcome after radical prostatectomy (RP) for patients with cT3a PCa with the aim to help guide treatment decisions in clinical practice. This was a multicenter retrospective cohort study including 759 consecutive patients with cT3a PCa treated with RP between 1987 and 2010. Retropubic RP and pelvic lymphadenectomy. Patients were divided into pretreatment prostate-specific antigen (PSA) and biopsy Gleason score (GS) subgroups. These parameters were used to construct tables predicting pathologic outcome and the presence of positive lymph nodes (LNs) after RP for cT3a PCa using ordinal logistic regression. In the model predicting pathologic outcome, the main effects of biopsy GS and pretreatment PSA were significant. A higher GS and/or higher PSA level was associated with a more unfavorable pathologic outcome. The validation procedure, using a repeated split-sample method, showed good predictive ability. Regression analysis also showed an increasing probability of positive LNs with increasing PSA levels and/or higher GS. Limitations of the study are the retrospective design and the long study period. These novel tables predict pathologic stage after RP for patients with cT3a PCa based on pretreatment PSA level and biopsy GS. They can be used to guide decision making in men with locally advanced PCa. Our study might provide physicians with a useful tool to predict pathologic stage in locally advanced prostate cancer that might help select patients who may need multimodal treatment. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  15. Predictive value of different prostate-specific antigen-based markers in men with baseline total prostate-specific antigen <2.0 ng/mL.

    Science.gov (United States)

    Fujizuka, Yuji; Ito, Kazuto; Oki, Ryo; Suzuki, Rie; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Suzuki, Kazuhiro

    2017-08-01

    To investigate the predictive value of various molecular forms of prostate-specific antigen in men with baseline prostate-specific antigen baseline prostate-specific antigen level baseline prostate-specific antigen- and age-adjusted men who did not develop prostate cancer. Serum prostate-specific antigen, free prostate-specific antigen, and [-2] proenzyme prostate-specific antigen were measured at baseline and last screening visit. The predictive impact of baseline prostate-specific antigen- and [-2] proenzyme prostate-specific antigen-related indices on developing prostate cancer was investigated. The predictive impact of those indices at last screening visit and velocities from baseline to final screening on tumor aggressiveness were also investigated. The baseline free to total prostate-specific antigen ratio was a significant predictor of prostate cancer development. The odds ratio was 6.08 in the lowest quintile baseline free to total prostate-specific antigen ratio subgroup. No serum indices at diagnosis were associated with tumor aggressiveness. The Prostate Health Index velocity and [-2] proenzyme prostate-specific antigen/free prostate-specific antigen velocity significantly increased in patients with higher risk D'Amico risk groups and higher Gleason scores. Free to total prostate-specific antigen ratio in men with low baseline prostate-specific antigen levels seems to predict the risk of developing prostate cancer, and it could be useful for a more effective individualized screening system. Longitudinal changes in [-2] proenzyme prostate-specific antigen-related indices seem to correlate with tumor aggressiveness, and they could be used as prognostic tool before treatment and during active surveillance. © 2017 The Japanese Urological Association.

  16. Age and total and free prostate-specific antigen levels for predicting prostate volume in patients with benign prostatic hyperplasia.

    Science.gov (United States)

    Coban, Soner; Doluoglu, Omer Gokhan; Keles, Ibrahim; Demirci, Hakan; Turkoglu, Ali Riza; Guzelsoy, Muhammet; Karalar, Mustafa; Demirbas, Murat

    2016-06-01

    To investigate the predictive values of free prostate-specific antigen (fPSA), total PSA (tPSA) and age on the prostate volume. The data of 2148 patients with lower urinary tract symptoms were analyzed retrospectively. The patients who had transrectal ultrasonography guided 10 core biopsies owing to the findings obtained on digital rectal examination and presence of high PSA levels (PSA = 2.5-10 ng/dl), and proven to have BPH histopathologically were included in the study. Age, tPSA, fPSA and the prostate volumes (PV) of the patients were noted. One thousand patients that fulfilled the inclusion criteria were included in the study. The PV of the patients were significantly correlated with age, tPSA and fPSA (p < 0.001 and r = 0.307, p < 0.001 and r = 0.382, p < 0.001 and r = 0.296, respectively). On linear regression model, fPSA was found as a stronger predictive for PV (AUC = 0.75, p < 0.001) when compared to age (AUC = 0.64, p < 0.001), and tPSA (AUC = 0.69, p = 0.013). Although tPSA is an important prognostic factor for predicting PV, the predictive value of fPSA is higher. PV can easily be predicted by using age, and serum tPSA and fPSA levels.

  17. Molecular Markers for Prostate Cancer in Formalin-Fixed Paraffin-Embedded Tissues

    Directory of Open Access Journals (Sweden)

    Tamara Sequeiros

    2013-01-01

    Full Text Available Prostate cancer (PCa is the most frequently diagnosed type of cancer in developed countries. The decisive method of diagnosis is based on the results of biopsies, morphologically evaluated to determine the presence or absence of cancer. Although this approach leads to a confident diagnosis in most cases, it can be improved by using the molecular markers present in the tissue. Both miRNAs and proteins are considered excellent candidates for biomarkers in formalin-fixed paraffin-embedded (FFPE tissues, due to their stability over long periods of time. In the last few years, a concerted effort has been made to develop the necessary tools for their reliable measurement in these types of samples. Furthermore, the use of these kinds of markers may also help in establishing tumor grade and aggressiveness, as well as predicting the possible outcomes in each particular case for the different treatments available. This would aid clinicians in the decision-making process. In this review, we attempt to summarize and discuss the potential use of microRNA and protein profiles in FFPE tissue samples as markers to better predict PCa diagnosis, progression, and response to therapy.

  18. Prostatitis

    Science.gov (United States)

    Prostatitis Overview Prostatitis is swelling and inflammation of the prostate gland, a walnut-sized gland situated directly below the bladder in ... produces fluid (semen) that nourishes and transports sperm. Prostatitis often causes painful or difficult urination. Other symptoms ...

  19. Photodynamic therapy in prostate cancer: optical dosimetry and response of normal tissue

    Science.gov (United States)

    Chen, Qun; Shetty, Sugandh D.; Heads, Larry; Bolin, Frank; Wilson, Brian C.; Patterson, Michael S.; Sirls, Larry T., II; Schultz, Daniel; Cerny, Joseph C.; Hetzel, Fred W.

    1993-06-01

    The present study explores the possibility of utilizing photodynamic therapy (PDT) in treating localized prostate carcinoma. Optical properties of ex vivo human prostatectomy specimens, and in vivo and ex vivo dog prostate glands were studied. The size of the PDT induced lesion in dog prostate was pathologically evaluated as a biological endpoint. The data indicate that the human normal and carcinoma prostate tissues have similar optical properties. The average effective attenuation depth is less in vivo than that of ex vivo. The PDT treatment generated a lesion size of up to 16 mm in diameter. The data suggest that PDT is a promising modality in prostate cancer treatment. Multiple fiber system may be required for clinical treatment.

  20. Elemental concentration analysis in prostate tissues using total reflection X-ray fluorescence

    International Nuclear Information System (INIS)

    Leitão, R.G.; Palumbo, A.; Souza, P.A.V.R.; Pereira, G.R.; Canellas, C.G.L.; Anjos, M.J.; Nasciutti, L.E.; Lopes, R.T.

    2014-01-01

    Prostate cancer (PCa) currently represents the second most prevalent malignant neoplasia in men, representing 21% of all cancer cases. Benign Prostate Hyperplasia (BPH) is an illness prevailing in men above the age of 50, close to 90% after the age of 80. The prostate presents a high zinc concentration, about 10-fold higher than any other body tissue. In this work, samples of human prostate tissues with cancer, BPH and normal tissue were analyzed utilizing total reflection X-ray fluorescence spectroscopy using synchrotron radiation technique (SR-TXRF) to investigate the differences in the elemental concentrations in these tissues. SR-TXRF analyses were performed at the X-ray fluorescence beamline at Brazilian National Synchrotron Light Laboratory (LNLS), in Campinas, São Paulo. It was possible to determine the concentrations of the following elements: P, S, K, Ca, Fe, Cu, Zn and Rb. By using Mann–Whitney U test it was observed that almost all elements presented concentrations with significant differences (α=0.05) between the groups studied. - Highlights: ► Prostate cancer is the most frequently diagnosed form of cancer in men. ► Intracellular Zn is correlated with proliferation, differentiation, or apoptosis. ► The prostate gland accumulate high concentration of Zn. ► SR-TXRF is a technique widely used in the analysis of low concentration in samples

  1. Radiogenomics: predicting clinical normal tissue radiosensitivity

    DEFF Research Database (Denmark)

    Alsner, Jan

    2006-01-01

    Studies on the genetic basis of normal tissue radiosensitivity, or  'radiogenomics', aims at predicting clinical radiosensitivity and optimize treatment from individual genetic profiles. Several studies have now reported links between variations in certain genes related to the biological response...... to radiation injury and risk of normal tissue morbidity in cancer patients treated with radiotherapy. However, after these initial association studies including few genes, we are still far from being able to predict clinical radiosensitivity on an individual level. Recent data from our own studies on risk...

  2. The zinc distribution in prostate tissues using X-ray microfluorescence with synchrotron radiation

    International Nuclear Information System (INIS)

    Leitao, Roberta G.; Anjos, Marcelino J.; Canellas, Catarine G.L.; Pereira, Marcelo O.; Pereira, Gabriela R.; Lopes, Ricardo T.

    2009-01-01

    Many elements play an essential role in a number of biological processes as activators or inhibitors of cellular and enzymatic activity. The topographic and quantitative elemental analysis of pathologically changed tissues may shed some new light on processes leading to the degeneration of cells in case of selected diseases. Zinc concentration in a prostate gland is much higher than that in other human tissues. The high concentration of zinc in the prostate suggests that zinc may play a role in prostate health. The aim of this work was to study the elemental distribution for Zinc in prostate tissues from patterns of relative fluorescence intensities. The measurements were performed in standard geometry of 45 deg incidence, exciting with a white beam and using a conventional system collimation orthogonal slits) in the XRF beam line at the Synchrotron Light National Laboratory (Campinas, Brazil). The prostate glands were cut into pieces (slice) with thickness of 0.5 mm. The results showed the zinc distribution was not uniform for different zones of the prostate analyzed. (author)

  3. Inter- and Intra-Observer Variability in Prostate Definition With Tissue Harmonic and Brightness Mode Imaging

    International Nuclear Information System (INIS)

    Sandhu, Gurpreet Kaur; Dunscombe, Peter; Meyer, Tyler; Pavamani, Simon; Khan, Rao

    2012-01-01

    Purpose: The objective of this study was to compare the relative utility of tissue harmonic (H) and brightness (B) transrectal ultrasound (TRUS) images of the prostate by studying interobserver and intraobserver variation in prostate delineation. Methods and Materials: Ten patients with early-stage disease were randomly selected. TRUS images of prostates were acquired using B and H modes. The prostates on all images were contoured by an experienced radiation oncologist (RO) and five equally trained observers. The observers were blinded to information regarding patient and imaging mode. The volumes of prostate glands and areas of midgland slices were calculated. Volumes contoured were compared among the observers and between observer group and RO. Contours on one patient were repeated five times by four observers to evaluate the intraobserver variability. Results: A one-sample Student t-test showed the volumes outlined by five observers are in agreement (p > 0.05) with the RO. Paired Student t-test showed prostate volumes (p = 0.008) and midgland areas (p = 0.006) with H mode were significantly smaller than that with B mode. Two-factor analysis of variances showed significant interobserver variability (p < 0.001) in prostate volumes and areas. Inter- and intraobserver consistency was quantified as the standard deviation of mean volumes and areas, and concordance indices. It was found that for small glands (≤35 cc) H mode provided greater interobserver consistency; however, for large glands (≥35 cc), B mode provided more consistent estimates. Conclusions: H mode provided superior inter- and intraobserver agreement in prostate volume definition for small to medium prostates. In large glands, H mode does not exhibit any additional advantage. Although harmonic imaging has not proven advantageous for all cases, its utilization seems to be judicious for small prostates.

  4. A method for tissue extraction and determination of prostate concentrations of endogenous androgens by radioimmunoassay

    International Nuclear Information System (INIS)

    Albert, J.; Geller, J.; Geller, S.; Lopez, D.

    1976-01-01

    A method for simultaneously determining concentrations of major androgens in prostate has been developed. Extraction techniques used to isolate the androgens from minced tissue include homogenization with high-speed blades in Delsal's solvent mixture, adsorption to silica gel, followed by column and one thin-layer chromatography (TLC). Radioimmunoassays (RIA) of small aliquots of TLC eluates are used to quantitate picogram amounts of 5α-dihydrotestosterone (DHT) and 5α-androstanediols (Diol) and to estimate testosterone (T) and androstenedione (Ad). Contamination of blanks was reduced to RIA sensitivity limits primarily by treatment of glassware in a self-cleaning oven. The specificity of the method for each androgen was established by TLC separations of known prostate metabolites, antisera specificities, and parallelism of sample aliquots to androgen RIA standards. The overall precision, in terms of coefficients of variation, was 21% for DHT and 24% for Diol. T and Ad could not be measured with acceptable precision because their very low concentrations in prostate (<=0.5 ng/g tissue) were less than RIA sensitivity limits. Accuracy studies indicated recoveries ranging from 96% for Diol to 121% for DHT. In human benign hypertrophic prostate tissue, DHT averaged 153 ng/g soluble protein (5.8 ng/g tissue) which was 17 times higher than values obtained in human spleen and kidney; Diol in prostate showed no consistent differences from values noted in kidney or spleen

  5. Elemental concentration analysis in PCa, BPH and normal prostate tissues using SR-TXRF

    International Nuclear Information System (INIS)

    Leitao, Roberta G.; Anjos, Marcelino J.; Canellas, Catarine G.L.; Lopes, Ricardo T.

    2009-01-01

    Prostate cancer (PCa) is one of the main causes of illness and death all over the world. In Brazil, prostate cancer currently represents the second most prevalent malignant neoplasia in men, representing 21% of all cancer cases. Benign Prostate Hyperplasia (BPH) is an illness prevailing in men above the age of 50, close to 90% after the age of 80. The prostate presents a high zinc concentration, about 10-fold higher than any other body tissue. In this work, samples of human prostate tissues with cancer (PCa), BPH and normal tissue were analyzed utilizing the total reflection X-ray fluorescence spectroscopy using synchrotron radiation technique (SRTXRF) to investigate the differences in the elemental concentrations in these tissues. SR-TXRF analyses were performed at the X-Ray fluorescence beamline at Brazilian National Synchrotron Light Laboratory (LNLS), in Campinas, Sao Paulo. It was possible to determine the concentrations of the following elements: P, S, K, Ca, Fe, Cu, Zn, Br and Rb. By using Mann-Whitney U test it was observed that almost all elements presented concentrations with significant differences α = 0.05) between the groups studied. The elements and groups were: S, K, Ca, Fe, Zn, Br and Rb (PCa X Normal); S, Fe, Zn and Br (PCa X BPH); K, Ca, Fe, Zn, Br and Rb (BPH X Normal). (author)

  6. Protease Expression Levels in Prostate Cancer Tissue Can Explain Prostate Cancer-Associated Seminal Biomarkers—An Explorative Concept Study

    Directory of Open Access Journals (Sweden)

    Jochen Neuhaus

    2017-05-01

    Full Text Available Previously, we described prostate cancer (PCa detection (83% sensitivity; 67% specificity in seminal plasma by CE-MS/MS. Moreover, advanced disease was distinguished from organ-confined tumors with 80% sensitivity and 82% specificity. The discovered biomarkers were naturally occurring fragments of larger seminal proteins, predominantly semenogelin 1 and 2, representing endpoints of the ejaculate liquefaction. Here we identified proteases putatively involved in PCa specific protein cleavage, and examined gene expression and tissue protein levels, jointly with cell localization in normal prostate (nP, benign prostate hyperplasia (BPH, seminal vesicles and PCa using qPCR, Western blotting and confocal laser scanning microscopy. We found differential gene expression of chymase (CMA1, matrix metalloproteinases (MMP3, MMP7, and upregulation of MMP14 and tissue inhibitors (TIMP1 and TIMP2 in BPH. In contrast tissue protein levels of MMP14 were downregulated in PCa. MMP3/TIMP1 and MMP7/TIMP1 ratios were decreased in BPH. In seminal vesicles, we found low-level expression of most proteases and, interestingly, we also detected TIMP1 and low levels of TIMP2. We conclude that MMP3 and MMP7 activity is different in PCa compared to BPH due to fine regulation by their inhibitor TIMP1. Our findings support the concept of seminal plasma biomarkers as non-invasive tool for PCa detection and risk stratification.

  7. Protease Expression Levels in Prostate Cancer Tissue Can Explain Prostate Cancer-Associated Seminal Biomarkers-An Explorative Concept Study.

    Science.gov (United States)

    Neuhaus, Jochen; Schiffer, Eric; Mannello, Ferdinando; Horn, Lars-Christian; Ganzer, Roman; Stolzenburg, Jens-Uwe

    2017-05-04

    Previously, we described prostate cancer (PCa) detection (83% sensitivity; 67% specificity) in seminal plasma by CE-MS/MS. Moreover, advanced disease was distinguished from organ-confined tumors with 80% sensitivity and 82% specificity. The discovered biomarkers were naturally occurring fragments of larger seminal proteins, predominantly semenogelin 1 and 2, representing endpoints of the ejaculate liquefaction. Here we identified proteases putatively involved in PCa specific protein cleavage, and examined gene expression and tissue protein levels, jointly with cell localization in normal prostate (nP), benign prostate hyperplasia (BPH), seminal vesicles and PCa using qPCR, Western blotting and confocal laser scanning microscopy. We found differential gene expression of chymase (CMA1), matrix metalloproteinases (MMP3, MMP7), and upregulation of MMP14 and tissue inhibitors (TIMP1 and TIMP2) in BPH. In contrast tissue protein levels of MMP14 were downregulated in PCa. MMP3/TIMP1 and MMP7/TIMP1 ratios were decreased in BPH. In seminal vesicles, we found low-level expression of most proteases and, interestingly, we also detected TIMP1 and low levels of TIMP2. We conclude that MMP3 and MMP7 activity is different in PCa compared to BPH due to fine regulation by their inhibitor TIMP1. Our findings support the concept of seminal plasma biomarkers as non-invasive tool for PCa detection and risk stratification.

  8. Clonal Evaluation of Prostate Cancer by ERG/SPINK1 Status to Improve Prognosis Prediction

    Science.gov (United States)

    2017-12-01

    19 NIH Exploiting drivers of androgen receptor signaling negative prostate cancer for precision medicine Goal(s): Identify novel potential drivers...AWARD NUMBER: W81XWH-14-1-0466 TITLE: Clonal evaluation of prostate cancer by ERG/SPINK1 status to improve prognosis prediction PRINCIPAL...Sept 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Clonal Evaluation of Prostate Cancer by ERG/SPINK1 Status to Improve Prognosis Prediction 5b

  9. An evaluation of serum and tissue bound immunoglobulins in prostatic diseases.

    Directory of Open Access Journals (Sweden)

    Gahankari D

    1993-04-01

    Full Text Available In forty-four patients with different prostatic lesions serum immunoglobulins and tissue deposited immunoglobulins were studied by single radial immunodiffusion technique, and direct immunofluorescence and immunoperoxidase (PAP methods respectively. Serum IgM levels were found reduced only in patients with prostatic carcinomas (80% of cases as compared to controls. Serum IgA levels showed stage dependence in prostatic carcinoma being more raised in advanced malignancy (stage C and D than in localized ones (stage B. Localization of immunoglobulins particularly IgM, was characteristically found in stroma and lumen along with intracellular localization in prostatic carcinoma; while normal and benign lesions of prostate only showed characteristic ′necklace′ pattern. Also the intensity of deposits of immunoglobulins in poorly differentiated prostatic carcinomas was markedly low as compared to well differentiated carcinomas indicating lowered local immunological response in former. In prostatitis, IgA was also found localized in lumen indicating the immunological defence against infection by secretory antibody (IgA.

  10. Combinations of elevated tissue miRNA-17-92 cluster expression and serum prostate-specific antigen as potential diagnostic biomarkers for prostate cancer.

    Science.gov (United States)

    Feng, Sujuan; Qian, Xiaosong; Li, Han; Zhang, Xiaodong

    2017-12-01

    The aim of the present study was to investigate the effectiveness of the miR-17-92 cluster as a disease progression marker in prostate cancer (PCa). Reverse transcription-quantitative polymerase chain reaction analysis was used to detect the microRNA (miR)-17-92 cluster expression levels in tissues from patients with PCa or benign prostatic hyperplasia (BPH), in addition to in PCa and BPH cell lines. Spearman correlation was used for comparison and estimation of correlations between miRNA expression levels and clinicopathological characteristics such as the Gleason score and prostate-specific antigen (PSA). Receiver operating curve (ROC) analysis was performed for evaluation of specificity and sensitivity of miR-17-92 cluster expression levels for discriminating patients with PCa from patients with BPH. Kaplan-Meier analysis was plotted to investigate the predictive potential of miR-17-92 cluster for PCa biochemical recurrence. Expression of the majority of miRNAs in the miR-17-92 cluster was identified to be significantly increased in PCa tissues and cell lines. Bivariate correlation analysis indicated that the high expression of unregulated miRNAs was positively correlated with Gleason grade, but had no significant association with PSA. ROC curves demonstrated that high expression of miR-17-92 cluster predicted a higher diagnostic accuracy compared with PSA. Improved discriminating quotients were observed when combinations of unregulated miRNAs with PSA were used. Survival analysis confirmed a high combined miRNA score of miR-17-92 cluster was associated with shorter biochemical recurrence interval. miR-17-92 cluster could be a potential diagnostic and prognostic biomarker for PCa, and the combination of the miR-17-92 cluster and serum PSA may enhance the accuracy for diagnosis of PCa.

  11. Thioredoxin 1 in Prostate Tissue Is Associated with Gleason Score, Erythrocyte Antioxidant Enzyme Activity, and Dietary Antioxidants

    Directory of Open Access Journals (Sweden)

    Terrence M. Vance

    2015-01-01

    Full Text Available Background. Prostate cancer is the most common noncutaneous cancer and second leading cause of cancer-related mortality in men in the US. Growing evidence suggests that oxidative stress is involved in prostate cancer. Methods. In this study, thioredoxin 1 (Trx 1, an enzyme and subcellular indicator of redox status, was measured in prostate biopsy tissue from 55 men from the North Carolina-Louisiana Prostate Cancer Project. A pathologist blindly scored levels of Trx 1. The association between Trx 1 and the Gleason score, erythrocyte antioxidant enzyme activity, and dietary antioxidant intake was determined using Fisher’s exact test. Results. Trx 1 levels in benign prostate tissue in men with incident prostate cancer were positively associated with the Gleason score (P=0.01 and inversely associated with dietary antioxidant intake (P=0.03. In prostate cancer tissue, Trx 1 levels were associated with erythrocyte glutathione peroxidase activity (P=0.01. No association was found for other erythrocyte enzymes. Greater Gleason score of malignant tissue corresponds to a greater difference in Trx 1 levels between malignant and benign tissue (P=0.04. Conclusion. These results suggest that the redox status of prostate tissue is associated with prostate cancer grade and both endogenous and exogenous antioxidants.

  12. Finite element simulation of interactions between pelvic organs: predictive model of the prostate motion in the context of radiotherapy.

    Science.gov (United States)

    Boubaker, Mohamed Bader; Haboussi, Mohamed; Ganghoffer, Jean-François; Aletti, Pierre

    2009-08-25

    The setting up of predictive models of the pelvic organ motion and deformation may prove an efficient tool in the framework of prostate cancer radiotherapy, in order to deliver doses more accurately and efficiently to the clinical target volume (CTV). A finite element (FE) model of the prostate, rectum and bladder motion has been developed, investigating more specifically the influence of the rectum and bladder repletions on the gland motion. The required organ geometries are obtained after processing the computed tomography (CT) images, using specific softwares. Due to their structural characteristics, a 3D shell discretization is adopted for the rectum and the bladder, whereas a volume discretization is adopted for the prostate. As for the mechanical behavior modelling, first order Ogden hyperelastic constitutive laws for both the rectum and bladder are identified. The prostate is comparatively considered as more rigid and is accordingly modelled as an elastic tissue undergoing small strains. A FE model is then created, accounting for boundary and contact conditions, internal and applied loadings being selected as close as possible to available anatomic data. The order of magnitude of the prostate motion predicted by the FE simulations is similar to the measurements done on a deceased person, accounting for the delineation errors, with a relative error around 8%. Differences are essentially due to uncertainties in the constitutive parameters, pointing towards the need for the setting up of direct measurement of the organs mechanical behavior.

  13. Loss of high-molecular-weight cytokeratin antigenicity in prostate tissue obtained by transurethral resections

    DEFF Research Database (Denmark)

    Multhaupt, H A; Fessler, J N; Warhol, M J

    2000-01-01

    could be restored in these specimens by antigen retrieval in a low pH citrate buffer using a microwave heat technique. Keratin staining in needle biopsies and total prostatectomies was unaffected. CONCLUSION: In summary, our results indicate the technique of transurethral resection results in a specific......OBJECTIVE: Staining of prostatic basal cells for the expression of high-molecular-weight cytokeratin has been suggested as a way of distinguishing benign from malignant prostate glands. We evaluated the utility of high-molecular-weight cytokeratin in the diagnosis of malignancy in prostate...... specimens obtained in various ways. DESIGN: Prostate tissues obtained from needle biopsies, transurethral resections, and total prostatectomies were immunostained with monoclonal antibody 34betaE12, an antibody directed against high-molecular-weight cytokeratins. RESULTS: Antiserum to high...

  14. Hypoxic Prostate/Muscle PO{sub 2} Ratio Predicts for Outcome in Patients With Localized Prostate Cancer: Long-Term Results

    Energy Technology Data Exchange (ETDEWEB)

    Turaka, Aruna [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA (United States); Buyyounouski, Mark K., E-mail: mark.buyyounouski@fccc.edu [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA (United States); Hanlon, Alexandra L. [School of Nursing, University of Pennsylvania, Philadelphia, PA (United States); Horwitz, Eric M. [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA (United States); Greenberg, Richard E. [Department of Surgery, Fox Chase Cancer Center, Philadelphia, PA (United States); Movsas, Benjamin [Department of Radiation Oncology, Henry Ford Hospital, Detroit, MI (United States)

    2012-03-01

    Purpose: To correlate tumor oxygenation status with long-term biochemical outcome after prostate brachytherapy. Methods and Materials: Custom-made Eppendorf PO{sub 2} microelectrodes were used to obtain PO{sub 2} measurements from the prostate (P), focused on positive biopsy locations, and normal muscle tissue (M), as a control. A total of 11,516 measurements were obtained in 57 men with localized prostate cancer immediately before prostate brachytherapy was given. The Eppendorf histograms provided the median PO{sub 2}, mean PO{sub 2}, and % <5 mm Hg or <10 mm Hg. Biochemical failure (BF) was defined using both the former American Society of Therapeutic Radiation Oncology (ASTRO) (three consecutive raises) and the current Phoenix (prostate-specific antigen nadir + 2 ng/mL) definitions. A Cox proportional hazards regression model evaluated the influence of hypoxia using the P/M mean PO{sub 2} ratio on BF. Results: With a median follow-up time of 8 years, 12 men had ASTRO BF and 8 had Phoenix BF. On multivariate analysis, P/M PO{sub 2} ratio <0.10 emerged as the only significant predictor of ASTRO BF (p = 0.043). Hormonal therapy (p = 0.015) and P/M PO{sub 2} ratio <0.10 (p = 0.046) emerged as the only independent predictors of the Phoenix BF. Kaplan-Meier freedom from BF for P/M ratio <0.10 vs. {>=}0.10 at 8 years for ASTRO BF was 46% vs. 78% (p = 0.03) and for the Phoenix BF was 66% vs. 83% (p = 0.02). Conclusions: Hypoxia in prostate cancer (low mean P/M PO{sub 2} ratio) significantly predicts for poor long-term biochemical outcome, suggesting that novel hypoxic strategies should be investigated.

  15. Resonance sensor measurements of stiffness variations in prostate tissue in vitro--a weighted tissue proportion model.

    Science.gov (United States)

    Jalkanen, Ville; Andersson, Britt M; Bergh, Anders; Ljungberg, Börje; Lindahl, Olof A

    2006-12-01

    Prostate cancer is the most common type of cancer in men in Europe and the US. The methods to detect prostate cancer are still precarious and new techniques are needed. A piezoelectric transducer element in a feedback system is set to vibrate with its resonance frequency. When the sensor element contacts an object a change in the resonance frequency is observed, and this feature has been utilized in sensor systems to describe physical properties of different objects. For medical applications it has been used to measure stiffness variations due to various patho-physiological conditions. In this study the sensor's ability to measure the stiffness of prostate tissue, from two excised prostatectomy specimens in vitro, was analysed. The specimens were also subjected to morphometric measurements, and the sensor parameter was compared with the morphology of the tissue with linear regression. In the probe impression interval 0.5-1.7 mm, the maximum R(2) > or = 0.60 (p sensor was pressed, the greater, i.e., deeper, volume it sensed. Tissue sections deeper in the tissue were assigned a lower mathematical weighting than sections closer to the sensor probe. It is concluded that cancer increases the measured stiffness as compared with healthy glandular tissue, but areas with predominantly stroma or many stones could be more difficult to differ from cancer.

  16. Prostate cancer prediction using the random forest algorithm that takes into account transrectal ultrasound findings, age, and serum levels of prostate-specific antigen.

    Science.gov (United States)

    Xiao, Li-Hong; Chen, Pei-Ran; Gou, Zhong-Ping; Li, Yong-Zhong; Li, Mei; Xiang, Liang-Cheng; Feng, Ping

    2017-01-01

    The aim of this study is to evaluate the ability of the random forest algorithm that combines data on transrectal ultrasound findings, age, and serum levels of prostate-specific antigen to predict prostate carcinoma. Clinico-demographic data were analyzed for 941 patients with prostate diseases treated at our hospital, including age, serum prostate-specific antigen levels, transrectal ultrasound findings, and pathology diagnosis based on ultrasound-guided needle biopsy of the prostate. These data were compared between patients with and without prostate cancer using the Chi-square test, and then entered into the random forest model to predict diagnosis. Patients with and without prostate cancer differed significantly in age and serum prostate-specific antigen levels (P prostate-specific antigen and ultrasound predicted prostate cancer with an accuracy of 83.10%, sensitivity of 65.64%, and specificity of 93.83%. Positive predictive value was 86.72%, and negative predictive value was 81.64%. By integrating age, prostate-specific antigen levels and transrectal ultrasound findings, the random forest algorithm shows better diagnostic performance for prostate cancer than either diagnostic indicator on its own. This algorithm may help improve diagnosis of the disease by identifying patients at high risk for biopsy.

  17. Prostate cancer prediction using the random forest algorithm that takes into account transrectal ultrasound findings, age, and serum levels of prostate-specific antigen

    Directory of Open Access Journals (Sweden)

    Li-Hong Xiao

    2017-01-01

    Full Text Available The aim of this study is to evaluate the ability of the random forest algorithm that combines data on transrectal ultrasound findings, age, and serum levels of prostate-specific antigen to predict prostate carcinoma. Clinico-demographic data were analyzed for 941 patients with prostate diseases treated at our hospital, including age, serum prostate-specific antigen levels, transrectal ultrasound findings, and pathology diagnosis based on ultrasound-guided needle biopsy of the prostate. These data were compared between patients with and without prostate cancer using the Chi-square test, and then entered into the random forest model to predict diagnosis. Patients with and without prostate cancer differed significantly in age and serum prostate-specific antigen levels (P < 0.001, as well as in all transrectal ultrasound characteristics (P < 0.05 except uneven echo (P = 0.609. The random forest model based on age, prostate-specific antigen and ultrasound predicted prostate cancer with an accuracy of 83.10%, sensitivity of 65.64%, and specificity of 93.83%. Positive predictive value was 86.72%, and negative predictive value was 81.64%. By integrating age, prostate-specific antigen levels and transrectal ultrasound findings, the random forest algorithm shows better diagnostic performance for prostate cancer than either diagnostic indicator on its own. This algorithm may help improve diagnosis of the disease by identifying patients at high risk for biopsy.

  18. Inter- and intra-observer variability in prostate definition with tissue harmonic and brightness mode imaging.

    Science.gov (United States)

    Sandhu, Gurpreet Kaur; Dunscombe, Peter; Meyer, Tyler; Pavamani, Simon; Khan, Rao

    2012-01-01

    The objective of this study was to compare the relative utility of tissue harmonic (H) and brightness (B) transrectal ultrasound (TRUS) images of the prostate by studying interobserver and intraobserver variation in prostate delineation. Ten patients with early-stage disease were randomly selected. TRUS images of prostates were acquired using B and H modes. The prostates on all images were contoured by an experienced radiation oncologist (RO) and five equally trained observers. The observers were blinded to information regarding patient and imaging mode. The volumes of prostate glands and areas of midgland slices were calculated. Volumes contoured were compared among the observers and between observer group and RO. Contours on one patient were repeated five times by four observers to evaluate the intraobserver variability. A one-sample Student t-test showed the volumes outlined by five observers are in agreement (p > 0.05) with the RO. Paired Student t-test showed prostate volumes (p = 0.008) and midgland areas (p = 0.006) with H mode were significantly smaller than that with B mode. Two-factor analysis of variances showed significant interobserver variability (p standard deviation of mean volumes and areas, and concordance indices. It was found that for small glands (≤35 cc) H mode provided greater interobserver consistency; however, for large glands (≥35 cc), B mode provided more consistent estimates. H mode provided superior inter- and intraobserver agreement in prostate volume definition for small to medium prostates. In large glands, H mode does not exhibit any additional advantage. Although harmonic imaging has not proven advantageous for all cases, its utilization seems to be judicious for small prostates. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  19. Online Image-based Monitoring of Soft-tissue Displacements for Radiation Therapy of the Prostate

    International Nuclear Information System (INIS)

    Schlosser, Jeffrey; Salisbury, Kenneth; Hristov, Dimitre

    2012-01-01

    Purpose: Emerging prolonged, hypofractionated radiotherapy regimens rely on high-dose conformality to minimize toxicity and thus can benefit from image guidance systems that continuously monitor target position during beam delivery. To address this need we previously developed, as a potential add-on device for existing linear accelerators, a novel telerobotic ultrasound system capable of real-time, soft-tissue imaging. Expanding on this capability, the aim of this work was to develop and characterize an image-based technique for real-time detection of prostate displacements. Methods and Materials: Image processing techniques were implemented on spatially localized ultrasound images to generate two parameters representing prostate displacements in real time. In a phantom and five volunteers, soft-tissue targets were continuously imaged with a customized robotic manipulator while recording the two tissue displacement parameters (TDPs). Variations of the TDPs in the absence of tissue displacements were evaluated, as was the sensitivity of the TDPs to prostate translations and rotations. Robustness of the approach to probe force was also investigated. Results: With 95% confidence, the proposed method detected in vivo prostate displacements before they exceeded 2.3, 2.5, and 2.8 mm in anteroposterior, superoinferior, and mediolateral directions. Prostate pitch was detected before exceeding 4.7° at 95% confidence. Total system time lag averaged 173 ms, mostly limited by ultrasound acquisition rate. False positives (FPs) (FP) in the absence of displacements did not exceed 1.5 FP events per 10 min of continuous in vivo imaging time. Conclusions: The feasibility of using telerobotic ultrasound for real-time, soft-tissue–based monitoring of target displacements was confirmed in vivo. Such monitoring has the potential to detect small clinically relevant intrafractional variations of the prostate position during beam delivery.

  20. A comparative study of recombinant and native frutalin binding to human prostate tissues

    Directory of Open Access Journals (Sweden)

    Domingues Lucília

    2009-09-01

    Full Text Available Abstract Background Numerous studies indicate that cancer cells present an aberrant glycosylation pattern that can be detected by lectin histochemistry. Lectins have shown the ability to recognise these modifications in several carcinomas, namely in the prostate carcinoma, one of the most lethal diseases in man. Thus, the aim of this work was to investigate if the α-D-galactose-binding plant lectin frutalin is able to detect such changes in the referred carcinoma. Frutalin was obtained from different sources namely, its natural source (plant origin and a recombinant source (Pichia expression system. Finally, the results obtained with the two lectins were compared and their potential use as prostate tumour biomarkers was discussed. Results The binding of recombinant and native frutalin to specific glycoconjugates expressed in human prostate tissues was assessed by using an immuhistochemical technique. A total of 20 cases of prostate carcinoma and 25 cases of benign prostate hyperplasia were studied. Lectins bound directly to the tissues and anti-frutalin polyclonal antibody was used as the bridge to react with the complex biotinilated anti-rabbit IgG plus streptavidin-conjugated peroxidase. DAB was used as visual indicator to specifically localise the binding of the lectins to the tissues. Both lectins bound to the cells cytoplasm of the prostate carcinoma glands. The binding intensity of native frutalin was stronger in the neoplasic cells than in hyperplasic cells; however no significant statistical correlation could be found (P = 0.051. On the other hand, recombinant frutalin bound exclusively to the neoplasic cells and a significant positive statistical correlation was obtained (P Conclusion Native and recombinant frutalin yielded different binding responses in the prostate tissues due to their differences in carbohydrate-binding affinities. Also, this study shows that both lectins may be used as histochemical biomarkers for the prostate

  1. Expression and role of the angiotensin II AT2 receptor in human prostate tissue: in search of a new therapeutic option for prostate cancer.

    Science.gov (United States)

    Guimond, Marie-Odile; Battista, Marie-Claude; Nikjouitavabi, Fatemeh; Carmel, Maude; Barres, Véronique; Doueik, Alexandre A; Fazli, Ladan; Gleave, Martin; Sabbagh, Robert; Gallo-Payet, Nicole

    2013-07-01

    Evidence shows that angiotensin II type 1 receptor (AT1R) blockers may be associated with improved outcome in prostate cancer patients. It has been proposed that part of this effect could be due to angiotensin II type 2 receptor (AT2R) activation, the only active angiotensin II receptor in this situation. This study aimed to characterize the localization and expression of AT2R in prostate tissues and to assess its role on cell morphology and number in prostatic epithelial cells in primary culture. AT2R and its AT2R-interacting protein (ATIP) expression were assessed on non-tumoral and tumoral human prostate using tissue microarray immunohistochemistry, binding assay, and Western blotting. AT2R effect on cell number was measured in primary cultures of epithelial cells from non-tumoral human prostate. AT2R was localized at the level of the acinar epithelial layer and its expression decreased in cancers with a Gleason score 6 or higher. In contrast, ATIP expression increased with cancer progression. Treatment of primary cell cultures from non-tumoral prostate tissues with C21/M024, a selective AT2R agonist, alone or in co-incubation with losartan, an AT1R antagonist, significantly decreased cell number compared to untreated cells. AT2R and ATIP are present in non-tumoral human prostate tissues and differentially regulated according to Gleason score. The decrease in non-tumoral prostate cell number upon selective AT2R stimulation suggests that AT2R may have a protective role against prostate cancer development. Treatment with a selective AT2R agonist could represent a new approach for prostate cancer prevention or for patients on active surveillance. Copyright © 2013 Wiley Periodicals, Inc.

  2. The effect of radiation on bcl-2 and bax in hyperplastic prostatic tissues

    International Nuclear Information System (INIS)

    Ma Qingjie; Li Yuxin; Gu Xinquan; Cao Xia; Zhao Jie; Kong Xiangbo; Cai Shanyu

    2004-01-01

    Aim: To investigate the expressions of bcl-2 and bax in benign prostatic hyperplasia (BPH) and the effect of β-rays on bcl-2 and bax. Methods: The expressions of bcl-2 and bax are studied by means of immunohistochemical method in 9 normal prostate (NP) and 15 BPH and 35 patients treated with 90Sr/90Y Prostatic Hyperplasia Applicator. Results: The expressions of bcl-2 in epithelia of NP and BPH are higher than that in stroma P<0.01=. The expressions of bcl-2 in epithelia and stroma of BPH are higher than that in NP P<0.01=. The expressions of bax in epithelia of NP are higher than that in BPH P<0.05=. However ,the expressions of bcl-2 in epithelia and stroma of BPH are higher than bax P<0.01 =. Compared with the control group, the expressions of bcl-2 in epithelia and stroma of BPH treated with 90Sr/90Y Prostatic Hyperplasia Applicator decreased and the expressions of bax increased P<0.01=. Conclusion: bcl-2 gene and bax gene play an important role in the regulation of prostatic apoptosis and the treatment of β-rays can accelerate the apoptosis of prostatic tissues. (authors)

  3. Tookad-mediated photodynamic effects on the prostate and its adjacent tissues: in vivo study in canine models

    Science.gov (United States)

    Huang, Zheng; Chen, Qun; Luck, David; Beckers, Jill; Blanc, Dominique; Hetzel, Fred W.

    2005-04-01

    Photodynamic therapy (PDT) mediated with a vascular acting photosensitizer Tookad (pd-bacteriopheophorbide), was investigated as an alternative treatment modality for prostate cancer. Tookad photodynamic effects on the prostate and its adjacent tissues were evaluated in canine models. Interstitial prostate PDT was performed by irradiating individual lobes with a diode laser (763 nm) and 1-cm cylindrical diffuser fibers at various light doses to activate the IV administered photosensitizer Tookad (1 - 2 mg/kg). The sensitivity of the adjacent tissues to Tookad-PDT was determined by superficially irradiating the surfaces of the bladder, colon, abdominal muscle and pelvic plexus with a microlens fiber at various drug/light doses. PDT effect on the prostatic urethra was evaluated by transurethral irradiation. The prostate and adjacent tissues were harvested one-week after the treatment and subjected to histopathologic examination. At one-week post interstitial prostate PDT, the animals recovered well with little or no urethral complications. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. The bladder, colon, abdominal muscle and pelvic plexus, appeared to also be sensitive to Tookad-PDT at light dose levels greater than 40 Jcm2. Urethral mucosa appeared less sensitive to Tookad-PDT. In conclusion, Tookad-mediated PDT demonstrates very strong vascular effects and can provide an effective alternative for the treatment of localized prostate cancer. Protection of the adjacent tissues should be taken into consideration in the total prostate ablation process due to their sensitivity to the Tookad-mediated PDT.

  4. Clinical utility of the percentage of positive prostate biopsies in predicting prostate cancer-specific and overall survival after radiotherapy for patients with localized prostate cancer

    International Nuclear Information System (INIS)

    D'Amico, Anthony V.; Keshaviah, Aparna; Manola, Judith; Cote, Kerri; Loffredo, Marian; Iskrzytzky, Olga; Renshaw, Andrew A.

    2002-01-01

    Purpose: To determine whether the percentage of positive prostate biopsies provides clinically relevant information to a previously established risk stratification system with respect to the end points of prostate cancer-specific survival (PCSS) and overall survival after radiotherapy for patients with clinically localized prostate cancer. Methods and Materials: A Cox regression multivariable analysis was used to evaluate the ability of the percentage of positive prostate biopsies to predict PCSS and overall survival for 381 men who underwent radiotherapy for localized prostate cancer during the prostate-specific antigen era. Results: At a median follow-up of 4.3 years (range 0.8-13.3), the presence of ≤50% positive biopsies vs. >50% positive biopsies provided a clinically relevant stratification of the 7-year estimates of PCSS (100% vs. 57%, p=0.004) in intermediate-risk patients. Moreover, all patients could be stratified into a minimal or high-risk cohort on the basis of the 10-year estimates of PCSS (100% vs. 55%, p 50%] intermediate-risk + high-risk) cohort for prostate cancer-specific death after conventional dose radiotherapy. Additional follow-up and independent validation are needed to confirm these findings

  5. Epigenetics-related genes in prostate cancer: expression profile in prostate cancer tissues, androgen-sensitive and -insensitive cell lines.

    Science.gov (United States)

    Shaikhibrahim, Zaki; Lindstrot, Andreas; Ochsenfahrt, Jacqueline; Fuchs, Kerstin; Wernert, Nicolas

    2013-01-01

    Epigenetic changes have been suggested to drive prostate cancer (PCa) development and progression. Therefore, in this study, we aimed to identify novel epigenetics-related genes in PCa tissues, and to examine their expression in metastatic PCa cell lines. We analyzed the expression of epigenetics-related genes via a clustering analysis based on gene function in moderately and poorly differentiated PCa glands compared to normal glands of the peripheral zone (prostate proper) from PCa patients using Whole Human Genome Oligo Microarrays. Our analysis identified 12 epigenetics-related genes with a more than 2-fold increase or decrease in expression and a p-value epigenetics-related genes that we identified in primary PCa tissues may provide further insight into the role that epigenetic changes play in PCa. Moreover, some of the genes that we identified may play important roles in primary PCa and metastasis, in primary PCa only, or in metastasis only. Follow-up studies are required to investigate the functional role and the role that the expression of these genes play in the outcome and progression of PCa using tissue microarrays.

  6. Tissue mimicking materials for a multi-imaging modality prostate phantom

    International Nuclear Information System (INIS)

    D'Souza, Warren D.; Madsen, Ernest L.; Unal, Orhan; Vigen, Karl K.; Frank, Gary R.; Thomadsen, Bruce R.

    2001-01-01

    Materials that simultaneously mimic soft tissue in vivo for magnetic resonance imaging (MRI), ultrasound (US), and computed tomography (CT) for use in a prostate phantom have been developed. Prostate and muscle mimicking materials contain water, agarose, lipid particles, protein, Cu ++ , EDTA, glass beads, and thimerosal (preservative). Fat was mimicked with safflower oil suffusing a random mesh (network) of polyurethane. Phantom material properties were measured at 22 deg. C. (22 deg. C is a typical room temperature at which phantoms are used.) The values of material properties should match, as well as possible, the values for tissues at body temperature, 37 deg. C. For MRI, the primary properties of interest are T1 and T2 relaxations times, for US they are the attenuation coefficient, propagation speed, and backscatter, and for CT, the x-ray attenuation. Considering the large number of parameters to be mimicked, rather good agreement was found with actual tissue values obtained from the literature. Using published values for prostate parenchyma, T1 and T2 at 37 deg. C and 40 MHz are estimated to be about 1100 and 98 ms, respectively. The CT number for in vivo prostate is estimated to be 45 HU (Hounsfield units). The prostate mimicking material has a T1 of 937 ms and a T2 of 88 ms at 22 deg. C and 40 MHz; the propagation speed and attenuation coefficient slope are 1540 m/s and 0.36 dB/cm/MHz, respectively, and the CT number of tissue mimicking prostate is 43 HU. Tissue mimicking (TM) muscle differs from TM prostate in the amount of dry weight agarose, Cu ++ , EDTA, and the quality and quantity of glass beads. The 18 μm glass beads used in TM muscle increase US backscatter and US attenuation; the presence of the beads also has some effect on T1 but no effect on T2. The composition of tissue-mimicking materials developed is such that different versions can be placed in direct contact with one another in a phantom with no long term change in US, MRI, or CT

  7. Immunohistochemical Detection and Localization of Somatostatin Receptor Subtypes in Prostate Tissue from Patients with Bladder Outlet Obstruction

    Directory of Open Access Journals (Sweden)

    Rodolfo Montironi

    2008-01-01

    Full Text Available Background and Aim of the Study: Scant information on the cellular distribution of the five somatostatin receptor (SSTR subtypes in the normal prostate and in neoplasms of the prostate has been reported in very few studies in which techniques, such as in situ hybridization histochemistry, autoradiography, and more recently immunohistochemistry, have been applied. The aim of the study was to examine immunohistochemically the distribution and localization of these 5 subtypes in the various tissue components in normal prostate.

  8. Predictive factors of unfavorable prostate cancer in patients who underwent prostatectomy but eligible for active surveillance

    Directory of Open Access Journals (Sweden)

    Seol Ho Choo

    2014-06-01

    Conclusions: A significant proportion of patients who were candidates for active surveillance had unfavorable prostate cancer. Age, PSA density, and two positive cores were independent significant predictive factors for unfavorable prostate cancer. These factors should be considered when performing active surveillance.

  9. Selective expression of myosin IC Isoform A in mouse and human cell lines and mouse prostate cancer tissues.

    Directory of Open Access Journals (Sweden)

    Ivanna Ihnatovych

    Full Text Available Myosin IC is a single headed member of the myosin superfamily. We recently identified a novel isoform and showed that the MYOIC gene in mammalian cells encodes three isoforms (isoforms A, B, and C. Furthermore, we demonstrated that myosin IC isoform A but not isoform B exhibits a tissue specific expression pattern. In this study, we extended our analysis of myosin IC isoform expression patterns by analyzing the protein and mRNA expression in various mammalian cell lines and in various prostate specimens and tumor tissues from the transgenic mouse prostate (TRAMP model by immunoblotting, qRT-PCR, and by indirect immunohistochemical staining of paraffin embedded prostate specimen. Analysis of a panel of mammalian cell lines showed an increased mRNA and protein expression of specifically myosin IC isoform A in a panel of human and mouse prostate cancer cell lines but not in non-cancer prostate or other (non-prostate- cancer cell lines. Furthermore, we demonstrate that myosin IC isoform A expression is significantly increased in TRAMP mouse prostate samples with prostatic intraepithelial neoplasia (PIN lesions and in distant site metastases in lung and liver when compared to matched normal tissues. Our observations demonstrate specific changes in the expression of myosin IC isoform A that are concurrent with the occurrence of prostate cancer in the TRAMP mouse prostate cancer model that closely mimics clinical prostate cancer. These data suggest that elevated levels of myosin IC isoform A may be a potential marker for the detection of prostate cancer.

  10. Updating risk prediction tools: a case study in prostate cancer.

    Science.gov (United States)

    Ankerst, Donna P; Koniarski, Tim; Liang, Yuanyuan; Leach, Robin J; Feng, Ziding; Sanda, Martin G; Partin, Alan W; Chan, Daniel W; Kagan, Jacob; Sokoll, Lori; Wei, John T; Thompson, Ian M

    2012-01-01

    Online risk prediction tools for common cancers are now easily accessible and widely used by patients and doctors for informed decision-making concerning screening and diagnosis. A practical problem is as cancer research moves forward and new biomarkers and risk factors are discovered, there is a need to update the risk algorithms to include them. Typically, the new markers and risk factors cannot be retrospectively measured on the same study participants used to develop the original prediction tool, necessitating the merging of a separate study of different participants, which may be much smaller in sample size and of a different design. Validation of the updated tool on a third independent data set is warranted before the updated tool can go online. This article reports on the application of Bayes rule for updating risk prediction tools to include a set of biomarkers measured in an external study to the original study used to develop the risk prediction tool. The procedure is illustrated in the context of updating the online Prostate Cancer Prevention Trial Risk Calculator to incorporate the new markers %freePSA and [-2]proPSA measured on an external case-control study performed in Texas, U.S.. Recent state-of-the art methods in validation of risk prediction tools and evaluation of the improvement of updated to original tools are implemented using an external validation set provided by the U.S. Early Detection Research Network. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Is it possible to predict low-volume and insignificant prostate cancer by core needle biopsies?

    DEFF Research Database (Denmark)

    Berg, Kasper Drimer; Toft, Birgitte Grønkaer; Røder, Martin Andreas

    2013-01-01

    M: tumour ≤5% of total prostate volume and prostate-specific antigen (PSA) ≤10 ng/mL. In all definitions, Gleason score (GS) was ≤6 and the tumour was organ confined. Biopsies alone performed poorly as a predictor of unifocal and unilateral cancer in the prostatectomy specimens with positive predictive......In an attempt to minimize overtreatment of localized prostate cancer (PCa) active surveillance (AS) and minor invasive procedures have received increased attention. We investigated the accuracy of pre-operative findings in defining insignificant disease and distinguishing between unilateral.......9% and 12.0%, respectively, for identifying InsigM, InsigW and InsigE in the prostate specimen. Conclusively, routine prostate biopsies cannot predict unifocal and unilateral PCa, and must be regarded insufficient to select patients for focal therapy. Although candidates for AS may be identified using...

  12. [Distribution and significance of α1-adrenoceptor subtypes in patients with chronic prostatitis in prostate, bladder detrusor and posterior urethral tissue].

    Science.gov (United States)

    Yang, Yu; Xie, Hui; Zheng, Jian-jian; Chen, Bi-cheng; He, Qiu-xiang; Shen, Ji-hong

    2010-12-14

    To study the distribution of alpha1-adrenoceptor (α1-AR) subtype in prostate, posterior urethra and bladder detrusor of patients with chronic prostatitis (CP). The prostate specimens were collected at autopsy from 30 organ donors (aged 20-35 years old) dying of non-prostatic diseases. The pathological specimens of prostate peripheral zone were examined. The method of real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) was employed for quantification of α1a-AR and α1b-AR subtype expression in prostate transition zone and its surrounding zone, posterior urethra and bladder detrusor tissue. Among all donors, there were 24 cases with pathological inflammation in prostatic peripheral zone and 6 with pathological non-inflammation. The mRNA expression of α1-AR subtypes in bladder detrusor and posterior urethra was significantly higher in the inflammation group than in the control group (Pposterior urethra was significantly lower in the inflammation group than in the control group (Pposterior urethra may explain various urodynamic changes in CP and lead to the occurrence and development of CP in prostate, posterior urethra and bladder detrusor.

  13. Potential upstream regulators of cannabinoid receptor 1 signaling in prostate cancer: a Bayesian network analysis of data from a tissue microarray.

    Science.gov (United States)

    Häggström, Jenny; Cipriano, Mariateresa; Forshell, Linus Plym; Persson, Emma; Hammarsten, Peter; Stella, Nephi; Fowler, Christopher J

    2014-08-01

    The endocannabinoid system regulates cancer cell proliferation, and in prostate cancer a high cannabinoid CB1 receptor expression is associated with a poor prognosis. Down-stream mediators of CB1 receptor signaling in prostate cancer are known, but information on potential upstream regulators is lacking. Data from a well-characterized tumor tissue microarray were used for a Bayesian network analysis using the max-min hill-climbing method. In non-malignant tissue samples, a directionality of pEGFR (the phosphorylated form of the epidermal growth factor receptor) → CB1 receptors were found regardless as to whether the endocannabinoid metabolizing enzyme fatty acid amide hydrolase (FAAH) was included as a parameter. A similar result was found in the tumor tissue, but only when FAAH was included in the analysis. A second regulatory pathway, from the growth factor receptor ErbB2 → FAAH was also identified in the tumor samples. Transfection of AT1 prostate cancer cells with CB1 receptors induced a sensitivity to the growth-inhibiting effects of the CB receptor agonist CP55,940. The sensitivity was not dependent upon the level of receptor expression. Thus a high CB1 receptor expression alone does not drive the cells towards a survival phenotype in the presence of a CB receptor agonist. The data identify two potential regulators of the endocannabinoid system in prostate cancer and allow the construction of a model of a dysregulated endocannabinoid signaling network in this tumor. Further studies should be designed to test the veracity of the predictions of the network analysis in prostate cancer and other solid tumors. © 2014 The Authors. The Prostate published by Wiley Periodicals, Inc.

  14. Quantitative assessment of the mechanical properties of prostate tissue with optical coherence elastography

    Science.gov (United States)

    Ling, Yuting; Li, Chunhui; Zhou, Kanheng; Guan, Guangying; Lang, Stephen; McGloin, David; Nabi, Ghulam; Huang, Zhihong

    2018-02-01

    Prostate cancer (PCa) is a heterogeneous disease with multifocal origin. In current clinical care, the Gleason scoring system is the well-established diagnosis by microscopic evaluation of the tissue from trans-rectal ultrasound (TRUS) guided biopsies. Nevertheless, the sensitivity and specificity in detecting PCa can range from 40 to 50% for conventional TRUS B-mode imaging. Tissue elasticity is associated with the disease progression and elastography technique has recently shown promise in aiding PCa diagnosis. However, many cancer foci in the prostate gland has very small size less than 1 mm and those detected by medical elastography were larger than 2 mm. Hereby, we introduce optical coherence elastography (OCE) to quantify the prostate stiffness with high resolution in the magnitude of 10 µm. Following our feasibility study of 10 patients reported previously, we recruited 60 more patients undergoing 12-core TRUS guided biopsies for suspected PCa with a total of 720 biopsies. The stiffness of cancer tissue was approximately 57.63% higher than that of benign ones. Using histology as reference standard and cut-off threshold of 600kPa, the data analysis showed sensitivity and specificity of 89.6% and 99.8% respectively. The method also demonstrated potential in characterising different grades of PCa based on the change of tissue morphology and quantitative mechanical properties. In conclusion, quantitative OCE can be a reliable technique to identify PCa lesion and differentiate indolent from aggressive cancer.

  15. Nomogram to predict rectal toxicity following prostate cancer radiotherapy.

    Directory of Open Access Journals (Sweden)

    Jean-Bernard Delobel

    Full Text Available To identify predictors of acute and late rectal toxicity following prostate cancer radiotherapy (RT, while integrating the potential impact of RT technique, dose escalation, and moderate hypofractionation, thus enabling us to generate a nomogram for individual prediction.In total, 972 patients underwent RT for localized prostate cancer, to a total dose of 70 Gy or 80 Gy, using two different fractionations (2 Gy or 2.5 Gy/day, by means of several RT techniques (3D conformal RT [3DCRT], intensity-modulated RT [IMRT], or image-guided RT [IGRT]. Multivariate analyses were performed to identify predictors of acute and late rectal toxicity. A nomogram was generated based on the logistic regression model used to predict the 3-year rectal toxicity risk, with its accuracy assessed by dividing the cohort into training and validation subgroups.Mean follow-up for the entire cohort was 62 months, ranging from 6 to 235. The rate of acute Grade ≥2 rectal toxicity was 22.2%, decreasing when combining IMRT and IGRT, compared to 3DCRT (RR = 0.4, 95%CI: 0.3-0.6, p<0.01. The 5-year Grade ≥2 risks for rectal bleeding, urgency/tenesmus, diarrhea, and fecal incontinence were 9.9%, 4.5%, 2.8%, and 0.4%, respectively. The 3-year Grade ≥2 risk for overall rectal toxicity increased with total dose (p<0.01, RR = 1.1, 95%CI: 1.0-1.1 and dose per fraction (2Gy vs. 2.5Gy (p = 0.03, RR = 3.3, 95%CI: 1.1-10.0, and decreased when combining IMRT and IGRT (RR = 0.50, 95% CI: 0.3-0.8, p<0.01. Based on these three parameters, a nomogram was generated.Dose escalation and moderate hypofractionation increase late rectal toxicity. IMRT combined with IGRT markedly decreases acute and late rectal toxicity. Performing combined IMRT and IGRT can thus be envisaged for dose escalation and moderate hypofractionation. Our nomogram predicts the 3-year rectal toxicity risk by integrating total dose, fraction dose, and RT technique.

  16. Random Forests to Predict Rectal Toxicity Following Prostate Cancer Radiation Therapy

    International Nuclear Information System (INIS)

    Ospina, Juan D.; Zhu, Jian; Chira, Ciprian; Bossi, Alberto; Delobel, Jean B.; Beckendorf, Véronique; Dubray, Bernard; Lagrange, Jean-Léon; Correa, Juan C.

    2014-01-01

    Purpose: To propose a random forest normal tissue complication probability (RF-NTCP) model to predict late rectal toxicity following prostate cancer radiation therapy, and to compare its performance to that of classic NTCP models. Methods and Materials: Clinical data and dose-volume histograms (DVH) were collected from 261 patients who received 3-dimensional conformal radiation therapy for prostate cancer with at least 5 years of follow-up. The series was split 1000 times into training and validation cohorts. A RF was trained to predict the risk of 5-year overall rectal toxicity and bleeding. Parameters of the Lyman-Kutcher-Burman (LKB) model were identified and a logistic regression model was fit. The performance of all the models was assessed by computing the area under the receiving operating characteristic curve (AUC). Results: The 5-year grade ≥2 overall rectal toxicity and grade ≥1 and grade ≥2 rectal bleeding rates were 16%, 25%, and 10%, respectively. Predictive capabilities were obtained using the RF-NTCP model for all 3 toxicity endpoints, including both the training and validation cohorts. The age and use of anticoagulants were found to be predictors of rectal bleeding. The AUC for RF-NTCP ranged from 0.66 to 0.76, depending on the toxicity endpoint. The AUC values for the LKB-NTCP were statistically significantly inferior, ranging from 0.62 to 0.69. Conclusions: The RF-NTCP model may be a useful new tool in predicting late rectal toxicity, including variables other than DVH, and thus appears as a strong competitor to classic NTCP models

  17. The classification of benign and malignant human prostate tissue by multivariate analysis of {sup 1}H magnetic resonance spectra

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, P.; Smith, I.; Leboldus, L.; Littman, C.; Somorjai, L.; Bezabeh, T. [Institute for Biodiagnostic, National Research Council, Manitoba (Canada)

    1998-04-01

    {sup 1}H magnetic resonance spectroscopy studies (360 MHz) were performed on specimens of benign (n = 66) and malignant (n = 21) human prostate tissue from 50 patients and the spectral data were subjected to multivariate analysis, specifically linear-discriminant analysis. On the basis of histopathological assessments, an overall classification accuracy of 96.6 % was achieved, with a sensitivity of 100 % and a specificity of 95.5 % in classifying benign prostatic hyperplasia from prostatic cancer. Resonances due to citrate, glutamate, and taurine were among the six spectral subregions identified by our algorithm as having diagnostic potential. Significantly higher levels of citrate were observed in glandular than in stromal benign prostatic hyperplasia (P < 0.05). This method shows excellent promise for the possibility of in vivo assessment of prostate tissue by magnetic resonance. (author)

  18. 3D prostate histology image reconstruction: Quantifying the impact of tissue deformation and histology section location

    Directory of Open Access Journals (Sweden)

    Eli Gibson

    2013-01-01

    Full Text Available Background: Guidelines for localizing prostate cancer on imaging are ideally informed by registered post-prostatectomy histology. 3D histology reconstruction methods can support this by reintroducing 3D spatial information lost during histology processing. The need to register small, high-grade foci drives a need for high accuracy. Accurate 3D reconstruction method design is impacted by the answers to the following central questions of this work. (1 How does prostate tissue deform during histology processing? (2 What spatial misalignment of the tissue sections is induced by microtome cutting? (3 How does the choice of reconstruction model affect histology reconstruction accuracy? Materials and Methods: Histology, paraffin block face and magnetic resonance images were acquired for 18 whole mid-gland tissue slices from six prostates. 7-15 homologous landmarks were identified on each image. Tissue deformation due to histology processing was characterized using the target registration error (TRE after landmark-based registration under four deformation models (rigid, similarity, affine and thin-plate-spline [TPS]. The misalignment of histology sections from the front faces of tissue slices was quantified using manually identified landmarks. The impact of reconstruction models on the TRE after landmark-based reconstruction was measured under eight reconstruction models comprising one of four deformation models with and without constraining histology images to the tissue slice front faces. Results: Isotropic scaling improved the mean TRE by 0.8-1.0 mm (all results reported as 95% confidence intervals, while skew or TPS deformation improved the mean TRE by <0.1 mm. The mean misalignment was 1.1-1.9΀ (angle and 0.9-1.3 mm (depth. Using isotropic scaling, the front face constraint raised the mean TRE by 0.6-0.8 mm. Conclusions: For sub-millimeter accuracy, 3D reconstruction models should not constrain histology images to the tissue slice front faces and

  19. Analysis of Mel-18 expression in prostate cancer tissues and correlation with clinicopathologic features.

    Science.gov (United States)

    Wang, Wei; Lin, Tianxin; Huang, Jian; Hu, Weilie; Xu, Kewei; Liu, Jun

    2011-01-01

    Mel-18 is a member of the polycomb group (PcG) of proteins, which are chromatin regulatory factors that play an important role in development and oncogenesis. This study was designed to investigate the clinical and prognostic significance of Mel-18 in the patients with prostate cancer. Immunostaining with Mel-18 specific antibodies was performed on paraffin sections from 202 patients. Correlations between Mel-18 and the Gleason grading system, clinical stage, serum prostate-specific antigen (PSA) levels, and age were evaluated. PSA recurrence in 76 patients who underwent radical prostatectomy and survival in 59 patients with metastases at diagnosis were analyzed to evaluate the influence of Mel-18 expression in cancer progression using Kaplan-Meier analysis and multivariate Cox regression analysis. Staining was seen in all prostatic tissues. Mel-18 expression was significantly reduced in the prostate cancer patients with PSA levels over 100 ng/ml (P=0.009), advanced clinical stage (>T4, N1, or M1 disease, P=0.029), higher Gleason grade or with a higher Gleason score (P=0.018) than in those with other clinicopathologic features. Negative expression of Mel-18 was associated with significantly higher rates of PSA recurrence after radical prostatectomy than with positive expression of Mel-18 (P = 0.029), and was an independent predictor of PSA recurrence (P=0.034, HR=2.143) in multivariate analysis. Similarly, metastatic prostate cancer patients with negative expression of Mel-18 showed significantly worse survival compared with the positive expression of Mel-18 (P=0.025). In multivariate analysis, negative expression of Mel-18 was an independent predictor of cancer-specific survival (P=0.024, HR=2.365). Our study provides important evidence for the recognition of Mel-18 as a tumor suppressor. The expression of Mel-18 showed potential as a prognostic marker for human prostate cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Microlocalization and Quantitation of Risk Associated Elements in Gleason Graded Prostate Tissue

    Science.gov (United States)

    2007-03-01

    ORGANIZATION: Regents of the University of California Maya Conn Los Angeles CA 90024 REPORT DATE: March 2007 TYPE OF REPORT...California Maya Conn Los Angeles CA 90024 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM(S...carcinoma of different histological grading in comparison to normal prostate tissue and adenofibromyomatosis (BPH) Uro Res 10:301-303. 5. Feustel A

  1. Use of artificial neural networks to predict biological outcomes for patients receiving radical radiotherapy of the prostate

    International Nuclear Information System (INIS)

    Gulliford, Sarah L.; Webb, Steve; Rowbottom, Carl G.; Corne, David W.; Dearnaley, David P.

    2004-01-01

    Background and purpose: This paper discusses the application of artificial neural networks (ANN) in predicting biological outcomes following prostate radiotherapy. A number of model-based methods have been developed to correlate the dose distributions calculated for a patient receiving radiotherapy and the radiobiological effect this will produce. Most widely used are the normal tissue complication probability and tumour control probability models. An alternative method for predicting specific examples of tumour control and normal tissue complications is to use an ANN. One of the advantages of this method is that there is no need for a priori information regarding the relationship between the data being correlated. Patients and methods: A set of retrospective clinical data from patients who received radical prostate radiotherapy was used to train ANNs to predict specific biological outcomes by learning the relationship between the treatment plan prescription, dose distribution and the corresponding biological effect. The dose and volume were included as a differential dose-volume histogram in order to provide a holistic description of the available data. Results: It was shown that the ANNs were able to predict biochemical control and specific bladder and rectum complications with sensitivity and specificity of above 55% when the outcomes were dichotomised. It was also possible to analyse information from the ANNs to investigate the effect of individual treatment parameters on the outcome. Conclusion: ANNs have been shown to learn something of the complex relationship between treatment parameters and outcome which, if developed further, may prove to be a useful tool in predicting biological outcomes

  2. A tissue biopsy-based epigenetic multiplex PCR assay for prostate cancer detection

    Directory of Open Access Journals (Sweden)

    Van Neste Leander

    2012-06-01

    Full Text Available Abstract Background PSA-directed prostate cancer screening leads to a high rate of false positive identifications and an unnecessary biopsy burden. Epigenetic biomarkers have proven useful, exhibiting frequent and abundant inactivation of tumor suppressor genes through such mechanisms. An epigenetic, multiplex PCR test for prostate cancer diagnosis could provide physicians with better tools to help their patients. Biomarkers like GSTP1, APC and RASSF1 have demonstrated involvement with prostate cancer, with the latter two genes playing prominent roles in the field effect. The epigenetic states of these genes can be used to assess the likelihood of cancer presence or absence. Results An initial test cohort of 30 prostate cancer-positive samples and 12 cancer-negative samples was used as basis for the development and optimization of an epigenetic multiplex assay based on the GSTP1, APC and RASSF1 genes, using methylation specific PCR (MSP. The effect of prostate needle core biopsy sample volume and age of formalin-fixed paraffin-embedded (FFPE samples was evaluated on an independent follow-up cohort of 51 cancer-positive patients. Multiplexing affects copy number calculations in a consistent way per assay. Methylation ratios are therefore altered compared to the respective singleplex assays, but the correlation with patient outcome remains equivalent. In addition, tissue-biopsy samples as small as 20 μm can be used to detect methylation in a reliable manner. The age of FFPE-samples does have a negative impact on DNA quality and quantity. Conclusions The developed multiplex assay appears functionally similar to individual singleplex assays, with the benefit of lower tissue requirements, lower cost and decreased signal variation. This assay can be applied to small biopsy specimens, down to 20 microns, widening clinical applicability. Increasing the sample volume can compensate the loss of DNA quality and quantity in older samples.

  3. 3D conformal MRI-controlled transurethral ultrasound prostate therapy: validation of numerical simulations and demonstration in tissue-mimicking gel phantoms.

    Science.gov (United States)

    Burtnyk, Mathieu; N'Djin, William Apoutou; Kobelevskiy, Ilya; Bronskill, Michael; Chopra, Rajiv

    2010-11-21

    MRI-controlled transurethral ultrasound therapy uses a linear array of transducer elements and active temperature feedback to create volumes of thermal coagulation shaped to predefined prostate geometries in 3D. The specific aims of this work were to demonstrate the accuracy and repeatability of producing large volumes of thermal coagulation (>10 cc) that conform to 3D human prostate shapes in a tissue-mimicking gel phantom, and to evaluate quantitatively the accuracy with which numerical simulations predict these 3D heating volumes under carefully controlled conditions. Eleven conformal 3D experiments were performed in a tissue-mimicking phantom within a 1.5T MR imager to obtain non-invasive temperature measurements during heating. Temperature feedback was used to control the rotation rate and ultrasound power of transurethral devices with up to five 3.5 × 5 mm active transducer elements. Heating patterns shaped to human prostate geometries were generated using devices operating at 4.7 or 8.0 MHz with surface acoustic intensities of up to 10 W cm(-2). Simulations were informed by transducer surface velocity measurements acquired with a scanning laser vibrometer enabling improved calculations of the acoustic pressure distribution in a gel phantom. Temperature dynamics were determined according to a FDTD solution to Pennes' BHTE. The 3D heating patterns produced in vitro were shaped very accurately to the prostate target volumes, within the spatial resolution of the MRI thermometry images. The volume of the treatment difference falling outside ± 1 mm of the target boundary was, on average, 0.21 cc or 1.5% of the prostate volume. The numerical simulations predicted the extent and shape of the coagulation boundary produced in gel to within (mean ± stdev [min, max]): 0.5 ± 0.4 [-1.0, 2.1] and -0.05 ± 0.4 [-1.2, 1.4] mm for the treatments at 4.7 and 8.0 MHz, respectively. The temperatures across all MRI thermometry images were predicted within -0.3 ± 1.6 °C and 0

  4. Widespread high grade prostatic intraepithelial neoplasia on biopsy predicts the risk of prostate cancer: A 12 months analysis after three consecutive prostate biopsies

    Directory of Open Access Journals (Sweden)

    Cosimo De Nunzio

    2013-06-01

    Full Text Available Purpose: To evaluate the risk of prostate cancer (PCa on a third prostate biopsy in a group of patients with two consecutive diagnoses of high grade intraepithelial neoplasia (HGPIN. Materials and methods: From November 2004 to December 2007, patients referred to our clinic with a PSA ! 4 ng/ml or an abnormal digital rectal examination (DRE were scheduled for trans-rectal ultrasound (TRUS guided 12-core prostate biopsy. Patients with HGPIN underwent a second prostate biopsy, and if the results of such procedure yielded a second diagnosis of HGPIN, we proposed a third 12-core needle biopsy regardless of PSA value. Crude and adjusted logistic regressions were used to assess predictors of PCa on the third biopsy. Results: A total of 650 patients underwent 12 cores transrectal ultrasound prostatic biopsy in the study period. Of 147 (22% men with a diagnosis of HGPIN, 117 underwent a second prostatic biopsy after six months and 43 a third biopsy after other six months. After the third biopsy, 19 patients (34% still showed HGPIN, 15 (35% were diagnosed with PCa and 9 (21% presented with chronic prostatitis. Widespread HGPIN on a second biopsy was significantly associated with PCa on further biopsy (!2 = 4.04, p = 0.04. Moreover, the presence of widespread HGPIN significantly predicted the risk of PCa on crude and adjusted logistic regressions. Conclusions: Widespread HGPIN on second biopsy is associated with the presence of PCa on a third biopsy. Nonetheless, the relationship between HGPIN and PCa remains complex and further studies are needed to confirm our findings.

  5. Models for predicting objective function weights in prostate cancer IMRT

    International Nuclear Information System (INIS)

    Boutilier, Justin J.; Lee, Taewoo; Craig, Tim; Sharpe, Michael B.; Chan, Timothy C. Y.

    2015-01-01

    Purpose: To develop and evaluate the clinical applicability of advanced machine learning models that simultaneously predict multiple optimization objective function weights from patient geometry for intensity-modulated radiation therapy of prostate cancer. Methods: A previously developed inverse optimization method was applied retrospectively to determine optimal objective function weights for 315 treated patients. The authors used an overlap volume ratio (OV) of bladder and rectum for different PTV expansions and overlap volume histogram slopes (OVSR and OVSB for the rectum and bladder, respectively) as explanatory variables that quantify patient geometry. Using the optimal weights as ground truth, the authors trained and applied three prediction models: logistic regression (LR), multinomial logistic regression (MLR), and weighted K-nearest neighbor (KNN). The population average of the optimal objective function weights was also calculated. Results: The OV at 0.4 cm and OVSR at 0.1 cm features were found to be the most predictive of the weights. The authors observed comparable performance (i.e., no statistically significant difference) between LR, MLR, and KNN methodologies, with LR appearing to perform the best. All three machine learning models outperformed the population average by a statistically significant amount over a range of clinical metrics including bladder/rectum V53Gy, bladder/rectum V70Gy, and dose to the bladder, rectum, CTV, and PTV. When comparing the weights directly, the LR model predicted bladder and rectum weights that had, on average, a 73% and 74% relative improvement over the population average weights, respectively. The treatment plans resulting from the LR weights had, on average, a rectum V70Gy that was 35% closer to the clinical plan and a bladder V70Gy that was 29% closer, compared to the population average weights. Similar results were observed for all other clinical metrics. Conclusions: The authors demonstrated that the KNN and MLR

  6. Models for predicting objective function weights in prostate cancer IMRT

    Energy Technology Data Exchange (ETDEWEB)

    Boutilier, Justin J., E-mail: j.boutilier@mail.utoronto.ca; Lee, Taewoo [Department of Mechanical and Industrial Engineering, University of Toronto, 5 King’s College Road, Toronto, Ontario M5S 3G8 (Canada); Craig, Tim [Radiation Medicine Program, UHN Princess Margaret Cancer Centre, 610 University of Avenue, Toronto, Ontario M5T 2M9, Canada and Department of Radiation Oncology, University of Toronto, 148 - 150 College Street, Toronto, Ontario M5S 3S2 (Canada); Sharpe, Michael B. [Radiation Medicine Program, UHN Princess Margaret Cancer Centre, 610 University of Avenue, Toronto, Ontario M5T 2M9 (Canada); Department of Radiation Oncology, University of Toronto, 148 - 150 College Street, Toronto, Ontario M5S 3S2 (Canada); Techna Institute for the Advancement of Technology for Health, 124 - 100 College Street, Toronto, Ontario M5G 1P5 (Canada); Chan, Timothy C. Y. [Department of Mechanical and Industrial Engineering, University of Toronto, 5 King’s College Road, Toronto, Ontario M5S 3G8, Canada and Techna Institute for the Advancement of Technology for Health, 124 - 100 College Street, Toronto, Ontario M5G 1P5 (Canada)

    2015-04-15

    Purpose: To develop and evaluate the clinical applicability of advanced machine learning models that simultaneously predict multiple optimization objective function weights from patient geometry for intensity-modulated radiation therapy of prostate cancer. Methods: A previously developed inverse optimization method was applied retrospectively to determine optimal objective function weights for 315 treated patients. The authors used an overlap volume ratio (OV) of bladder and rectum for different PTV expansions and overlap volume histogram slopes (OVSR and OVSB for the rectum and bladder, respectively) as explanatory variables that quantify patient geometry. Using the optimal weights as ground truth, the authors trained and applied three prediction models: logistic regression (LR), multinomial logistic regression (MLR), and weighted K-nearest neighbor (KNN). The population average of the optimal objective function weights was also calculated. Results: The OV at 0.4 cm and OVSR at 0.1 cm features were found to be the most predictive of the weights. The authors observed comparable performance (i.e., no statistically significant difference) between LR, MLR, and KNN methodologies, with LR appearing to perform the best. All three machine learning models outperformed the population average by a statistically significant amount over a range of clinical metrics including bladder/rectum V53Gy, bladder/rectum V70Gy, and dose to the bladder, rectum, CTV, and PTV. When comparing the weights directly, the LR model predicted bladder and rectum weights that had, on average, a 73% and 74% relative improvement over the population average weights, respectively. The treatment plans resulting from the LR weights had, on average, a rectum V70Gy that was 35% closer to the clinical plan and a bladder V70Gy that was 29% closer, compared to the population average weights. Similar results were observed for all other clinical metrics. Conclusions: The authors demonstrated that the KNN and MLR

  7. Ex vivo metabolic fingerprinting identifies biomarkers predictive of prostate cancer recurrence following radical prostatectomy.

    Science.gov (United States)

    Braadland, Peder R; Giskeødegård, Guro; Sandsmark, Elise; Bertilsson, Helena; Euceda, Leslie R; Hansen, Ailin F; Guldvik, Ingrid J; Selnæs, Kirsten M; Grytli, Helene H; Katz, Betina; Svindland, Aud; Bathen, Tone F; Eri, Lars M; Nygård, Ståle; Berge, Viktor; Taskén, Kristin A; Tessem, May-Britt

    2017-11-21

    Robust biomarkers that identify prostate cancer patients with high risk of recurrence will improve personalised cancer care. In this study, we investigated whether tissue metabolites detectable by high-resolution magic angle spinning magnetic resonance spectroscopy (HR-MAS MRS) were associated with recurrence following radical prostatectomy. We performed a retrospective ex vivo study using HR-MAS MRS on tissue samples from 110 radical prostatectomy specimens obtained from three different Norwegian cohorts collected between 2002 and 2010. At the time of analysis, 50 patients had experienced prostate cancer recurrence. Associations between metabolites, clinicopathological variables, and recurrence-free survival were evaluated using Cox proportional hazards regression modelling, Kaplan-Meier survival analyses and concordance index (C-index). High intratumoural spermine and citrate concentrations were associated with longer recurrence-free survival, whereas high (total-choline+creatine)/spermine (tChoCre/Spm) and higher (total-choline+creatine)/citrate (tChoCre/Cit) ratios were associated with shorter time to recurrence. Spermine concentration and tChoCre/Spm were independently associated with recurrence in multivariate Cox proportional hazards modelling after adjusting for clinically relevant risk factors (C-index: 0.769; HR: 0.72; P=0.016 and C-index: 0.765; HR: 1.43; P=0.014, respectively). Spermine concentration and tChoCre/Spm ratio in prostatectomy specimens were independent prognostic markers of recurrence. These metabolites can be noninvasively measured in vivo and may thus offer predictive value to establish preoperative risk assessment nomograms.

  8. The predictive value of 2-year posttreatment biopsy after prostate cancer radiotherapy for eventual biochemical outcome

    International Nuclear Information System (INIS)

    Vance, Waseet; Tucker, Susan L.; Crevoisier, Renaud de; Kuban, Deborah A.; Cheung, M. Rex

    2007-01-01

    Purpose: To determine the value of a 2-year post-radiotherapy (RT) prostate biopsy for predicting eventual biochemical failure in patients who were treated for localized prostate cancer. Methods and Materials: This study comprised 164 patients who underwent a planned 2-year post-RT prostate biopsy. The independent prognostic value of the biopsy results for forecasting eventual biochemical outcome and overall survival was tested with other factors (the Gleason score, 1992 American Joint Committee on Cancer tumor stage, pretreatment prostate-specific antigen level, risk group, and RT dose) in a multivariate analysis. The current nadir + 2 (CN + 2) definition of biochemical failure was used. Patients with rising prostate-specific antigen (PSA) or suspicious digital rectal examination before the biopsy were excluded. Results: The biopsy results were normal in 78 patients, scant atypical and malignant cells in 30, carcinoma with treatment effect in 43, and carcinoma without treatment effect in 13. Using the CN + 2 definition, we found a significant association between biopsy results and eventual biochemical failure. We also found that the biopsy status provides predictive information independent of the PSA status at the time of biopsy. Conclusion: A 2-year post-RT prostate biopsy may be useful for forecasting CN + 2 biochemical failure. Posttreatment prostate biopsy may be useful for identifying patients for aggressive salvage therapy

  9. Network-directed cis-mediator analysis of normal prostate tissue expression profiles reveals downstream regulatory associations of prostate cancer susceptibility loci.

    Science.gov (United States)

    Larson, Nicholas B; McDonnell, Shannon K; Fogarty, Zach; Larson, Melissa C; Cheville, John; Riska, Shaun; Baheti, Saurabh; Weber, Alexandra M; Nair, Asha A; Wang, Liang; O'Brien, Daniel; Davila, Jaime; Schaid, Daniel J; Thibodeau, Stephen N

    2017-10-17

    Large-scale genome-wide association studies have identified multiple single-nucleotide polymorphisms associated with risk of prostate cancer. Many of these genetic variants are presumed to be regulatory in nature; however, follow-up expression quantitative trait loci (eQTL) association studies have to-date been restricted largely to cis -acting associations due to study limitations. While trans -eQTL scans suffer from high testing dimensionality, recent evidence indicates most trans -eQTL associations are mediated by cis -regulated genes, such as transcription factors. Leveraging a data-driven gene co-expression network, we conducted a comprehensive cis -mediator analysis using RNA-Seq data from 471 normal prostate tissue samples to identify downstream regulatory associations of previously identified prostate cancer risk variants. We discovered multiple trans -eQTL associations that were significantly mediated by cis -regulated transcripts, four of which involved risk locus 17q12, proximal transcription factor HNF1B , and target trans -genes with known HNF response elements ( MIA2 , SRC , SEMA6A , KIF12 ). We additionally identified evidence of cis -acting down-regulation of MSMB via rs10993994 corresponding to reduced co-expression of NDRG1 . The majority of these cis -mediator relationships demonstrated trans -eQTL replicability in 87 prostate tissue samples from the Gene-Tissue Expression Project. These findings provide further biological context to known risk loci and outline new hypotheses for investigation into the etiology of prostate cancer.

  10. Automatic classification of prostate stromal tissue in histological images using Haralick descriptors and Local Binary Patterns

    International Nuclear Information System (INIS)

    Oliveira, D L L; Batista, V R; Duarte, Y A S; Nascimento, M Z; Neves, L A; Godoy, M F; Jacomini, R S; Arruda, P F F; Neto, D S

    2014-01-01

    In this paper we presente a classification system that uses a combination of texture features from stromal regions: Haralick features and Local Binary Patterns (LBP) in wavelet domain. The system has five steps for classification of the tissues. First, the stromal regions were detected and extracted using segmentation techniques based on thresholding and RGB colour space. Second, the Wavelet decomposition was applied in the extracted regions to obtain the Wavelet coefficients. Third, the Haralick and LBP features were extracted from the coefficients. Fourth, relevant features were selected using the ANOVA statistical method. The classication (fifth step) was performed with Radial Basis Function (RBF) networks. The system was tested in 105 prostate images, which were divided into three groups of 35 images: normal, hyperplastic and cancerous. The system performance was evaluated using the area under the ROC curve and resulted in 0.98 for normal versus cancer, 0.95 for hyperplasia versus cancer and 0.96 for normal versus hyperplasia. Our results suggest that texture features can be used as discriminators for stromal tissues prostate images. Furthermore, the system was effective to classify prostate images, specially the hyperplastic class which is the most difficult type in diagnosis and prognosis

  11. Preoperative Nomogram Predicting the 10-Year Probability of Prostate Cancer Recurrence After Radical Prostatectomy

    Science.gov (United States)

    Stephenson, Andrew J.; Scardino, Peter T.; Eastham, James A.; Bianco, Fernando J.; Dotan, Zohar A.; Fearn, Paul A.; Kattan, Michael W.

    2008-01-01

    An existing preoperative nomogram predicts the probability of prostate cancer recurrence, defined by prostate-specific antigen (PSA), at 5 years after radical prostatectomy based on clinical stage, serum PSA, and biopsy Gleason grade. In an updated and enhanced nomogram, we have extended the predictions to 10 years, added the prognostic information of systematic biopsy results, and enabled the predictions to be adjusted for the year of surgery. Cox regression analysis was used to model the clinical information for 1978 patients treated by two high-volume surgeons from our institution. The nomogram was externally validated on an independent cohort of 1545 patients with a concordance index of 0.79 and was well calibrated with respect to observed outcome. The inclusion of the number of positive and negative biopsy cores enhanced the predictive accuracy of the model. Thus, a new preoperative nomogram provides robust predictions of prostate cancer recurrence up to 10 years after radical prostatectomy. PMID:16705126

  12. Alteration of proliferation and apoptotic markers in normal and premalignant tissue associated with prostate cancer

    International Nuclear Information System (INIS)

    Ananthanarayanan, Vijayalakshmi; Deaton, Ryan J; Yang, Ximing J; Pins, Michael R; Gann, Peter H

    2006-01-01

    Molecular markers identifying alterations in proliferation and apoptotic pathways could be particularly important in characterizing high-risk normal or pre-neoplastic tissue. We evaluated the following markers: Ki67, Minichromosome Maintenance Protein-2 (Mcm-2), activated caspase-3 (a-casp3) and Bcl-2 to determine if they showed differential expression across progressive degrees of intraepithelial neoplasia and cancer in the prostate. To identify field effects, we also evaluated whether high-risk expression patterns in normal tissue were more common in prostates containing cancer compared to those without cancer (supernormal), and in histologically normal glands adjacent to a cancer focus as opposed to equivalent glands that were more distant. The aforementioned markers were studied in 13 radical prostatectomy (RP) and 6 cystoprostatectomy (CP) specimens. Tissue compartments representing normal, low grade prostatic intraepithelial neoplasia (LGPIN), high grade prostatic intraepithelial neoplasia (HGPIN), as well as different grades of cancer were mapped on H&E slides and adjacent sections were analyzed using immunohistochemistry. Normal glands within 1 mm distance of a tumor focus and glands beyond 5 mm were considered 'near' and 'far', respectively. Randomly selected nuclei and 40 × fields were scored by a single observer; basal and luminal epithelial layers were scored separately. Both Ki-67 and Mcm-2 showed an upward trend from normal tissue through HGPIN and cancer with a shift in proliferation from basal to luminal compartment. Activated caspase-3 showed a significant decrease in HGPIN and cancer compartments. Supernormal glands had significantly lower proliferation indices and higher a-casp3 expression compared to normal glands. 'Near' normal glands had higher Mcm-2 indices compared to 'far' glands; however, they also had higher a-casp3 expression. Bcl-2, which varied minimally in normal tissue, did not show any trend

  13. Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error

    OpenAIRE

    Shipitsin, M; Small, C; Choudhury, S; Giladi, E; Friedlander, S; Nardone, J; Hussain, S; Hurley, A D; Ernst, C; Huang, Y E; Chang, H; Nifong, T P; Rimm, D L; Dunyak, J; Loda, M

    2014-01-01

    Background: Key challenges of biopsy-based determination of prostate cancer aggressiveness include tumour heterogeneity, biopsy-sampling error, and variations in biopsy interpretation. The resulting uncertainty in risk assessment leads to significant overtreatment, with associated costs and morbidity. We developed a performance-based strategy to identify protein biomarkers predictive of prostate cancer aggressiveness and lethality regardless of biopsy-sampling variation. Methods: Prostatectom...

  14. REST mediates androgen receptor actions on gene repression and predicts early recurrence of prostate cancer

    DEFF Research Database (Denmark)

    Svensson, Charlotte; Ceder, Jens; Iglesias Gato, Diego

    2014-01-01

    The androgen receptor (AR) is a key regulator of prostate tumorgenesis through actions that are not fully understood. We identified the repressor element (RE)-1 silencing transcription factor (REST) as a mediator of AR actions on gene repression. Chromatin immunoprecipitation showed that AR binds...... in cell cycle progression, including Aurora Kinase A, that has previously been implicated in the growth of NE-like castration-resistant tumors. The analysis of prostate cancer tissue microarrays revealed that tumors with reduced expression of REST have higher probability of early recurrence, independently...... of their Gleason score. The demonstration that REST modulates AR actions in prostate epithelia and that REST expression is negatively correlated with disease recurrence after prostatectomy, invite a deeper characterization of its role in prostate carcinogenesis....

  15. Epigenomic profiling of DNA methylation in paired prostate cancer versus adjacent benign tissue.

    Science.gov (United States)

    Geybels, Milan S; Zhao, Shanshan; Wong, Chao-Jen; Bibikova, Marina; Klotzle, Brandy; Wu, Michael; Ostrander, Elaine A; Fan, Jian-Bing; Feng, Ziding; Stanford, Janet L

    2015-12-01

    Aberrant DNA methylation may promote prostate carcinogenesis. We investigated epigenome-wide DNA methylation profiles in prostate cancer (PCa) compared to adjacent benign tissue to identify differentially methylated CpG sites. The study included paired PCa and adjacent benign tissue samples from 20 radical prostatectomy patients. Epigenetic profiling was done using the Infinium HumanMethylation450 BeadChip. Linear models that accounted for the paired study design and False Discovery Rate Q-values were used to evaluate differential CpG methylation. mRNA expression levels of the genes with the most differentially methylated CpG sites were analyzed. In total, 2,040 differentially methylated CpG sites were identified in PCa versus adjacent benign tissue (Q-value Cancer Genome Atlas (TCGA) data provided confirmatory evidence for our findings. This study of PCa versus adjacent benign tissue showed many differentially methylated CpGs and regions in and outside gene promoter regions, which may potentially be used for the development of future epigenetic-based diagnostic tests or as therapeutic targets. © 2015 Wiley Periodicals, Inc.

  16. Combination of prostate specific antigen and pathological stage regarding to gleason score to predict bone metastasis of newly diagnosed prostate cancer

    International Nuclear Information System (INIS)

    Wang Zhen; Zhou Liquan; Gao Jiangping; Shi Lixin; Zhao Xiaoyi; Hong Baofa

    2004-01-01

    To determine the value of tumor grade and serum prostate-specific antigen in predicting skeletal metastases in untreated prostate cancer, the results of bone scans were related retrospectively to levels of serum PSA and tumor Grade based on pathologyical examination in 202 patients with prostate cancer newly diagnosed. Skeletal metastases were present in 7% of patients with serum PSA 100 μg/L. Bone scans are omitted likely in a man newly diagnosed with prostate cancer who has no suggestive clinical features, a serum PSA 100 μg/L. (authors)

  17. Prediction of extraprostatic extension by prostate specific antigen velocity, endorectal MRI, and biopsy Gleason score in clinically localized prostate cancer

    International Nuclear Information System (INIS)

    Nishimoto, Koshiro; Nakashima, Jun; Hashiguchi, Akinori; Kikuchi, Eiji; Miyajima, Akira; Nakagawa, Ken; Ohigashi, Takashi; Oya, Mototsugu; Murai, Masaru

    2008-01-01

    The objective of this study was to investigate the clinical value of prostate specific antigen velocity (PSAV) in predicting the extraprostatic extension of clinically localized prostate cancer. One hundred and three patients who underwent radical prostatectomy for clinically localized prostate cancer were included in the analysis. The correlation between preoperative parameters, including PSA-based parameters, clinical stage, and histological biopsy findings, and the pathological findings were analyzed. Logistic regression analysis was performed to identify a significant set of independent predictors for the local extent of the disease. Sixty-four (60.2%) patients had organ confined prostate cancer and 39 (39.8%) patients had extraprostatic cancer. The biopsy Gleason score, PSA, PSA density, PSA density of the transition zone, and PSAV were significantly higher in the patients with extraprostatic cancer than in those with organ confined cancer. Multivariate logistic regression analysis indicated that the biopsy Gleason score, endorectal magnetic resonance imaging findings, and PSAV were significant predictors of extraprostatic cancer (P<0.01). Probability curves for extraprostatic cancer were generated using these three preoperative parameters. The combination of PSAV, endorectal magnetic resonance imaging findings, and biopsy Gleason score can provide additional information for selecting appropriate candidates for radical prostatectomy. (author)

  18. Re-examining Prostate-specific Antigen (PSA) Density: Defining the Optimal PSA Range and Patients for Using PSA Density to Predict Prostate Cancer Using Extended Template Biopsy.

    Science.gov (United States)

    Jue, Joshua S; Barboza, Marcelo Panizzutti; Prakash, Nachiketh S; Venkatramani, Vivek; Sinha, Varsha R; Pavan, Nicola; Nahar, Bruno; Kanabur, Pratik; Ahdoot, Michael; Dong, Yan; Satyanarayana, Ramgopal; Parekh, Dipen J; Punnen, Sanoj

    2017-07-01

    To compare the predictive accuracy of prostate-specific antigen (PSA) density vs PSA across different PSA ranges and by prior biopsy status in a prospective cohort undergoing prostate biopsy. Men from a prospective trial underwent an extended template biopsy to evaluate for prostate cancer at 26 sites throughout the United States. The area under the receiver operating curve assessed the predictive accuracy of PSA density vs PSA across 3 PSA ranges (10 ng/mL). We also investigated the effect of varying the PSA density cutoffs on the detection of cancer and assessed the performance of PSA density vs PSA in men with or without a prior negative biopsy. Among 1290 patients, 585 (45%) and 284 (22%) men had prostate cancer and significant prostate cancer, respectively. PSA density performed better than PSA in detecting any prostate cancer within a PSA of 4-10 ng/mL (area under the receiver operating characteristic curve [AUC]: 0.70 vs 0.53, P PSA >10 mg/mL (AUC: 0.84 vs 0.65, P PSA density was significantly more predictive than PSA in detecting any prostate cancer in men without (AUC: 0.73 vs 0.67, P PSA increases, PSA density becomes a better marker for predicting prostate cancer compared with PSA alone. Additionally, PSA density performed better than PSA in men with a prior negative biopsy. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. In vivo cryoablation of prostate tissue with temperature monitoring by optoacoustic imaging

    Science.gov (United States)

    Petrova, Elena V.; Motamedi, Massoud; Oraevsky, Alexander A.; Ermilov, Sergey A.

    2016-03-01

    Cryoablation of prostate cancer is an FDA approved clinical procedure, which involves repetitive rapid cooling of a lesion to lethal temperatures of -40°C and below. The major drawback of the technique is the insufficient control over the fast thermal processes that may result in severe complications (impotence, incontinence, perforation of the rectal wall) and morbidity. The developed optoacoustic imaging technique provides non-invasive real-time temperature mapping of tissue adjacent to prostate and enables more efficient control over the procedure, which is necessary to reduce side effects and accelerate the physician's learning curve. In these studies we successfully demonstrated real-time transrectal optoacoustic imaging during prostate cryoablation in live canine model focused on optoacoustic thermography of the rectal wall within the depth of 1cm. Our method utilized previously discovered universal thermal dependence of the normalized optoacoustic response of blood. Nanosecond-pulse radiation of Ti-Sapphire laser tuned to the isosbestic point of hemoglobin (802+/-3 nm) was delivered via fiberoptic illuminators assembled on both sides of the linear array of the 128-channel transrectal ultrasound probe. Temperature readouts at discrete locations inside and nearby prostate were also performed using standard transperineal needle sensors. The effect of homeostasis on optoacoustic imaging in live tissue was examined during cooling and shown to be significant only within the range of +/-1.5°C in respect to the body temperature. Accuracy of in vivo optoacoustic temperature measurements was determined as +/-2°C for the range of temperature from +35 to -15°C, which is more than sufficient for tracking the essential isotherms in the course of clinical procedures.

  20. LINE-1 methylation status in prostate cancer and non-neoplastic tissue adjacent to tumor in association with mortality.

    Science.gov (United States)

    Fiano, Valentina; Zugna, Daniela; Grasso, Chiara; Trevisan, Morena; Delsedime, Luisa; Molinaro, Luca; Gillio-Tos, Anna; Merletti, Franco; Richiardi, Lorenzo

    2017-01-02

    Aberrant DNA methylation seems to be associated with prostate cancer behavior. We investigated LINE-1 methylation in prostate cancer and non-neoplastic tissue adjacent to tumor (NTAT) in association with mortality from prostate cancer. We selected 157 prostate cancer patients with available NTAT from 2 cohorts of patients diagnosed between 1982-1988 and 1993-1996, followed up until 2010. An association between LINE-1 hypomethylation and prostate cancer mortality in tumor was suggested [hazard ratio per 5% decrease in LINE-1 methylation levels: 1.40, 95% confidence interval (CI): 0.95-2.01]. After stratification of the patients for Gleason score, the association was present only for those with a Gleason score of at least 8. Among these, low (80%) LINE-1 methylation was associated with a hazard ratio of 4.68 (95% CI: 1.03-21.34). LINE-1 methylation in the NTAT was not associated with prostate cancer mortality. Our results are consistent with the hypothesis that tumor tissue global hypomethylation may be a late event in prostate cancerogenesis and is associated with tumor progression.

  1. Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.

    Science.gov (United States)

    Cooper, Colin S; Eeles, Rosalind; Wedge, David C; Van Loo, Peter; Gundem, Gunes; Alexandrov, Ludmil B; Kremeyer, Barbara; Butler, Adam; Lynch, Andrew G; Camacho, Niedzica; Massie, Charlie E; Kay, Jonathan; Luxton, Hayley J; Edwards, Sandra; Kote-Jarai, ZSofia; Dennis, Nening; Merson, Sue; Leongamornlert, Daniel; Zamora, Jorge; Corbishley, Cathy; Thomas, Sarah; Nik-Zainal, Serena; O'Meara, Sarah; Matthews, Lucy; Clark, Jeremy; Hurst, Rachel; Mithen, Richard; Bristow, Robert G; Boutros, Paul C; Fraser, Michael; Cooke, Susanna; Raine, Keiran; Jones, David; Menzies, Andrew; Stebbings, Lucy; Hinton, Jon; Teague, Jon; McLaren, Stuart; Mudie, Laura; Hardy, Claire; Anderson, Elizabeth; Joseph, Olivia; Goody, Victoria; Robinson, Ben; Maddison, Mark; Gamble, Stephen; Greenman, Christopher; Berney, Dan; Hazell, Steven; Livni, Naomi; Fisher, Cyril; Ogden, Christopher; Kumar, Pardeep; Thompson, Alan; Woodhouse, Christopher; Nicol, David; Mayer, Erik; Dudderidge, Tim; Shah, Nimish C; Gnanapragasam, Vincent; Voet, Thierry; Campbell, Peter; Futreal, Andrew; Easton, Douglas; Warren, Anne Y; Foster, Christopher S; Stratton, Michael R; Whitaker, Hayley C; McDermott, Ultan; Brewer, Daniel S; Neal, David E

    2015-04-01

    Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases.

  2. Differentially expressed androgen-regulated genes in androgen-sensitive tissues reveal potential biomarkers of early prostate cancer.

    Directory of Open Access Journals (Sweden)

    Dogus Murat Altintas

    Full Text Available BACKGROUND: Several data favor androgen receptor implication in prostate cancer initiation through the induction of several gene activation programs. The aim of the study is to identify potential biomarkers for early diagnosis of prostate cancer (PCa among androgen-regulated genes (ARG and to evaluate comparative expression of these genes in normal prostate and normal prostate-related androgen-sensitive tissues that do not (or rarely give rise to cancer. METHODS: ARG were selected in non-neoplastic adult human prostatic epithelial RWPE-1 cells stably expressing an exogenous human androgen receptor, using RNA-microarrays and validation by qRT-PCR. Expression of 48 preselected genes was quantified in tissue samples (seminal vesicles, prostate transitional zones and prostate cancers, benign prostatic hypertrophy obtained from surgical specimens using TaqMan® low-density arrays. The diagnostic performances of these potential biomarkers were compared to that of genes known to be associated with PCa (i.e. PCA3 and DLX1. RESULTS AND DISCUSSION: By crossing expression studies in 26 matched PCa and normal prostate transitional zone samples, and 35 matched seminal vesicle and PCa samples, 14 genes were identified. Similarly, 9 genes were overexpressed in 15 benign prostatic hypertrophy samples, as compared to PCa samples. Overall, we selected 8 genes of interest to evaluate their diagnostic performances in comparison with that of PCA3 and DLX1. Among them, 3 genes: CRYAB, KCNMA1 and SDPR, were overexpressed in all 3 reference non-cancerous tissues. The areas under ROC curves of these genes reached those of PCA3 (0.91 and DLX1 (0.94. CONCLUSIONS: We identified ARG with reduced expression in PCa and with significant diagnostic values for discriminating between cancerous and non-cancerous prostatic tissues, similar that of PCA3. Given their expression pattern, they could be considered as potentially protective against prostate cancer. Moreover, they could

  3. MRI to predict prostate growth and development in children, adolescents and young adults.

    Science.gov (United States)

    Ren, Jing; Liu, Huijia; Wang, He; Wen, Didi; Huang, Xufang; Ren, Fang; Huan, Yi

    2015-02-01

    The purpose of this study was to investigate the use of MRI in predicting prostate growth and development. A total of 1,500 healthy male volunteers who underwent MRI of the pelvis were included in this prospective study. Subjects were divided into five groups according to age (group A, 2-5 years; group B, 6-10 years; group C, 11-15 years; group D, 16-20 years; group E, 21-25 years). Total prostate volume (TPV) as well as prostate central zone (CZ) and peripheral zone (PZ) were measured and evaluated on MRI. Data of the different groups were compared using variance analysis, Scheffé's method, Kruskal-Wallis H-test, and Pearson's correlation. Statistical significance was inferred at P development scores were 0.08, 0.69, 1.56, 2.38, and 2.74, respectively. Both TPVs and zonal anatomy scores varied significantly among the five groups (P = 0.000). TPV and zonal anatomy score increased with increasing age. MRI provides a reliable quantitative reference for prostate growth and development. • When and how the prostate develops after birth remains unclear. • Prostate volume increases rapidly after the age of 10 years. • MRI provides a reliable objective and quantitative reference for prostate growth and development.

  4. Protein Profiling of Isolated Leukocytes, Myofibroblasts, Epithelial, Basal, and Endothelial Cells from Normal, Hyperplastic, Cancerous, and Inflammatory Human Prostate Tissues

    Directory of Open Access Journals (Sweden)

    Zahraa I. Khamis, Kenneth A. Iczkowski, Ziad J. Sahab, Qing-Xiang Amy Sang

    2010-01-01

    Full Text Available In situ neoplastic prostate cells are not lethal unless they become invasive and metastatic. For cells to become invasive, the prostate gland must undergo degradation of the basement membrane and disruption of the basal cell layer underneath the luminal epithelia. Although the roles of proteinases in breaking down the basement membrane have been well-studied, little is known about the factors that induce basal cell layer disruption, degeneration, and its eventual disappearance in invasive cancer. It is hypothesized that microenvironmental factors may affect the degradation of the basal cell layer, which if protected may prevent tumor progression and invasion. In this study, we have revealed differential protein expression patterns between epithelial and stromal cells isolated from different prostate pathologies and identified several important epithelial and stromal proteins that may contribute to inflammation and malignant transformation of human benign prostate tissues to cancerous tissues using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and proteomics methods. Cellular retinoic acid-binding protein 2 was downregulated in basal cells of benign prsotate. Caspase-1 and interleukin-18 receptor 1 were highly expressed in leukocytes of prostate cancer. Proto-oncogene Wnt-3 was downregulated in endothelial cells of prostatitis tissue and tyrosine phosphatase non receptor type 1 was only found in normal and benign endothelial cells. Poly ADP-ribose polymerase 14 was downregulated in myofibroblasts of prostatitis tissue. Interestingly, integrin alpha-6 was upregulated in epithelial cells but not detected in myofibroblasts of prostate cancer. Further validation of these proteins may generate new strategies for the prevention of basal cell layer disruption and subsequent cancer invasion.

  5. Dosimetric Coverage of the Prostate, Normal Tissue Sparing, and Acute Toxicity with High-Dose-Rate Brachytherapy for Large Prostate Volumes

    Directory of Open Access Journals (Sweden)

    George Yang

    2015-06-01

    Full Text Available ABSTRACTPurposeTo evaluate dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with HDR brachytherapy for large prostate volumes.Materials and MethodsOne hundred and two prostate cancer patients with prostate volumes >50 mL (range: 5-29 mL were treated with high-dose-rate (HDR brachytherapy ± intensity modulated radiation therapy (IMRT to 4,500 cGy in 25 daily fractions between 2009 and 2013. HDR brachytherapy monotherapy doses consisted of two 1,350-1,400 cGy fractions separated by 2-3 weeks, and HDR brachytherapy boost doses consisted of two 950-1,150 cGy fractions separated by 4 weeks. Twelve of 32 (38% unfavorable intermediate risk, high risk, and very high risk patients received androgen deprivation therapy. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.ResultsMedian follow-up was 14 months. Dosimetric goals were achieved in over 90% of cases. Three of 102 (3% patients developed Grade 2 acute proctitis. No variables were significantly associated with Grade 2 acute proctitis. Seventeen of 102 (17% patients developed Grade 2 acute urinary retention. American Urological Association (AUA symptom score was the only variable significantly associated with Grade 2 acute urinary retention (p=0.04. There was no ≥ Grade 3 acute toxicity.ConclusionsDosimetric coverage of the prostate and normal tissue sparing were adequate in patients with prostate volumes >50 mL. Higher pre-treatment AUA symptom scores increased the relative risk of Grade 2 acute urinary retention. However, the overall incidence of acute toxicity was acceptable in patients with large prostate volumes.

  6. Dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with high-dose-rate brachytherapy for large prostate volumes

    Energy Technology Data Exchange (ETDEWEB)

    Yang, George; Strom, Tobin J.; Shrinath, Kushagra; Mellon, Eric A.; Fernandez, Daniel C.; Biagioli, Matthew C. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States); Wilder, Richard B., E-mail: mcbiagioli@yahoo.com [Cancer Treatment Centers of America, Newnan, GA (United States)

    2015-05-15

    Purpose: to evaluate dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with HDR brachytherapy for large prostate volumes. Materials and methods: one hundred and two prostate cancer patients with prostate volumes >50 mL (range: 5-29 mL) were treated with high-dose-rate (HDR) brachytherapy ± intensity modulated radiation therapy (IMRT) to 4,500 cGy in 25 daily fractions between 2009 and 2013. HDR brachytherapy monotherapy doses consisted of two 1,350-1,400 cGy fractions separated by 2-3 weeks, and HDR brachytherapy boost doses consisted of two 950-1,150 cGy fractions separated by 4 weeks. Twelve of 32 (38%) unfavorable intermediate risk, high risk, and very high risk patients received androgen deprivation therapy. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4. Results: median follow-up was 14 months. Dosimetric goals were achieved in over 90% of cases. Three of 102 (3%) patients developed Grade 2 acute proctitis. No variables were significantly associated with Grade 2 acute proctitis. Seventeen of 102 (17%) patients developed Grade 2 acute urinary retention. American Urological Association (AUA) symptom score was the only variable significantly associated with Grade 2 acute urinary retention (p-0.04). There was no ≥ Grade 3 acute toxicity. Conclusions: dosimetric coverage of the prostate and normal tissue sparing were adequate in patients with prostate volumes >50 mL. Higher pre-treatment AUA symptom scores increased the relative risk of Grade 2 acute urinary retention. However, the overall incidence of acute toxicity was acceptable in patients with large prostate volumes. (author)

  7. Evaluation of Zinc-alpha-2-Glycoprotein and Proteasome Subunit beta-Type 6 Expression in Prostate Cancer Using Tissue Microarray Technology.

    LENUS (Irish Health Repository)

    2010-07-23

    Prostate cancer (CaP) is a significant cause of illness and death in males. Current detection strategies do not reliably detect the disease at an early stage and cannot distinguish aggressive versus nonaggressive CaP leading to potential overtreatment of the disease and associated morbidity. Zinc-alpha-2-glycoprotein (ZAG) and proteasome subunit beta-Type 6 (PSMB-6) were found to be up-regulated in the serum of CaP patients with higher grade tumors after 2-dimensional difference gel electrophoresis analysis. The aim of this study was to investigate if ZAG and PSMB-6 were also overexpressed in prostatic tumor tissue of CaP patients. Immunohistochemical analysis was performed on CaP tissue microarrays with samples from 199 patients. Confirmatory gene expression profiling for ZAG and PSMB-6 were performed on 4 cases using Laser Capture Microdissection and TaqMan real-time polymerase chain reaction. ZAG expression in CaP epithelial cells was inversely associated with Gleason grade (benign prostatic hyperplasia>G3>G4\\/G5). PSMB-6 was not expressed in either tumor or benign epithelium. However, strong PSMB-6 expression was noted in stromal and inflammatory cells. Our results indicate ZAG as a possible predictive marker of Gleason grade. The inverse association between grade and tissue expression with a rising serum protein level is similar to that seen with prostate-specific antigen. In addition, the results for both ZAG and PSMB-6 highlight the challenges in trying to associate the protein levels in serum with tissue expression.

  8. Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression.

    Directory of Open Access Journals (Sweden)

    Irene Forno

    Full Text Available Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was associated with epigenetics silencing of the MIR34B/C locus and increased DNA copy number loss, selectively in androgen-dependent prostate cancer. In turn, loss of miR-34b resulted in downstream deregulation and overexpression of the "stemness" marker, Sox2. These findings identify loss of miR-34b as a robust biomarker for prostate cancer progression in androgen-sensitive tumors, and anticipate a potential role of progenitor/stem cell signaling in this stage of disease.

  9. Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression.

    Science.gov (United States)

    Forno, Irene; Ferrero, Stefano; Russo, Maria Veronica; Gazzano, Giacomo; Giangiobbe, Sara; Montanari, Emanuele; Del Nero, Alberto; Rocco, Bernardo; Albo, Giancarlo; Languino, Lucia R; Altieri, Dario C; Vaira, Valentina; Bosari, Silvano

    2015-01-01

    Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was associated with epigenetics silencing of the MIR34B/C locus and increased DNA copy number loss, selectively in androgen-dependent prostate cancer. In turn, loss of miR-34b resulted in downstream deregulation and overexpression of the "stemness" marker, Sox2. These findings identify loss of miR-34b as a robust biomarker for prostate cancer progression in androgen-sensitive tumors, and anticipate a potential role of progenitor/stem cell signaling in this stage of disease.

  10. Prostate Ultrasound

    Medline Plus

    Full Text Available ... uses sound waves to produce pictures of a man’s prostate gland and to help diagnose symptoms such ... also called transrectal ultrasound, provides images of a man's prostate gland and surrounding tissue. The exam typically ...

  11. Does Inflammation Mediate the Obesity and BPH Relationship? An Epidemiologic Analysis of Body Composition and Inflammatory Markers in Blood, Urine, and Prostate Tissue, and the Relationship with Prostate Enlargement and Lower Urinary Tract Symptoms.

    Science.gov (United States)

    Fowke, Jay H; Koyama, Tatsuki; Fadare, Oluwole; Clark, Peter E

    2016-01-01

    BPH is a common disease associated with age and obesity. However, the biological pathways between obesity and BPH are unknown. Our objective was to investigate biomarkers of systemic and prostate tissue inflammation as potential mediators of the obesity and BPH association. Participants included 191 men without prostate cancer at prostate biopsy. Trained staff measured weight, height, waist and hip circumferences, and body composition by bioelectric impedance analysis. Systemic inflammation was estimated by serum IL-6, IL-1β, IL-8, and TNF-α; and by urinary prostaglandin E2 metabolite (PGE-M), F2-isoprostane (F2iP), and F2-isoprostane metabolite (F2iP-M) levels. Prostate tissue was scored for grade, aggressiveness, extent, and location of inflammatory regions, and also stained for CD3 and CD20 positive lymphocytes. Analyses investigated the association between multiple body composition scales, systemic inflammation, and prostate tissue inflammation against BPH outcomes, including prostate size at ultrasound and LUTS severity by the AUA-symptom index (AUA-SI). Prostate size was significantly associated with all obesity measures. For example, prostate volume was 5.5 to 9.0 mls larger comparing men in the 25th vs. 75th percentile of % body fat, fat mass (kg) or lean mass (kg). However, prostate size was not associated with proinflammatory cytokines, PGE-M, F2iP, F2iP-M, prostate tissue inflammation scores or immune cell infiltration. In contrast, the severity of prostate tissue inflammation was significantly associated with LUTS, such that there was a 7 point difference in AUA-SI between men with mild vs. severe inflammation (p = 0.004). Additionally, men with a greater waist-hip ratio (WHR) were significantly more likely to have severe prostate tissue inflammation (p = 0.02), and a high WHR was significantly associated with moderate/severe LUTS (OR = 2.56, p = 0.03) among those participants with prostate tissue inflammation. The WHR, an estimate of centralized

  12. [Circulating miR-152 helps early prediction of postoperative biochemical recurrence of prostate cancer].

    Science.gov (United States)

    Chen, Jun-Feng; Liao, Yu-Feng; Ma, Jian-Bo; Mao, Qi-Feng; Jia, Guang-Cheng; Dong, Xue-Jun

    2017-07-01

    To investigate the value of circulating miR-152 in the early prediction of postoperative biochemical recurrence of prostate cancer. Sixty-six cases of prostate cancer were included in this study, 35 with and 31 without biochemical recurrence within two years postoperatively, and another 31 healthy individuals were enrolled as normal controls. The relative expression levels of circulating miR-152 in the serum of the subjects were detected by qRT-PCR, its value in the early diagnosis of postoperative biochemical recurrence of prostate cancer was assessed by ROC curve analysis, and the correlation of its expression level with the clinicopathological parameters of the patients were analyzed. The expression of circulating miR-152 was significantly lower in the serum of the prostate cancer patients than in the normal controls (t = -5.212, P = 0.001), and so was it in the patients with than in those without postoperative biochemical recurrence (t = -5.727, P = 0.001). The ROC curve for the value of miR-152 in the early prediction of postoperative biochemical recurrence of prostate cancer showed the area under the curve (AUC) to be 0.906 (95% CI: 0.809-0.964), with a sensitivity of 91.4% and a specificity of 80.6%. The expression level of miR-152 was correlated with the Gleason score, clinical stage of prostate cancer, biochemical recurrence, and bone metastasis (P 0.05). The expression level of circulating miR-152 is significantly reduced in prostate cancer patients with biochemical recurrence after prostatectomy and could be a biomarker in the early prediction of postoperative biochemical recurrence of the malignancy.

  13. Prediction of prostate cancer in unscreened men: external validation of a risk calculator.

    Science.gov (United States)

    van Vugt, Heidi A; Roobol, Monique J; Kranse, Ries; Määttänen, Liisa; Finne, Patrik; Hugosson, Jonas; Bangma, Chris H; Schröder, Fritz H; Steyerberg, Ewout W

    2011-04-01

    Prediction models need external validation to assess their value beyond the setting where the model was derived from. To assess the external validity of the European Randomized study of Screening for Prostate Cancer (ERSPC) risk calculator (www.prostatecancer-riskcalculator.com) for the probability of having a positive prostate biopsy (P(posb)). The ERSPC risk calculator was based on data of the initial screening round of the ERSPC section Rotterdam and validated in 1825 and 531 men biopsied at the initial screening round in the Finnish and Swedish sections of the ERSPC respectively. P(posb) was calculated using serum prostate specific antigen (PSA), outcome of digital rectal examination (DRE), transrectal ultrasound and ultrasound assessed prostate volume. The external validity was assessed for the presence of cancer at biopsy by calibration (agreement between observed and predicted outcomes), discrimination (separation of those with and without cancer), and decision curves (for clinical usefulness). Prostate cancer was detected in 469 men (26%) of the Finnish cohort and in 124 men (23%) of the Swedish cohort. Systematic miscalibration was present in both cohorts (mean predicted probability 34% versus 26% observed, and 29% versus 23% observed, both pscreened men, but overestimated the risk of a positive biopsy. Further research is necessary to assess the performance and applicability of the ERSPC risk calculator when a clinical setting is considered rather than a screening setting. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. Metabolomic profiling of lung and prostate tumor tissues by capillary electrophoresis time-of-flight mass spectrometry.

    Science.gov (United States)

    Kami, Kenjiro; Fujimori, Tamaki; Sato, Hajime; Sato, Mutsuko; Yamamoto, Hiroyuki; Ohashi, Yoshiaki; Sugiyama, Naoyuki; Ishihama, Yasushi; Onozuka, Hiroko; Ochiai, Atsushi; Esumi, Hiroyasu; Soga, Tomoyoshi; Tomita, Masaru

    2013-04-01

    Metabolic microenvironment of tumor cells is influenced by oncogenic signaling and tissue-specific metabolic demands, blood supply, and enzyme expression. To elucidate tumor-specific metabolism, we compared the metabolomics of normal and tumor tissues surgically resected pairwise from nine lung and seven prostate cancer patients, using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Phosphorylation levels of enzymes involved in central carbon metabolism were also quantified. Metabolomic profiles of lung and prostate tissues comprised 114 and 86 metabolites, respectively, and the profiles not only well distinguished tumor from normal tissues, but also squamous cell carcinoma from the other tumor types in lung cancer and poorly differentiated tumors from moderately differentiated tumors in prostate cancer. Concentrations of most amino acids, especially branched-chain amino acids, were significantly higher in tumor tissues, independent of organ type, but of essential amino acids were particularly higher in poorly differentiated than moderately differentiated prostate cancers. Organ-dependent differences were prominent at the levels of glycolytic and tricarboxylic acid cycle intermediates and associated energy status. Significantly high lactate concentrations and elevated activating phosphorylation levels of phosphofructokinase and pyruvate kinase in lung tumors confirmed hyperactive glycolysis. We highlighted the potential of CE-TOFMS-based metabolomics combined with phosphorylated enzyme analysis for understanding tissue-specific tumor microenvironments, which may lead to the development of more effective and specific anticancer therapeutics.

  15. Increased Expression of Herpes Virus-Encoded hsv1-miR-H18 and hsv2-miR-H9-5p in Cancer-Containing Prostate Tissue Compared to That in Benign Prostate Hyperplasia Tissue

    Directory of Open Access Journals (Sweden)

    Seok Joong Yun

    2016-06-01

    Full Text Available Purpose: Previously, we reported the presence of virus-encoded microRNAs (miRNAs in the urine of prostate cancer (CaP patients. In this study, we investigated the expression of two herpes virus-encoded miRNAs in prostate tissue. Methods: A total of 175 tissue samples from noncancerous benign prostatic hyperplasia (BPH, 248 tissue samples from patients with CaP and BPH, and 50 samples from noncancerous surrounding tissues from these same patients were analyzed for the expression of two herpes virus-encoded miRNAs by real-time polymerase chain reaction (PCR and immunocytochemistry using nanoparticles as molecular beacons. Results: Real-time reverse transcription-PCR results revealed significantly higher expression of hsv1-miR-H18 and hsv2-miRH9- 5p in surrounding noncancerous and CaP tissues than that in BPH tissue (each comparison, P<0.001. Of note, these miRNA were expressed equivalently in the CaP tissues and surrounding noncancerous tissues. Moreover, immunocytochemistry clearly demonstrated a significant enrichment of both hsv1-miR-H18 and hsv2-miR-H9 beacon-labeled cells in CaP and surrounding noncancerous tissue compared to that in BPH tissue (each comparison, P<0.05 for hsv1-miR-H18 and hsv2- miR-H9. Conclusions: These results suggest that increased expression of hsv1-miR-H18 and hsv2-miR-H95p might be associated with tumorigenesis in the prostate. Further studies will be required to elucidate the role of these miRNAs with respect to CaP and herpes viral infections.

  16. Correlation between Microvascular Density and Matrix Metalloproteinase 11 Expression in Prostate Cancer Tissues: a Preliminary Study in Thailand.

    Science.gov (United States)

    Kanharat, Nongnuch; Tuamsuk, Panya

    2015-01-01

    Prostate cancer is a major concern of public health. Microvascular density (MVD) is one of the prognostic markers for various solid cancers. Matrix metalloproteinase 11 (MMP11) plays an important role in angiogenesis and changes in its expression level are known to be associated with tumor progression and clinical outcome. To investigate the relationship between MVD and MMP11 expression in prostatic adenocarcinoma tissues. The expression levels of MMP11 and MVD were analyzed immunohistochemically for 50 specimens of prostatic adenocarcinoma. MMP11 was mainly expressed in stromal cells but rarely seen in epithelial cells. Mean MVD was 36/mm2, and it was correlated significantly only with bone metastases. MVD was also significantly correlated with MMP11 expression (r=0.29, p=0.044). MMP11 may alter the stromal microenvironment of prostate cancer to stimulate tumor angiogenesis.

  17. Automated segmentation of reference tissue for prostate cancer localization in dynamic contrast enhanced MRI

    Science.gov (United States)

    Vos, Pieter C.; Hambrock, Thomas; Barentsz, Jelle O.; Huisman, Henkjan J.

    2010-03-01

    For pharmacokinetic (PK) analysis of Dynamic Contrast Enhanced (DCE) MRI the arterial input function needs to be estimated. Previously, we demonstrated that PK parameters have a significant better discriminative performance when per patient reference tissue was used, but required manual annotation of reference tissue. In this study we propose a fully automated reference tissue segmentation method that tackles this limitation. The method was tested with our Computer Aided Diagnosis (CADx) system to study the effect on the discriminating performance for differentiating prostate cancer from benign areas in the peripheral zone (PZ). The proposed method automatically segments normal PZ tissue from DCE derived data. First, the bladder is segmented in the start-to-enhance map using the Otsu histogram threshold selection method. Second, the prostate is detected by applying a multi-scale Hessian filter to the relative enhancement map. Third, normal PZ tissue was segmented by threshold and morphological operators. The resulting segmentation was used as reference tissue to estimate the PK parameters. In 39 consecutive patients carcinoma, benign and normal tissue were annotated on MR images by a radiologist and a researcher using whole mount step-section histopathology as reference. PK parameters were computed for each ROI. Features were extracted from the set of ROIs using percentiles to train a support vector machine that was used as classifier. Prospective performance was estimated by means of leave-one-patient-out cross validation. A bootstrap resampling approach with 10,000 iterations was used for estimating the bootstrap mean AUCs and 95% confidence intervals. In total 42 malignant, 29 benign and 37 normal regions were annotated. For all patients, normal PZ was successfully segmented. The diagnostic accuracy obtained for differentiating malignant from benign lesions using a conventional general patient plasma profile showed an accuracy of 0.64 (0.53-0.74). Using the

  18. Prostate cancer risk prediction based on complete prostate cancer family history

    OpenAIRE

    Albright, Frederick; Stephenson, Robert A; Agarwal, Neeraj; Teerlink, Craig C; Lowrance, William T; Farnham, James M; Albright, Lisa A Cannon

    2014-01-01

    Background Prostate cancer (PC) relative risks (RRs) are typically estimated based on status of close relatives or presence of any affected relatives. This study provides RR estimates using extensive and specific PC family history. Methods A retrospective population-based study was undertaken to estimate RRs for PC based on complete family history of PC. A total of 635,443 males, all with ancestral genealogy data, were analyzed. RRs for PC were determined based upon PC rates estimated from ma...

  19. Data Mining of Small RNA-Seq Suggests an Association Between Prostate Cancer and Altered Abundance of 5′ Transfer RNA Halves in Seminal Fluid and Prostatic Tissues

    Directory of Open Access Journals (Sweden)

    Joseph M Dhahbi

    2018-02-01

    Full Text Available Extracellular RNAs are gaining clinical interest as biofluid-based noninvasive markers for diseases, especially cancer. In particular, derivatives of transfer RNA (tRNA are emerging as a new class of small-noncoding RNAs with high biomarker potential. We and others previously reported alterations in serum levels of specific tRNA halves in disease states including cancer. Here, we explored seminal fluid for tRNA halves as potential markers of prostate cancer. We found that 5′ tRNA halves are abundant in seminal fluid and are elevated in prostate cancer relative to noncancer patients. Importantly, most of these tRNA halves are also detectable in prostatic tissues, and a subset were increased in malignant relative to adjacent normal tissue. These findings emphasize the potential of 5′ tRNA halves as noninvasive markers for prostate cancer screening and diagnosis and provide leads for future work to elucidate a putative role of the 5′ tRNA halves in carcinogenesis.

  20. Development of Castration Resistant Prostate Cancer can be Predicted by a DNA Hypermethylation Profile.

    Science.gov (United States)

    Angulo, Javier C; Andrés, Guillermo; Ashour, Nadia; Sánchez-Chapado, Manuel; López, Jose I; Ropero, Santiago

    2016-03-01

    Detection of DNA hypermethylation has emerged as a novel molecular biomarker for prostate cancer diagnosis and evaluation of prognosis. We sought to define whether a hypermethylation profile of patients with prostate cancer on androgen deprivation would predict castrate resistant prostate cancer. Genome-wide methylation analysis was performed using a methylation cancer panel in 10 normal prostates and 45 tumor samples from patients placed on androgen deprivation who were followed until castrate resistant disease developed. Castrate resistant disease was defined according to EAU (European Association of Urology) guideline criteria. Two pathologists reviewed the Gleason score, Ki-67 index and neuroendocrine differentiation. Hierarchical clustering analysis was performed and relationships with outcome were investigated by Cox regression and log rank analysis. We found 61 genes that were significantly hypermethylated in greater than 20% of tumors analyzed. Three clusters of patients were characterized by a DNA methylation profile, including 1 at risk for earlier castrate resistant disease (log rank p = 0.019) and specific mortality (log rank p = 0.002). Hypermethylation of ETV1 (HR 3.75) and ZNF215 (HR 2.89) predicted disease progression despite androgen deprivation. Hypermethylation of IRAK3 (HR 13.72), ZNF215 (HR 4.81) and SEPT9 (HR 7.64) were independent markers of prognosis. Prostate specific antigen greater than 25 ng/ml, Gleason pattern 5, Ki-67 index greater than 12% and metastasis at diagnosis also predicted a negative response to androgen deprivation. Study limitations included the retrospective design and limited number of cases. Epigenetic silencing of the mentioned genes could be novel molecular markers for the prognosis of advanced prostate cancer. It might predict castrate resistance during hormone deprivation and, thus, disease specific mortality. Gene hypermethylation is associated with disease progression in patients who receive hormone therapy. It

  1. Factors Predicting a Good Symptomatic Outcome After Prostate Artery Embolisation (PAE).

    Science.gov (United States)

    Maclean, D; Harris, M; Drake, T; Maher, B; Modi, S; Dyer, J; Somani, B; Hacking, N; Bryant, T

    2018-02-26

    As prostate artery embolisation (PAE) becomes an established treatment for benign prostatic obstruction, factors predicting good symptomatic outcome remain unclear. Pre-embolisation prostate size as a predictor is controversial with a handful of papers coming to conflicting conclusions. We aimed to investigate if an association existed in our patient cohort between prostate size and clinical benefit, in addition to evaluating percentage volume reduction as a predictor of symptomatic outcome following PAE. Prospective follow-up of 86 PAE patients at a single institution between June 2012 and January 2016 was conducted (mean age 64.9 years, range 54-80 years). Multiple linear regression analysis was performed to assess strength of association between clinical improvement (change in IPSS) and other variables, of any statistical correlation, through Pearson's bivariate analysis. No major procedural complications were identified and clinical success was achieved in 72.1% (n = 62) at 12 months. Initial prostate size and percentage reduction were found to have a significant association with clinical improvement. Multiple linear regression analysis (r 2  = 0.48) demonstrated that percentage volume reduction at 3 months (r = 0.68, p < 0.001) had the strongest correlation with good symptomatic improvement at 12 months after adjusting for confounding factors. Both the initial prostate size and percentage volume reduction at 3 months predict good symptomatic outcome at 12 months. These findings therefore aid patient selection and counselling to achieve optimal outcomes for men undergoing prostate artery embolisation.

  2. MOLECULAR BIOLOGICAL FACTORS IN THE PREDICTION OF PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    S. V. Vtorushin

    2017-01-01

    Full Text Available Purpose: to review the available data on molecular-genetic diagnostic and prognostic markers in prostate cancer. Material and methods. The following electronic databases were used for our systematic review: Medline, Cochrane Library and Elibrary. Of 540 studies, 61 were used for our systematic review. Results. There are currently a variety of both prognostic and diagnostic markers used for diagnosis and treatment of prostate cancer. The review presents the classification of markers depending on the method and medium in which they were identified. The molecular mechanisms of participation of the different genes and proteins in the pathogenesis and progression of prostate carcinoma were analyzed and the potential importance of their use in clinical practice was provided. Conclusion. Many of the existing markers can be used for screening and early detection of tumors, and they have been proved to have a prognostic value. However, contradictory findings with regard to certain proteins and genes require further study, their validation with the subsequent implementation into clinical practice.

  3. Investigation of normal tissue complication probabilities in prostate and partial breast irradiation radiotherapy techniques

    International Nuclear Information System (INIS)

    Bezak, E.; Takam, R.; Bensaleh, S.; Yeoh, E.; Marcu, L.

    2011-01-01

    Full text: Normal- Tissue-Complication Probabilities of rectum, bladder and urethra following various radiation techniques for prostate cancer were evaluated using the relative-seriality and Lyman models. NTCPs of lungs, heart and skin, their dependence on sourceposition, balloon-deformation were also investigated for HDR mammosite brachytherapy. The prostate treatment techniques included external three dimentional conformal-radiotherapy, Low-Dose-Rate brachytherapy (1-125), High-Dose-Rate brachytherapy (Ir-I92). Dose- Volume-Histograms of critical structures for prostate and breast radiotherapy, retrieved from corresponding treatment planning systems, were converted to Biological Effective Dose (BEffD)-based and Equivalent Dose(Deq)-based DVHs to account for differences in radiation delivery and fractionation schedule. Literature-based model parameters were used to calculate NTCPs. Hypofractionated 3D-CRT (2.75 Gy/fraction, total dose 55 Gy) NTCPs of rectum, bladder and urethra were less than those for standard fractionated 4-field 3D-CRT (2-Gy/fraction, 64 Gy) and dose-escalated 4- and 5-field 3D-CRT (74 Gy). Rectal and bladder NTCPs (5.2% and 6.6%) following the dose-escalated 4-field 3D-CRT (74 Gy) were the highest among analyzed techniques. The average NTCP for rectum and urethra were 0.6% and 24.7% for LDRBT and 0.5% and 11.2% for HDR-BT. For Mammosite, NTCP was estimated to be 0.1 %, 0.1 %, 1.2% and 3.5% for skin desquamation, erythema, telangiectasia and fibrosis respectively (the source positioned at the balloon centre). A 4 mm Mammosite-balloon deformation leads to overdosing of PTV regions by ∼40%, resulting in excessive skin dose and increased NTCP. Conclusions Prostate brachytherapy resulted in NTCPs lower compared to external beam techniques. Mammosite-brachytherapy resulted in no heart/lung complications regardless of balloon deformation. However, 4 mm deformation caused 0.6% increase in tissue fibrosis NTCP.

  4. The roles of prostate-specific antigen (PSA) density, prostate volume, and their zone-adjusted derivatives in predicting prostate cancer in patients with PSA less than 20.0 ng/mL.

    Science.gov (United States)

    Shen, P; Zhao, J; Sun, G; Chen, N; Zhang, X; Gui, H; Yang, Y; Liu, J; Shu, K; Wang, Z; Zeng, H

    2017-05-01

    The aim of this study was to develop nomograms for predicting prostate cancer and its zonal location using prostate-specific antigen density, prostate volume, and their zone-adjusted derivatives. A total of 928 consecutive patients with prostate-specific antigen (PSA) less than 20.0 ng/mL, who underwent transrectal ultrasound-guided transperineal 12-core prostate biopsy at West China Hospital between 2011 and 2014, were retrospectively enrolled. The patients were randomly split into training cohort (70%, n = 650) and validation cohort (30%, n = 278). Predicting models and the associated nomograms were built using the training cohort, while the validations of the models were conducted using the validation cohort. Univariate and multivariate logistic regression was performed. Then, new nomograms were generated based on multivariate regression coefficients. The discrimination power and calibration of these nomograms were validated using the area under the ROC curve (AUC) and the calibration curve. The potential clinical effects of these models were also tested using decision curve analysis. In total, 285 (30.7%) patients were diagnosed with prostate cancer. Among them, 131 (14.1%) and 269 (29.0%) had transition zone prostate cancer and peripheral zone prostate cancer. Each of zone-adjusted derivatives-based nomogram had an AUC more than 0.75. All nomograms had higher calibration and much better net benefit than the scenarios in predicting patients with or without different zones prostate cancer. Prostate-specific antigen density, prostate volume, and their zone-adjusted derivatives have important roles in detecting prostate cancer and its zonal location for patients with PSA 2.5-20.0 ng/mL. To the best of our knowledge, this is the first nomogram using these parameters to predict outcomes of 12-core prostate biopsy. These instruments can help clinicians to increase the accuracy of prostate cancer screening and to avoid unnecessary prostate biopsy. © 2017

  5. Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation

    DEFF Research Database (Denmark)

    Gusev, Alexander; Shi, Huwenbo; Kichaev, Gleb

    2016-01-01

    Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined...... with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell...... lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic...

  6. High energy transurethral thermotherapy in the treatment of benign prostatic hyperplasia: criteria to predict treatment outcome

    NARCIS (Netherlands)

    D'Ancona, F. C. H.; Francisca, E. A. E.; Hendriks, J. C. M.; Debruyne, F. M. J.; de la Rosette, J. J. M. C. H.

    1999-01-01

    In this study we analyzed the individual value of baseline parameters to predict the outcome of high energy transurethral microwave thermotherapy in the treatment of patients with lower urinary tract symptoms and benign prostatic hyperplasia. Two hundred and forty-seven patients with symptomatic

  7. Towards 3D ultrasound image based soft tissue tracking: a transrectal ultrasound prostate image alignment system.

    Science.gov (United States)

    Baumann, Michael; Mozer, Pierre; Daanen, Vincent; Troccaz, Jocelyne

    2007-01-01

    The emergence of real-time 3D ultrasound (US) makes it possible to consider image-based tracking of subcutaneous soft tissue targets for computer guided diagnosis and therapy. We propose a 3D transrectal US based tracking system for precise prostate biopsy sample localisation. The aim is to improve sample distribution, to enable targeting of unsampled regions for repeated biopsies, and to make post-interventional quality controls possible. Since the patient is not immobilized, since the prostate is mobile and due to the fact that probe movements are only constrained by the rectum during biopsy acquisition, the tracking system must be able to estimate rigid transformations that are beyond the capture range of common image similarity measures. We propose a fast and robust multi-resolution attribute-vector registration approach that combines global and local optimization methods to solve this problem. Global optimization is performed on a probe movement model that reduces the dimensionality of the search space and thus renders optimization efficient. The method was tested on 237 prostate volumes acquired from 14 different patients for 3D to 3D and 3D to orthogonal 2D slices registration. The 3D-3D version of the algorithm converged correctly in 96.7% of all cases in 6.5s with an accuracy of 1.41mm (r.m.s.) and 3.84mm (max). The 3D to slices method yielded a success rate of 88.9% in 2.3s with an accuracy of 1.37mm (r.m.s.) and 4.3mm (max).

  8. Reexamining the role of prostate specific antigen density in predicting outcome for clinically localized prostate cancer

    International Nuclear Information System (INIS)

    Ingenito, Anthony C.; Ennis, Ronald D.; Hsu, I.-C.; Begg, Melissa; Benson, Mitchell C.; Schiff, Peter B.

    1995-01-01

    Purpose/Objective To evaluate the prognostic significance of prostate specific antigen density (PSAD) in clinically localized prostate cancer treated with external beam radiation therapy and to compare with other prognostic factors. Materials and Methods Between January 1989 and December 1993, 278 patients with clinically localized prostate cancer received definitive radiotherapy using computed tomography (CT) guided conformal technique. Ninety-six patients were excluded on the basis of prior transurethral prostatectomy (n = 40), pretreatment prostate specific antigen (PSA) not evaluable (n = 46), no available treatment planning CT scan (n = 7) or lost to follow-up (n = 3). The records of 182 evaluable patients were retrospectively reviewed. Patient characteristics were as follows: T1, 39; T2, 68; T3, 75. Gleason's score 2-4, 25; 5-6, 68; 7, 40; 8-10, 35; 14 not specified. Pretreatment PSA ≤ 4, 18; 4-10, 54; 10-20, 51; 20-50, 37; > 50, 22. The median PSA was 12.6 ng/ml and median PSAD was 0.3. PSAD was defined as the ratio of the pretreatment serum PSA to the prostate volume measured from CT treatment planning scans by one investigator (A.C.I.). Prostate volumes were calculated using the prolate ellipse formula, i.e. 0.52 (H x L x W). All PSA values were determined using the Hybritech assay. Biochemical failure was defined as two consecutive elevations in PSA separated by at least 3 months and a final PSA value greater than 1 ng/ml. Biochemical disease-free survival (BDFS) was calculated using Kaplan-Meier method and differences between groups were analyzed using the logrank statistic. Multivariate analysis (Cox regression analysis) was used to compare the significance of factors identified on univariate analysis. Median follow-up was 2.1 years. Results In univariate analysis, PSA (p 4, 100%; 4-10, 78%; 10-20, 45%; 20-50, 65%; > 50, 18%. The 3 year BDFS by PSAD was 0.60, 36%. A direct multivariate analysis including PSA and PSAD was not possible due to the high

  9. Imaging of the prostate

    International Nuclear Information System (INIS)

    Turgut, A.

    2012-01-01

    technique, cancerous tissue can be differentiated from benign tissues depending on the hardness gradient and degree of elasticity loss. Nevertheless, the technique is not sufficient yet to preclude the requirement for systematic prostate biopsies. TRUS-guided prostate biopsy has been accepted as the 'gold standard' tool for the detection of prostate cancer. Currently, extended sampling protocols involving 10-12 cores with additional laterally directed cores at the aforementioned levels have been used to increase the diagnostic yield. Magnetic resonance imaging (MRI) is useful for prostate cancer detection primarily in patients with persisting suspicion for undisclosed cancer, despite having negative transrectal US and biopsy findings. MRI can also be used for the localization of cancer within the prostate and in local and distant staging of the disease. Technically, fast spin echo imaging preferably with the combination of endorectal and pelvic phased array coils is recommended for an ideal prostate MRI examination. MRI also aids in the local staging of prostate cancer, as it enables the assessment of the capsular penetration, extracapsular spread and local and distant metastasis. Accordingly, the data derived from endorectal MRI can be used with Partin nomograms to predict extracapsular spread of prostate cancer, in intermediate and high risk patients. MRI is a complementary technique to improve tumor detection by the assessment of tumor metabolism. Dynamic contrast-enhanced MRI, on the other hand, enables direct assessment of the angiogenesis associated with prostate cancer and relative peak enhancement has been accepted as the most accurate perfusion parameter for cancer detection. Diffusion- Weighted Imaging is based on the restriction of diffusion and elevation of apparent diffusion coefficient (ADC) in cancerous tissue compared to the normal prostate tissue. However, the diagnostic accuracy of the technique is diminished by the variability of the ADC values

  10. The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine.

    Directory of Open Access Journals (Sweden)

    Hayley C Whitaker

    2010-10-01

    Full Text Available Microseminoprotein-beta (MSMB regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to reduce promoter activity, suggested that the rs10993994 risk allele could result in lowered MSMB in benign tissue leading to increased prostate cancer risk.MSMB expression in benign and malignant prostate tissue was examined using immunohistochemistry and compared with the rs10993994 genotype. Urinary MSMB concentrations were determined by ELISA and correlated with urinary PSA, the presence or absence of cancer, rs10993994 genotype and age of onset. MSMB levels in prostate tissue and urine were greatly reduced with tumourigenesis. Urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades. The high risk allele was associated with heterogeneity of MSMB staining and loss of MSMB in both tissue and urine in benign prostate.These data show that some high risk alleles discovered using genome-wide association studies produce phenotypic effects with potential clinical utility. We provide the first link between a low penetrance polymorphism for prostate cancer and a potential test in human tissue and bodily fluids. There is potential to develop tissue and urinary MSMB for a biomarker of prostate cancer risk, diagnosis and disease monitoring.

  11. The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine.

    Science.gov (United States)

    Whitaker, Hayley C; Kote-Jarai, Zsofia; Ross-Adams, Helen; Warren, Anne Y; Burge, Johanna; George, Anne; Bancroft, Elizabeth; Jhavar, Sameer; Leongamornlert, Daniel; Tymrakiewicz, Malgorzata; Saunders, Edward; Page, Elizabeth; Mitra, Anita; Mitchell, Gillian; Lindeman, Geoffrey J; Evans, D Gareth; Blanco, Ignacio; Mercer, Catherine; Rubinstein, Wendy S; Clowes, Virginia; Douglas, Fiona; Hodgson, Shirley; Walker, Lisa; Donaldson, Alan; Izatt, Louise; Dorkins, Huw; Male, Alison; Tucker, Kathy; Stapleton, Alan; Lam, Jimmy; Kirk, Judy; Lilja, Hans; Easton, Douglas; Cooper, Colin; Eeles, Rosalind; Neal, David E

    2010-10-13

    Microseminoprotein-beta (MSMB) regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to reduce promoter activity, suggested that the rs10993994 risk allele could result in lowered MSMB in benign tissue leading to increased prostate cancer risk. MSMB expression in benign and malignant prostate tissue was examined using immunohistochemistry and compared with the rs10993994 genotype. Urinary MSMB concentrations were determined by ELISA and correlated with urinary PSA, the presence or absence of cancer, rs10993994 genotype and age of onset. MSMB levels in prostate tissue and urine were greatly reduced with tumourigenesis. Urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades. The high risk allele was associated with heterogeneity of MSMB staining and loss of MSMB in both tissue and urine in benign prostate. These data show that some high risk alleles discovered using genome-wide association studies produce phenotypic effects with potential clinical utility. We provide the first link between a low penetrance polymorphism for prostate cancer and a potential test in human tissue and bodily fluids. There is potential to develop tissue and urinary MSMB for a biomarker of prostate cancer risk, diagnosis and disease monitoring.

  12. Predicting tissue-specific expressions based on sequence characteristics

    KAUST Repository

    Paik, Hyojung; Ryu, Tae Woo; Heo, Hyoungsam; Seo, Seungwon; Lee, Doheon; Hur, Cheolgoo

    2011-01-01

    In multicellular organisms, including humans, understanding expression specificity at the tissue level is essential for interpreting protein function, such as tissue differentiation. We developed a prediction approach via generated sequence features from overrepresented patterns in housekeeping (HK) and tissue-specific (TS) genes to classify TS expression in humans. Using TS domains and transcriptional factor binding sites (TFBSs), sequence characteristics were used as indices of expressed tissues in a Random Forest algorithm by scoring exclusive patterns considering the biological intuition; TFBSs regulate gene expression, and the domains reflect the functional specificity of a TS gene. Our proposed approach displayed better performance than previous attempts and was validated using computational and experimental methods.

  13. Predicting tissue-specific expressions based on sequence characteristics

    KAUST Repository

    Paik, Hyojung

    2011-04-30

    In multicellular organisms, including humans, understanding expression specificity at the tissue level is essential for interpreting protein function, such as tissue differentiation. We developed a prediction approach via generated sequence features from overrepresented patterns in housekeeping (HK) and tissue-specific (TS) genes to classify TS expression in humans. Using TS domains and transcriptional factor binding sites (TFBSs), sequence characteristics were used as indices of expressed tissues in a Random Forest algorithm by scoring exclusive patterns considering the biological intuition; TFBSs regulate gene expression, and the domains reflect the functional specificity of a TS gene. Our proposed approach displayed better performance than previous attempts and was validated using computational and experimental methods.

  14. Discrimination of prostate cancer from normal peripheral zone and central gland tissue by using dynamic contrast-enhanced MR imaging

    NARCIS (Netherlands)

    Engelbrecht, Marc R.; Huisman, Henkjan J.; Laheij, Robert J. F.; Jager, Gerrit J.; van Leenders, Geert J. L. H.; Hulsbergen-van de Kaa, Christina A.; de La Rosette, Jean J. M. C. H.; Blickman, Johan G.; Barentsz, Jelle O.

    2003-01-01

    PURPOSE: To evaluate which parameters of dynamic magnetic resonance (MR) imaging and T2 relaxation rate would result in optimal discrimination of prostatic carcinoma from normal peripheral zone (PZ) and central gland (CG) tissues and to correlate these parameters with tumor stage, Gleason score,

  15. Cytogenetic support for primacy prostatic cancer in a patient presenting with a soft tissue mass in the leg

    NARCIS (Netherlands)

    Molenaar, WM; Stoepker, MEJ; deRuiter, AJ; Hoekstra, HJ; vandenBerg, E

    A 65-year-old man presented with a soft tissue mass in the leg, clinically suspect of a sarcoma. Histologic examination suggested a metastatic adenocarcinoma of the prostate, which could not be confirmed by immunohistologic studies. However, cytogenetic analysis strongly supported this diagnosis. A

  16. Prediction of Aggressive Human Prostate Cancer by Cathepsin B

    Science.gov (United States)

    2008-03-01

    Cancer Res 2004;10(12 Pt 1):4118-4124. 28. Munoz E, Gomez F, Paz JI, Casado I, Silva JM, Corcuera MT, Alonso MJ. Ki-67 immunolabeling in pre...detected prostate cancer. J Pathol 2002;197(2):148-154. 34. Claudio PP, Zamparelli A, Garcia FU, Claudio L, Ammirati G, Farina A, Bovicelli A, Russo G...JA. Distinct roles for cysteine cathepsin genes in multistage tumorigenesis. Genes Dev 2006;20(5):543-556. 47. Fernandez PL, Farre X, Nadal A

  17. Expression of P-cadherin identifies prostate-specific-antigen-negative cells in epithelial tissues of male sexual accessory organs and in prostatic carcinomas. Implications for prostate cancer biology.

    OpenAIRE

    Soler, A. P.; Harner, G. D.; Knudsen, K. A.; McBrearty, F. X.; Grujic, E.; Salazar, H.; Han, A. C.; Keshgegian, A. A.

    1997-01-01

    Cadherins constitute a family of calcium-dependent cell-cell adhesion molecules the individual members of which are essential for the sorting of cells into tissues during development. In this study, we examined the expression of E-cadherin, N-cadherin, and P-cadherin in tissues obtained from radical prostatectomies. Epithelial cells of prostatic glands, ejaculatory ducts, and seminal vesicles expressed E-cadherin but not N-cadherin. P-cadherin was expressed in epithelial cells of the seminal ...

  18. Human Papilloma Virus Detection by INNOLiPA HPV in Prostate Tissue from Men of Northeast Mexico

    Science.gov (United States)

    Rodriguez, Martha I Dávila; Morales, Cesar V Ignacio; Tovar, Anel R Aragón; Jimenez, Delia Olache; Maldonado, Edmundo Castelán; Miranda, Sandra Lara; Gutiérrez, Elva I Cortés

    2016-01-01

    Background: Prostatic adenocarcinoma by Prosate cancer (PCa) is the most prevalent cancer and the second cause of cancer-related death among men in the Western world. Human papilloma virus (HPV) may be considered as a preventable risk factor. In this study, we assessed the frequencies of HPV infection in prostatic adenocarcinoma and benign prostatic hyperplasia (BPH) cases in Northeast Mexico. Materials and Methods: A total of 87 paraffin-embedded blocks (from 25 and 62 patients with definite diagnoses of BPH and adenocarcinoma, respectively) were selected and subjected to INNOLiPA HPV Genotyping to detect 28 high- and low-risk HPV types. The rates of infection were compared in the two studied groups. Results: INNOLiPA HPV demonstrated great sensitivity for HPV detection on paraffin-embedded tissue. Global prevalence was 14.9% (13/87). HPV infection was positive in 19.4% (12/62) of patients with adenocarcinoma and 4.0% (1/25) of patients with BPH. HPV-11, which is considered to be low risk, was more prevalent. Interestingly, one patient with BPH and six with prostate cancer showed examples considered to be high risk (HPV-18, -51, -52, and -66). Conclusion: A higher rate of HPV infection among Mexican patients with prostatic carcinoma than among those with BPH was observed. HPV infections may thus contribute to the risk of prostate cancer. Further studies are required to elucidate any roles of HPV infection in prostate disease in Mexico and the effect of prevention and treatment of HPV infection on prostatic adenocarcinoma. PMID:28030912

  19. Human Papilloma Virus Detection by INNOLiPA HPV in Prostate Tissue from Men of Northeast Mexico

    Science.gov (United States)

    Dávila-Rodríguez, Martha I; Ignacio Morales, Cesar V; Aragón Tovar, Anel R; Olache Jimenez, Delia; Castelán Maldonado, Edmundo; Lara Miranda, Sandra; Cortés Gutiérrez, Elva I

    2016-11-01

    Background: Prostatic adenocarcinoma by Prosate cancer (PCa) is the most prevalent cancer and the second cause of cancer-related death among men in the Western world. Human papilloma virus (HPV) may be considered as a preventable risk factor. In this study, we assessed the frequencies of HPV infection in prostatic adenocarcinoma and benign prostatic hyperplasia (BPH) cases in Northeast Mexico. Materials and Methods: A total of 87 paraffin-embedded blocks (from 25 and 62 patients with definite diagnoses of BPH and adenocarcinoma, respectively) were selected and subjected to INNOLiPA HPV Genotyping to detect 28 high- and low-risk HPV types. The rates of infection were compared in the two studied groups. Results: INNOLiPA HPV demonstrated great sensitivity for HPV detection on paraffin-embedded tissue. Global prevalence was 14.9% (13/87). HPV infection was positive in 19.4% (12/62) of patients with adenocarcinoma and 4.0% (1/25) of patients with BPH. HPV-11, which is considered to be low risk, was more prevalent. Interestingly, one patient with BPH and six with prostate cancer showed examples considered to be high risk (HPV-18, -51, -52, and -66). Conclusion: A higher rate of HPV infection among Mexican patients with prostatic carcinoma than among those with BPH was observed. HPV infections may thus contribute to the risk of prostate cancer. Further studies are required to elucidate any roles of HPV infection in prostate disease in Mexico and the effect of prevention and treatment of HPV infection on prostatic adenocarcinoma. Creative Commons Attribution License

  20. Bone scintigraphy predicts the risk of spinal cord compression in hormone-refractory prostate cancer

    International Nuclear Information System (INIS)

    Soerdjbalie-Maikoe, Vidija; Pelger, Rob C.M.; Nijeholt, Guus A.B. Lycklama; Arndt, Jan-Willem; Zwinderman, Aeilko H.; Bril, Herman; Papapoulos, Socrates E.; Hamdy, Neveen A.T.

    2004-01-01

    In prostate cancer, confirmation of metastatic involvement of the skeleton has traditionally been achieved by bone scintigraphy, although the widespread availability of prostate-specific antigen (PSA) measurements has tended to eliminate the need for this investigation. The potential of bone scintigraphy to predict skeletal-related events, particularly spinal cord compression, after the onset of hormone refractoriness has never been investigated. The aim of this study was to establish whether a new method of evaluating bone scintigraphy would offer a better predictive value for this complication of the metastatic process than is achieved with currently available grading methods. We studied 84 patients with hormone-refractory prostate cancer who had undergone bone scintigraphy at the time of hormone escape. Tumour grading and parameters of tumour load (PSA and alkaline phosphatase activity) were available in all patients. The incidence of spinal cord compression was documented and all patients were followed up until death. Bone scintigraphy was evaluated by the conventional Soloway grading and by an additional analysis determining total or partial involvement of individual vertebrae. In contrast to the Soloway method, the new method was able to predict spinal cord compression at various spinal levels. Our data suggest that there is still a place for bone scintigraphy in the management of hormone-refractory prostate cancer. (orig.)

  1. MRI to predict prostate growth and development in children, adolescents and young adults

    International Nuclear Information System (INIS)

    Ren, Jing; Liu, Huijia; Wen, Didi; Huang, Xufang; Ren, Fang; Huan, Yi; Wang, He

    2015-01-01

    The purpose of this study was to investigate the use of MRI in predicting prostate growth and development. A total of 1,500 healthy male volunteers who underwent MRI of the pelvis were included in this prospective study. Subjects were divided into five groups according to age (group A, 2-5 years; group B, 6-10 years; group C, 11-15 years; group D, 16-20 years; group E, 21-25 years). Total prostate volume (TPV) as well as prostate central zone (CZ) and peripheral zone (PZ) were measured and evaluated on MRI. Data of the different groups were compared using variance analysis, Scheffe's method, Kruskal-Wallis H-test, and Pearson's correlation. Statistical significance was inferred at P 3 , 0.05 cm 3 , 2.83 cm 3 , 8.32 cm 3, and 11.56 cm 3 , respectively, and the median prostate development scores were 0.08, 0.69, 1.56, 2.38, and 2.74, respectively. Both TPVs and zonal anatomy scores varied significantly among the five groups (P = 0.000). TPV and zonal anatomy score increased with increasing age. MRI provides a reliable quantitative reference for prostate growth and development. (orig.)

  2. The predictive value of baseline variables in the treatment of benign prostatic hyperplasia using high-energy transurethral microwave thermotherapy

    NARCIS (Netherlands)

    D'Ancona, F. C.; Francisca, E. A.; Hendriks, J. C.; Debruyne, F. M.; de la Rosette, J. J.

    1998-01-01

    To evaluate the combination of patient age, prostate size, grade of outlet obstruction and total amount of energy, all independent predictive variables of treatment outcome in patients with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH) treated with high-energy

  3. DNA methylation signatures for prediction of biochemical recurrence after radical prostatectomy of clinically localized prostate cancer

    DEFF Research Database (Denmark)

    Haldrup, Christa; Mundbjerg, Kamilla; Vestergaard, Else Marie

    2013-01-01

    Purpose Diagnostic and prognostic tools for prostate cancer (PC) are suboptimal, causing overtreatment of indolent PC and risk of delayed treatment of aggressive PC. Here, we identify six novel candidate DNA methylation markers for PC with promising diagnostic and prognostic potential. Methods...... Microarray-based screening and bisulfite sequencing of 20 nonmalignant and 29 PC tissue specimens were used to identify new candidate DNA hypermethylation markers for PC. Diagnostic and prognostic potential was evaluated in 35 nonmalignant prostate tissue samples, 293 radical prostatectomy (RP) samples...... into low- and high-methylation subgroups, was trained in cohort 1 (HR, 1.91; 95% CI, 1.26 to 2.90) and validated in cohort 2 (HR, 2.33; 95% CI, 1.31 to 4.13). Conclusion We identified six novel candidate DNA methylation markers for PC. C1orf114 hypermethylation and a three-gene methylation signature were...

  4. Ex vivo MRI evaluation of prostate cancer: Localization and margin status prediction of prostate cancer in fresh radical prostatectomy specimens.

    Science.gov (United States)

    Heidkamp, Jan; Hoogenboom, Martijn; Kovacs, Iringo E; Veltien, Andor; Maat, Arie; Sedelaar, J P Michiel; Hulsbergen-van de Kaa, Christina A; Fütterer, Jurgen J

    2018-02-01

    To investigate the ability of high field ex vivo magnetic resonance imaging (MRI) to localize prostate cancer (PCa) and to predict the margin status in fresh radical prostatectomy (RP) specimens using histology as the reference standard. This Institutional Review Board (IRB)-approved study had written informed consent. Patients with biopsy-proved PCa and a diagnostic multiparametric 3T MRI examination of the prostate prior to undergoing RP were prospectively included. A custom-made container provided reference between the 7T ex vivo MRI obtained from fresh RP specimens and histological slicing. On ex vivo MRI, PCa was localized and the presence of positive surgical margins was determined in a double-reading session. These findings were compared with histological findings obtained from completely cut, whole-mount embedded, prostate specimens. In 12 RP specimens, histopathology revealed 36 PCa lesions, of which 17 (47%) and 20 (56%) were correlated with the ex vivo MRI in the first and second reading session, respectively. Nine of 12 (75%) index lesions were localized in the first session, in the second 10 of 12 (83%). Seven and 8 lesions of 11 lesions with Gleason score >6 and >0.5 cc were localized in the first and second session, respectively. In the first session none of the four histologically positive surgical margins (sensitivity 0%) and 9 of 13 negative margins (specificity 69%) were detected. In second session the sensitivity and specificity were 25% and 88%, respectively. Ex vivo MRI enabled accurate localization of PCa in fresh RP specimens, and the technique provided information on the margin status with high specificity. 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:439-448. © 2017 International Society for Magnetic Resonance in Medicine.

  5. Prostate health index (PHI) and prostate-specific antigen (PSA) predictive models for prostate cancer in the Chinese population and the role of digital rectal examination-estimated prostate volume.

    Science.gov (United States)

    Chiu, Peter K F; Roobol, Monique J; Teoh, Jeremy Y; Lee, Wai-Man; Yip, Siu-Ying; Hou, See-Ming; Bangma, Chris H; Ng, Chi-Fai

    2016-10-01

    To investigate PSA- and PHI (prostate health index)-based models for prediction of prostate cancer (PCa) and the feasibility of using DRE-estimated prostate volume (DRE-PV) in the models. This study included 569 Chinese men with PSA 4-10 ng/mL and non-suspicious DRE with transrectal ultrasound (TRUS) 10-core prostate biopsies performed between April 2008 and July 2015. DRE-PV was estimated using 3 pre-defined classes: 25, 40, or 60 ml. The performance of PSA-based and PHI-based predictive models including age, DRE-PV, and TRUS prostate volume (TRUS-PV) was analyzed using logistic regression and area under the receiver operating curves (AUC), in both the whole cohort and the screening age group of 55-75. PCa and high-grade PCa (HGPCa) was diagnosed in 10.9 % (62/569) and 2.8 % (16/569) men, respectively. The performance of DRE-PV-based models was similar to TRUS-PV-based models. In the age group 55-75, the AUCs for PCa of PSA alone, PSA with DRE-PV and age, PHI alone, PHI with DRE-PV and age, and PHI with TRUS-PV and age were 0.54, 0.71, 0.76, 0.78, and 0.78, respectively. The corresponding AUCs for HGPCa were higher (0.60, 0.70, 0.85, 0.83, and 0.83). At 10 and 20 % risk threshold for PCa, 38.4 and 55.4 % biopsies could be avoided in the PHI-based model, respectively. PHI had better performance over PSA-based models and could reduce unnecessary biopsies. A DRE-assessed PV can replace TRUS-assessed PV in multivariate prediction models to facilitate clinical use.

  6. Osteotomy simulation and soft tissue prediction using computer tomography scans

    International Nuclear Information System (INIS)

    Teschner, M.; Girod, S.; Girod, B.

    1999-01-01

    In this paper, a system is presented that can be used to simulate osteotomies of the skull and to estimate the resulting of tissue changes. Thus, the three-dimensional, photorealistic, postoperative appearance of a patient can be assessed. The system is based on a computer tomography scan and a photorealistic laser scan of the patient's face. In order to predict the postoperative appearance of a patient the soft tissue must follow the movement of the underlying bone. In this paper, a multi-layer soft tissue model is proposed that is based on springs. It incorporates features like skin turgor, gravity and sliding bone contact. The prediction of soft tissue changes due to bone realignments is computed using a very efficient and robust optimization method. The system can handle individual patient data sets and has been tested with several clinical cases. (author)

  7. External validation of a PCA-3-based nomogram for predicting prostate cancer and high-grade cancer on initial prostate biopsy.

    Science.gov (United States)

    Greene, Daniel J; Elshafei, Ahmed; Nyame, Yaw A; Kara, Onder; Malkoc, Ercan; Gao, Tianming; Jones, J Stephen

    2016-08-01

    The aim of this study was to externally validate a previously developed PCA3-based nomogram for the prediction of prostate cancer (PCa) and high-grade (intermediate and/or high-grade) prostate cancer (HGPCa) at the time of initial prostate biopsy. A retrospective review was performed on a cohort of 336 men from a large urban academic medical center. All men had serum PSA PCa, PSA at diagnosis, PCA3, total prostate volume (TPV), and abnormal finding on digital rectal exam (DRE). These variables were used to test the accuracy (concordance index) and calibration of a previously published PCA3 nomogram. Biopsy confirms PCa and HGPCa in 51.0% and 30.4% of validation patients, respectively. This differed from the original cohort in that it had significantly more PCa and HGPCA (51% vs. 44%, P = 0.019; and 30.4% vs. 19.1%, P PCa detection the concordance index was 75% and 77% for overall PCa and HGPCa, respectively. Calibration for overall PCa was good. This represents the first external validation of a PCA3-based prostate cancer predictive nomogram in a North American population. Prostate 76:1019-1023, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Prostate-specific antigen for pretreatment prediction and posttreatment evaluation of outcome after definitive irradiation for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kuban, Deborah A; El-Mahdi, Anas M; Schellhammer, Paul F

    1995-05-15

    Purpose: This study was undertaken to assess the predictive value of pretreatment prostate-specific antigen (PSA) and the difference between clinical and PSA disease-free status in patients with long-term follow-up after irradiation for prostatic carcinoma. Comparison of the distribution of prognostic factors between surgical and radiation series was also made. Methods and Materials: From 1975-1989, 652 patients with clinical Stage A2-C prostatic adenocarcinoma were definitively irradiated using external beam therapy. One hundred and fifty patients with banked serum and up to 14 years follow-up have pretreatment PSA levels and 355 patients with up to 17 years follow-up have posttreatment values. Treatment failure was analyzed by tumor stage, grade, and four pretreatment PSA categories. Disease-progression was evaluated by clinical and biochemical (PSA) endpoints. Prognostic factors were compared to two surgical series. Results: A significant difference was seen in clinical and PSA disease-free (PSA {<=} 4.0 ng/ml) status based on tumor grade, stage, and pretreatment PSA category. Although the expected clinical outcome has been well-documented previously, results based on posttreatment PSA levels show 5-year disease-free survivals reduced by 10-16% and 10-year survivals lessened by 15-39% depending upon the particular tumor grade and stage. The earlier stage, lower grade tumors showed the largest difference between clinical and biochemical recurrence rates at the longest interval from treatment. Even more notable were the differences in the clinical and PSA disease-free rates based on the pretreatment PSA level. Comparing the irradiated patients to two surgical series showed that the former had a larger percentage of more advanced stage tumors with more unfavorable PSA levels as compared to prostatectomy patients. Conclusion: With long-term follow-up, the pretreatment PSA level continues to be a powerful predictor of clinical and biochemical outcome in patients

  9. Relative mRNA expression of prostate-derived E-twenty-six factor and E-twenty-six variant 4 transcription factors, and of uridine phosphorylase-1 and thymidine phosphorylase enzymes, in benign and malignant prostatic tissue

    Science.gov (United States)

    CAVAZZOLA, LUCIANE ROSTIROLA; CARVALHAL, GUSTAVO FRANCO; DEVES, CANDIDA; RENCK, DAIANA; ALMEIDA, RICARDO; SANTOS, DIóGENES SANTIAGO

    2015-01-01

    Prostate cancer is the most frequent urological tumor, and the second most common cancer diagnosed in men. Incidence and mortality are variable and appear to depend on behavioral factors and genetic predisposition. The prostate-derived E-twenty-six factor (PDEF) and E-twenty-six variant 4 (ETV4) transcription factors, and the thymidine phosphorylase (TP) and uridine phosphorylase-1 (UP-1) enzymes, are reported to be components of the pathways leading to tumorigenesis and/or metastasis in a number of tumors. The present study aimed to analyze the mRNA expression levels of these proteins in prostatic cancerous and benign tissue, and their association with clinical and pathological variables. Using quantitative reverse transcription polymerase chain reaction, the mRNA expression levels of PDEF, ETV4, TP and UP-1 were studied in 52 tissue samples (31 of benign prostatic hyperplasia and 21 of prostate adenocarcinomas) obtained from patients treated by transurethral resection of the prostate or by radical prostatectomy. Relative expression was assessed using the ∆-CT method. Data was analyzed using Spearman's tests for correlation. Pbenign and malignant prostatic tissues. Further studies are necessary to define the role of these proteins as therapeutic targets in prostate cancer. PMID:26137165

  10. Near infrared spectral polarization imaging of prostate cancer tissues using Cybesin: a receptor-targeted contrast agent

    Science.gov (United States)

    Pu, Yang; Wang, W. B.; Tang, G. C.; Liang, Kexian; Achilefu, S.; Alfano, R. R.

    2013-03-01

    Cybesin, a smart contrast agent to target cancer cells, was investigated using a near infrared (NIR) spectral polarization imaging technique for prostate cancer detection. The approach relies on applying a contrast agent that can target cancer cells. Cybesin, as a small ICG-derivative dye-peptide, emit fluorescence between 750 nm and 900 nm, which is in the "tissue optical window". Cybesin was reported targeting the over-expressed bombesin receptors in cancer cells in animal model and the human prostate cancers over-expressing bombesin receptors. The NIR spectral polarization imaging study reported here demonstrated that Cybesin can be used as a smart optical biomarker and as a prostate cancer receptor targeted contrast agent.

  11. MRI to predict prostate growth and development in children, adolescents and young adults

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Jing; Liu, Huijia; Wen, Didi; Huang, Xufang; Ren, Fang; Huan, Yi [Fourth Military Medical University, Department of Radiology, Xijing Hospital, Xi' an City (China); Wang, He [Fourth Military Medical University, Department of Urology, Tangdu Hospital, Xi' an City (China)

    2014-08-06

    The purpose of this study was to investigate the use of MRI in predicting prostate growth and development. A total of 1,500 healthy male volunteers who underwent MRI of the pelvis were included in this prospective study. Subjects were divided into five groups according to age (group A, 2-5 years; group B, 6-10 years; group C, 11-15 years; group D, 16-20 years; group E, 21-25 years). Total prostate volume (TPV) as well as prostate central zone (CZ) and peripheral zone (PZ) were measured and evaluated on MRI. Data of the different groups were compared using variance analysis, Scheffe's method, Kruskal-Wallis H-test, and Pearson's correlation. Statistical significance was inferred at P < 0.05. In groups A and B, the prostates were barely visible. In group C, although TPV was measured, it was hard to distinguish CZ and PZ. In group D, 136 CZ and PZ were clearly visible. In group E, 377 CZ and PZ were clearly visible on T2-weighted imaging (T2WI). The median TPVs of groups A, B, C, D, and E were 0.00 cm{sup 3}, 0.05 cm{sup 3}, 2.83 cm{sup 3}, 8.32 cm{sup 3,} and 11.56 cm{sup 3}, respectively, and the median prostate development scores were 0.08, 0.69, 1.56, 2.38, and 2.74, respectively. Both TPVs and zonal anatomy scores varied significantly among the five groups (P = 0.000). TPV and zonal anatomy score increased with increasing age. MRI provides a reliable quantitative reference for prostate growth and development. (orig.)

  12. Isolation and genome-wide expression and methylation characterization of CD31+ cells from normal and malignant human prostate tissue

    Science.gov (United States)

    Luo, Wei; Hu, Qiang; Wang, Dan; Deeb, Kristin K.; Ma, Yingyu; Morrison, Carl D.; Liu, Song; Johnson, Candace S.; Trump, Donald L.

    2013-01-01

    Endothelial cells (ECs) are an important component involved in the angiogenesis. Little is known about the global gene expression and epigenetic regulation in tumor endothelial cells. The identification of gene expression and epigenetic difference between human prostate tumor-derived endothelial cells (TdECs) and those in normal tissues may uncover unique biological features of TdEC and facilitate the discovery of new anti-angiogenic targets. We established a method for isolation of CD31+ endothelial cells from malignant and normal prostate tissues obtained at prostatectomy. TdECs and normal-derived ECs (NdECs) showed >90% enrichment in primary culture and demonstrated microvascular endothelial cell characteristics such as cobblestone morphology in monolayer culture, diI-acetyl-LDL uptake and capillary-tube like formation in Matrigel®. In vitro primary cultures of ECs maintained expression of endothelial markers such as CD31, von Willebrand factor, intercellular adhesion molecule, vascular endothelial growth factor receptor 1, and vascular endothelial growth factor receptor 2. We then conducted a pilot study of transcriptome and methylome analysis of TdECs and matched NdECs from patients with prostate cancer. We observed a wide spectrum of differences in gene expression and methylation patterns in endothelial cells, between malignant and normal prostate tissues. Array-based expression and methylation data were validated by qRT-PCR and bisulfite DNA pyrosequencing. Further analysis of transcriptome and methylome data revealed a number of differentially expressed genes with loci whose methylation change is accompanied by an inverse change in gene expression. Our study demonstrates the feasibility of isolation of ECs from histologically normal prostate and prostate cancer via CD31+ selection. The data, although preliminary, indicates that there exist widespread differences in methylation and transcription between TdECs and NdECs. Interestingly, only a small

  13. Dosimetric factors predictive of late toxicity in prostate cancer radiotherapy; Radiotherapie prostatique: prediction de la toxicite tardive a partir des donnees dosimetriques

    Energy Technology Data Exchange (ETDEWEB)

    Crevoisier, R. de [Departement de radiotherapie, centre Eugene-Marquis, 35 - Rennes (France); Inserm, U 642, 35 - Rennes (France); Fiorino, C. [Medical Physics Department, San Raffaele Scientific Institute, Melghera, Milan (Italy); Dubray, B. [Departement de radiotherapie et de physique medicale, centre Henri-Becquerel, 76 - Rouen (France); EA 4108, UFR de medecine-pharmacie, QuantIF-LITIS, 76 - Rouen (France)

    2010-10-15

    Dose escalation in prostate cancer is made possible due to technological advances and to precise dose-volume constraints to limit normal tissue damage. This article is a literature review focusing on the correlations between exposure (doses and volumes) of organs at risk (OAR) and rectal, urinary, sexual and bone toxicity, as well as on mathematical models aiming at toxicity prediction. Dose-volume constraint recommendations are presented that have been shown to be associated with reduced rectal damage. Indeed, the clinical data is relatively strong for late rectal toxicity (bleeding), with constraints put on both the volume of the rectum receiving high doses ({>=}70 Gy) and the volume receiving intermediate doses (40 to 60 Gy). Predictive models of rectal toxicity (Normal Tissue Complication Probability) appear to accurately estimate toxicity risks. The correlations are much weaker for the bulb and the femoral heads, and nearly do not exist for the bladder. Further prospective studies are required, ideally taking into account patient-related risk factors (co-morbidities and their specific treatments), assays of normal tissue hypersensitivity to ionizing radiation and mathematical models applied on 3D images acquired under the treatment machine (e.g. Cone Beam CT). (authors)

  14. Postoperative Nomogram Predicting the 10-Year Probability of Prostate Cancer Recurrence After Radical Prostatectomy

    Science.gov (United States)

    Stephenson, Andrew J.; Scardino, Peter T.; Eastham, James A.; Bianco, Fernando J.; Dotan, Zohar A.; DiBlasio, Christopher J.; Reuther, Alwyn; Klein, Eric A.; Kattan, Michael W.

    2007-01-01

    Purpose A postoperative nomogram for prostate cancer recurrence after radical prostatectomy (RP) has been independently validated as accurate and discriminating. We have updated the nomogram by extending the predictions to 10 years after RP and have enabled the nomogram predictions to be adjusted for the disease-free interval that a patient has maintained after RP. Methods Cox regression analysis was used to model the clinical information for 1,881 patients who underwent RP for clinically-localized prostate cancer by two high-volume surgeons. The model was externally validated separately on two independent cohorts of 1,782 patients and 1,357 patients, respectively. Disease progression was defined as a rising prostate-specific antigen (PSA) level, clinical progression, radiotherapy more than 12 months postoperatively, or initiation of systemic therapy. Results The 10-year progression-free probability for the modeling set was 79% (95% CI, 75% to 82%). Significant variables in the multivariable model included PSA (P = .002), primary (P < .0001) and secondary Gleason grade (P = .0006), extracapsular extension (P < .0001), positive surgical margins (P = .028), seminal vesicle invasion (P < .0001), lymph node involvement (P = .030), treatment year (P = .008), and adjuvant radiotherapy (P = .046). The concordance index of the nomogram when applied to the independent validation sets was 0.81 and 0.79. Conclusion We have developed and validated as a robust predictive model an enhanced postoperative nomogram for prostate cancer recurrence after RP. Unique to predictive models, the nomogram predictions can be adjusted for the disease-free interval that a patient has achieved after RP. PMID:16192588

  15. Convergent RANK- and c-Met-mediated signaling components predict survival of patients with prostate cancer: an interracial comparative study.

    Science.gov (United States)

    Hu, Peizhen; Chung, Leland W K; Berel, Dror; Frierson, Henry F; Yang, Hua; Liu, Chunyan; Wang, Ruoxiang; Li, Qinlong; Rogatko, Andre; Zhau, Haiyen E

    2013-01-01

    We reported (PLoS One 6 (12):e28670, 2011) that the activation of c-Met signaling in RANKL-overexpressing bone metastatic LNCaP cell and xenograft models increased expression of RANK, RANKL, c-Met, and phosphorylated c-Met, and mediated downstream signaling. We confirmed the significance of the RANK-mediated signaling network in castration resistant clinical human prostate cancer (PC) tissues. In this report, we used a multispectral quantum dot labeling technique to label six RANK and c-Met convergent signaling pathway mediators simultaneously in formalin fixed paraffin embedded (FFPE) tissue specimens, quantify the intensity of each expression at the sub-cellular level, and investigated their potential utility as predictors of patient survival in Caucasian-American, African-American and Chinese men. We found that RANKL and neuropilin-1 (NRP-1) expression predicts survival of Caucasian-Americans with PC. A Gleason score ≥ 8 combined with nuclear p-c-Met expression predicts survival in African-American PC patients. Neuropilin-1, p-NF-κB p65 and VEGF are predictors for the overall survival of Chinese men with PC. These results collectively support interracial differences in cell signaling networks that can predict the survival of PC patients.

  16. Convergent RANK- and c-Met-mediated signaling components predict survival of patients with prostate cancer: an interracial comparative study.

    Directory of Open Access Journals (Sweden)

    Peizhen Hu

    Full Text Available We reported (PLoS One 6 (12:e28670, 2011 that the activation of c-Met signaling in RANKL-overexpressing bone metastatic LNCaP cell and xenograft models increased expression of RANK, RANKL, c-Met, and phosphorylated c-Met, and mediated downstream signaling. We confirmed the significance of the RANK-mediated signaling network in castration resistant clinical human prostate cancer (PC tissues. In this report, we used a multispectral quantum dot labeling technique to label six RANK and c-Met convergent signaling pathway mediators simultaneously in formalin fixed paraffin embedded (FFPE tissue specimens, quantify the intensity of each expression at the sub-cellular level, and investigated their potential utility as predictors of patient survival in Caucasian-American, African-American and Chinese men. We found that RANKL and neuropilin-1 (NRP-1 expression predicts survival of Caucasian-Americans with PC. A Gleason score ≥ 8 combined with nuclear p-c-Met expression predicts survival in African-American PC patients. Neuropilin-1, p-NF-κB p65 and VEGF are predictors for the overall survival of Chinese men with PC. These results collectively support interracial differences in cell signaling networks that can predict the survival of PC patients.

  17. Normal tissue complication probabilities correlated with late effects in the rectum after prostate conformal radiotherapy

    International Nuclear Information System (INIS)

    Dale, Einar; Olsen, Dag R.; Fossa, Sophie D.

    1999-01-01

    Purpose: Radiation therapy of deep-sited tumours will always result in normal tissue doses to some extent. The aim of this study was to calculate different risk estimates of late effects in the rectum for a group of cancer prostate patients treated with conformal radiation therapy (CRT) and correlate these estimates with the occurrences of late effects. Since the rectum is a hollow organ, several ways of generating dose-volume distributions over the organ are possible, and we wanted to investigate two of them. Methods and Materials: A mathematical model, known as the Lyman-Kutcher model, conventionally used to estimate normal tissue complication probabilities (NTCP) associated with radiation therapy, was applied to a material of 52 cancer prostate patients. The patients were treated with a four field box technique, with the rectum as organ at risk. Dose-volume histograms (DVH) were generated for the whole rectum (including the cavity) and of the rectum wall. One to two years after the treatment, the patients completed a questionnaire concerning bowel (rectum) related morbidity quantifying the extent of late effects. Results: A correlation analysis using Spearman's rank correlation coefficient, for NTCP values calculated from the DVHs and the patients' scores, gave correlation coefficients which were not statistically significant at the p max , of the whole rectum, correlated better to observed late toxicity than D max derived from histograms of the rectum wall. Correlation coefficients from 'high-dose' measures were larger than those calculated from the NTCP values. Accordingly, as the volume parameter of the Lyman-Kutcher model was reduced, raising the impact of small high-dose volumes on the NTCP values, the correlation between observed effects and NTCP values became significant at p < 0.01 level. Conclusions: 1) High-dose levels corresponding to small volume fractions of the cumulative dose-volume histograms were best correlated with the occurrences of late

  18. Predictive value of prostate specific antigen in a European HIV-positive cohort

    DEFF Research Database (Denmark)

    Shepherd, Leah; Borges, Álvaro H; Ravn, Lene

    2016-01-01

    BACKGROUND: It is common practice to use prostate specific antigen (PSA) ≥4.0 ng/ml as a clinical indicator for men at risk of prostate cancer (PCa), however, this is unverified in HIV+ men. We aimed to describe kinetics and predictive value of PSA for PCa in HIV+ men. METHODS: A nested case...... control study of 21 men with PCa and 40 matched-controls within EuroSIDA was conducted. Prospectively stored plasma samples before PCa (or matched date in controls) were measured for the following markers: total PSA (tPSA), free PSA (fPSA), testosterone and sex hormone binding globulin (SHBG). Conditional...... logistic regression models investigated associations between markers and PCa. Mixed models were used to describe kinetics. Sensitivity and specificity of using tPSA >4 ng/ml to predict PCa was calculated. Receiver operating characteristic curves were used to identify optimal cutoffs in HIV+ men for total...

  19. Comparison of normal tissue pharmacokinetics with 111In/9Y monoclonal antibody m170 for breast and prostate cancer

    International Nuclear Information System (INIS)

    Lehmann, Joerg; DeNardo, Gerald L.; Yuan, Aina; Shen Sui; O'Donnell, Robert T.; Richman, Carol M.; De Nardo, Sally J.

    2006-01-01

    Purpose: Radioactivity deposition in normal tissues limits the dose deliverable by radiopharmaceuticals (RP) in radioimmunotherapy (RIT). This study investigated the absorbed radiation dose in normal tissues for prostate cancer patients in comparison to breast cancer patients for 2 RPs using the monoclonal antibody (MAb) m170. Methods and Materials: 111 In-DOTA-glycylglycylglycyl-L-p-isothiocyanatophenylalanine amide (GGGF)-m170 and 111 In-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) 2-iminothiolane (2IT)-m170, representing the same MAb and chelate with and without a cleavable linkage, were studied in 13 breast cancer and 26 prostate cancer patients. Dosimetry for 9 Y was calculated using 111 In MAb pharmacokinetics from the initial imaging study for each patient, using reference man- and patient-specific masses. Results: The reference man-specific radiation doses (cGy/MBq) were not significantly different for the breast and the prostate cancer patients for both RPs in all but one tissue-RP combination (liver, DOTA-2IT). The patient-specific doses had differences between the groups most of which can be related to weight differences. Conclusions: Similar normal tissue doses were calculated for two groups of patients having different cancers and genders. This similarity combined with continued careful analysis of the imaging data might allow the use of higher starting doses in early phase RIT studies

  20. Proteins Annexin A2 and PSA in Prostate Cancer Biopsies Do Not Predict Biochemical Failure.

    Science.gov (United States)

    Lamb, David S; Sondhauss, Sven; Dunne, Jonathan C; Woods, Lisa; Delahunt, Brett; Ferguson, Peter; Murray, Judith; Nacey, John N; Denham, James W; Jordan, T William

    2017-12-01

    We previously reported the use of mass spectrometry and western blotting to identify proteins from tumour regions of formalin-fixed paraffin-embedded biopsies from 16 men who presented with apparently localized prostate cancer, and found that annexin A2 (ANXA2) appeared to be a better predictor of subsequent biochemical failure than prostate-specific antigen (PSA). In this follow-up study, ANXA2 and PSA were measured using western blotting of proteins extracted from biopsies from 37 men from a subsequent prostate cancer trial. No significant differences in ANXA2 and PSA levels were observed between men with and without biochemical failure. The statistical effect sizes were small, d=0.116 for ANXA2, and 0.266 for PSA. ANXA2 and PSA proteins measured from biopsy tumour regions are unlikely to be good biomarkers for prediction of the clinical outcome of prostate cancer presenting with apparently localized disease. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. Peripheral lymphocyte subset variation predicts prostate cancer carbon ion radiotherapy outcomes

    Science.gov (United States)

    Shi, Ze-Liang; Li, Bing-Xin; Wu, Xian-Wei; Li, Ping; Zhang, Qing; Wei, Xun-Bin; Fu, Shen

    2016-01-01

    The immune system plays a complementary role in the cytotoxic activity of radiotherapy. Here, we examined changes in immune cell subsets after heavy ion therapy for prostate cancer. The lymphocyte counts were compared with acute radiotherapy-related toxicity, defined according to the Common Terminology Criteria for Adverse Events, and short-term local efficacy, defined based on prostate-specific antigen concentrations. Confirmed prostate cancer patients who had not received previous radiotherapy were administered carbon ion radiotherapy (CIR) in daily fractions of 2.74 GyE with a total dose of 63-66 GyE. Lymphocyte subset counts were investigated before, during and after radiotherapy, and at a 1 month follow-up. Most notable among our findings, the CD4/CD8 ratio and CD19+ cell counts were consistently higher in patients with a complete response (CR) or partial response (PR) to CIR than in those classified in the stable disease (SD) group (P<0.05 for both). But CD3+ and CD8+ cell counts were lower in the CR and PR groups than in the SD group. These results indicate that variations in peripheral lymphocyte subpopulations are predictive of outcome after CIR for prostate cancer. PMID:27029063

  2. Proton MR spectroscopy of the prostate

    Energy Technology Data Exchange (ETDEWEB)

    Mueller-Lisse, Ullrich G. [Dept. of Clinical Radiology, Klinikum der Universitaet Muenchen, Standorte Grosshadern und Innenstadt, Ziemssenstrasse 1, D-80336 Munich (Germany)], E-mail: ullrich.mueller-lisse@med.uni-muenchen.de; Scherr, Michael K. [Dept. of Clinical Radiology, Klinikum der Universitaet Muenchen, Standorte Grosshadern und Innenstadt, Ziemssenstrasse 1, D-80336 Munich (Germany)

    2007-09-15

    Purpose: To summarize current technical and biochemical aspects and clinical applications of proton magnetic resonance spectroscopy (MRS) of the human prostate in vivo. Material and methods: Pertinent radiological and biochemical literature was searched and retrieved via electronic media (medline, pubmed). Basic concepts of MRS of the prostate and its clinical applications were extracted. Results: Clinical MRS is usually based on point resolved spectroscopy (PRESS) or spin echo (SE) sequences, along with outer volume suppression of signals from outside of the prostate. MRS of the prostate detects indicator lines of citrate, choline, and creatine. While healthy prostate tissue demonstrates high levels of citrate and low levels of choline that marks cell wall turnover, prostate cancer utilizes citrate for energy metabolism and shows high levels of choline. The ratio of (choline + creatine)/citrate distinguishes between healthy tissue and prostate cancer. Particularly when combined with magnetic resonance (MR) imaging, three-dimensional MRS imaging (3D-CSI, or 3D-MRSI) detects and localizes prostate cancer in the entire prostate with high sensitivity and specificity. Combined MR imaging and 3D-MRSI exceed the sensitivity and specificity of sextant biopsy of the prostate. When MRS and MR imaging agree on prostate cancer presence, the positive predictive value is about 80-90%. Distinction between healthy tissue and prostate cancer principally is maintained after various therapeutic treatments, including hormone ablation therapy, radiation therapy, and cryotherapy of the prostate. Conclusions: Since it is non-invasive, reliable, radiation-free, and essentially repeatable, combined MR imaging and 3D-MRSI of the prostate lends itself to the planning of biopsy and therapy, and to post-therapeutic follow-up. For broad clinical acceptance, it will be necessary to facilitate MRS examinations and their evaluation and make MRS available to a wider range of institutions.

  3. Prostate cancer risk prediction based on complete prostate cancer family history.

    Science.gov (United States)

    Albright, Frederick; Stephenson, Robert A; Agarwal, Neeraj; Teerlink, Craig C; Lowrance, William T; Farnham, James M; Albright, Lisa A Cannon

    2015-03-01

    Prostate cancer (PC) relative risks (RRs) are typically estimated based on status of close relatives or presence of any affected relatives. This study provides RR estimates using extensive and specific PC family history. A retrospective population-based study was undertaken to estimate RRs for PC based on complete family history of PC. A total of 635,443 males, all with ancestral genealogy data, were analyzed. RRs for PC were determined based upon PC rates estimated from males with no PC family history (without PC in first, second, or third degree relatives). RRs were determined for a variety of constellations, for example, number of first through third degree relatives; named (grandfather, father, uncle, cousins, brothers); maternal, paternal relationships, and age of onset. In the 635,443 males analyzed, 18,105 had PC. First-degree RRs ranged from 2.46 (=1 first-degree relative affected, CI = 2.39-2.53) to 7.65 (=4 first-degree relatives affected, CI = 6.28-9.23). Second-degree RRs for probands with 0 affected first-degree relatives ranged from 1.51 (≥1 second-degree relative affected, CI = 1.47-1.56) to 3.09 (≥5 second-degree relatives affected, CI = 2.32-4.03). Third-degree RRs with 0 affected first- and 0 affected second-degree relatives ranged from 1.15 (≥1 affected third-degree relative, CI = 1.12-1.19) to 1.50 (≥5 affected third-degree relatives, CI = 1.35-1.66). RRs based on age at diagnosis were higher for earlier age at diagnoses; for example, RR = 5.54 for ≥1 first-degree relative diagnosed before age 50 years (CI = 1.12-1.19) and RR = 1.78 for >1 second-degree relative diagnosed before age 50 years, CI = 1.33, 2.33. RRs for equivalent maternal versus paternal family history were not significantly different. A more complete PC family history using close and distant relatives and age at diagnosis results in a wider range of estimates of individual RR that are potentially more accurate than RRs estimated

  4. Tissue Microarray Assessment of Novel Prostate Cancer Biomarkers AMACR and EZH2 and Immunologic Response to Them in African-American and Caucasian Men

    National Research Council Canada - National Science Library

    Mehra, Rohit

    2007-01-01

    .... We constructed 5 tissue microarrays representing 40 African-American and 159 Caucasian prostate cancer patients and performed immunohistochemistry on these arrays using antibody to AMACR and EZH2...

  5. Tissue Microarray Assessment of Novel Prostate Cancer Biomarkers AMACR and EZH2 and Immunologic Response to them in African-American and Caucasian Men

    National Research Council Canada - National Science Library

    Mehra, Rohit

    2006-01-01

    .... We constructed 5 tissue microarrays representing 40 African-American and 159 Caucasian prostate cancer patients and performed immunohistochemistry on these arrays using antibodies to AMACR and EZH2...

  6. Asymptomatic prostatic inflammation in men with clinical BPH and erectile dysfunction affects the positive predictive value of prostate-specific antigen.

    Science.gov (United States)

    Agnihotri, Shalini; Mittal, Rama Devi; Kapoor, Rakesh; Mandhani, Anil

    2014-10-01

    To test the hypothesis that sexual dysfunction in elderly men with benign prostatic hyperplasia leads to prostatic inflammation, diagnosed by prostatic fluid interleukin-8 (IL-8), which lowers the positive predictive value of prostate-specific antigen (PSA). Overall, 160 men with lower urinary tract symptoms between 50 and 75 years of age with an elevated PSA level of more than 4 ng/ml with normal digital rectal examination and 50 age-matched controls with normal PSA level were prospectively evaluated for prostatic fluid IL-8 levels. Erectile dysfunction was measured by self-administered questionnaire of the Sexual Health Inventory for Men. Total and free serum PSA levels and IL-8 in prostatic fluid were measured 6 to 8 weeks after a course of 400mg of ofloxacin and 20mg of piroxicam given daily for 2 weeks. Transrectal ultrasonography-guided biopsy was done only when PSA level did not decrease less than 4 ng/ml. Mean ages of patients and controls were 63.18 (standard deviation [SD]±7.10) and 60.18 (SD+6.02) years, respectively. Mean concentration of IL-8 in prostatic fluid of the patients was significantly higher, i.e., 6678 pg/ml (SD±1985.7) than in control, i.e., 1543 pg/ml (SD±375.7) (Pprostatic hyperplasia and erectile dysfunction had significant inflammation of the prostate to cause spurious rise in PSA level resulting in an unnecessary biopsy. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Risk score predicts high-grade prostate cancer in DNA-methylation positive, histopathologically negative biopsies.

    Science.gov (United States)

    Van Neste, Leander; Partin, Alan W; Stewart, Grant D; Epstein, Jonathan I; Harrison, David J; Van Criekinge, Wim

    2016-09-01

    Prostate cancer (PCa) diagnosis is challenging because efforts for effective, timely treatment of men with significant cancer typically result in over-diagnosis and repeat biopsies. The presence or absence of epigenetic aberrations, more specifically DNA-methylation of GSTP1, RASSF1, and APC in histopathologically negative prostate core biopsies has resulted in an increased negative predictive value (NPV) of ∼90% and thus could lead to a reduction of unnecessary repeat biopsies. Here, it is investigated whether, in methylation-positive men, DNA-methylation intensities could help to identify those men harboring high-grade (Gleason score ≥7) PCa, resulting in an improved positive predictive value. Two cohorts, consisting of men with histopathologically negative index biopsies, followed by a positive or negative repeat biopsy, were combined. EpiScore, a methylation intensity algorithm was developed in methylation-positive men, using area under the curve of the receiver operating characteristic as metric for performance. Next, a risk score was developed combining EpiScore with traditional clinical risk factors to further improve the identification of high-grade (Gleason Score ≥7) cancer. Compared to other risk factors, detection of DNA-methylation in histopathologically negative biopsies was the most significant and important predictor of high-grade cancer, resulting in a NPV of 96%. In methylation-positive men, EpiScore was significantly higher for those with high-grade cancer detected upon repeat biopsy, compared to those with either no or low-grade cancer. The risk score resulted in further improvement of patient risk stratification and was a significantly better predictor compared to currently used metrics as PSA and the prostate cancer prevention trial (PCPT) risk calculator (RC). A decision curve analysis indicated strong clinical utility for the risk score as decision-making tool for repeat biopsy. Low DNA-methylation levels in PCa-negative biopsies led

  8. National Economic Conditions and Patient Insurance Status Predict Prostate Cancer Diagnosis Rates and Management Decisions.

    Science.gov (United States)

    Weiner, Adam B; Conti, Rena M; Eggener, Scott E

    2016-05-01

    The recent Great Recession from December 2007 to June 2009 presents a unique opportunity to examine whether the incidence of nonpalpable prostate cancer decreases while conservative management for nonpalpable prostate cancer increases during periods of national economic hardship. We derived rates of national monthly diagnosis and conservative management for screen detected, nonpalpable prostate cancer and patient level insurance status from the SEER (Surveillance, Epidemiology and End Results) database from 2004 to 2011. We derived monthly statistics on national unemployment rates, inflation, median household income and S&P 500® closing values from government sources. Using linear and logistic multivariable regression we measured the correlation of national macroeconomic conditions with prostate cancer diagnosis and treatment patterns. We evaluated patient level predictors of conservative management to determine whether being insured by Medicaid or uninsured increased the use of conservative management. Diagnosis rates correlated positively with the S&P 500 monthly close (coefficient 24.90, 95% CI 6.29-43.50, p = 0.009). Conservative management correlated negatively with median household income (coefficient -49.13, 95% CI -69.29--28.98, p management compared to that in men with private insurance. As indicated by a significant interaction term being diagnosed during the Great Recession increased the Medicaid insurance predictive value of conservative management (OR 1.30, 95% CI 1.02-1.68, p = 0.037). National economic hardship was associated with decreased diagnosis rates of nonpalpable prostate cancer and increased conservative management. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  9. Predicting Tissue-Specific Enhancers in the Human Genome

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Loots, Gabriela G.; Nobrega, Marcelo A.; Ovcharenko, Ivan

    2006-07-01

    Determining how transcriptional regulatory signals areencoded in vertebrate genomes is essential for understanding the originsof multi-cellular complexity; yet the genetic code of vertebrate generegulation remains poorly understood. In an attempt to elucidate thiscode, we synergistically combined genome-wide gene expression profiling,vertebrate genome comparisons, and transcription factor binding siteanalysis to define sequence signatures characteristic of candidatetissue-specific enhancers in the human genome. We applied this strategyto microarray-based gene expression profiles from 79 human tissues andidentified 7,187 candidate enhancers that defined their flanking geneexpression, the majority of which were located outside of knownpromoters. We cross-validated this method for its ability to de novopredict tissue-specific gene expression and confirmed its reliability in57 of the 79 available human tissues, with an average precision inenhancer recognition ranging from 32 percent to 63 percent, and asensitivity of 47 percent. We used the sequence signatures identified bythis approach to assign tissue-specific predictions to ~;328,000human-mouse conserved noncoding elements in the human genome. Byoverlapping these genome-wide predictions with a large in vivo dataset ofenhancers validated in transgenic mice, we confirmed our results with a28 percent sensitivity and 50 percent precision. These results indicatethe power of combining complementary genomic datasets as an initialcomputational foray into the global view of tissue-specific generegulation in vertebrates.

  10. Secondary Circulating Prostate Cells Predict Biochemical Failure in Prostate Cancer Patients after Radical Prostatectomy and without Evidence of Disease

    Directory of Open Access Journals (Sweden)

    Nigel P. Murray

    2013-01-01

    Full Text Available Introduction. Although 90% of prostate cancer is considered to be localized, 20%–30% of patients will experience biochemical failure (BF, defined as serum PSA >0.2 ng/mL, after radical prostatectomy (RP. The presence of circulating prostate cells (CPCs in men without evidence of BF may be useful to predict patients at risk for BF. We describe the frequency of CPCs detected after RP, relation with clinicopathological parameters, and association with biochemical failure. Methods and Patients. Serial blood samples were taken during followup after RP, mononuclear cells were obtained by differential gel centrifugation, and CPCs identified using standard immunocytochemistry using anti-PSA monoclonal antibodies. Age, pathological stage (organ confined, nonorgan confined, pathological grade, margin status (positive, negative, extracapsular extension, perineural, vascular, and lymphatic infiltration (positive, negative were compared with the presence/absence of CPCs and with and without biochemical failure. Kaplan Meier methods were used to compare the unadjusted biochemical failure free survival of patients with and without CPCs. Results. 114 men participated, and secondary CPCs were detected more frequently in patients with positive margins, extracapsular extension, and vascular and lymphatic infiltration and were associated with biochemical failure independent of these clinicopathological variables, and with a shorter time to BF. Conclusions. Secondary CPCs are an independent risk factor associated with increased BF in men with a PSA <0.2 ng/mL after radical prostatectomy, but do not determine if the recurrence is due to local or systemic disease. These results warrant larger studies to confirm the findings.

  11. First off-time treatment prostate-specific antigen kinetics predicts survival in intermittent androgen deprivation for prostate cancer.

    Science.gov (United States)

    Sanchez-Salas, Rafael; Olivier, Fabien; Prapotnich, Dominique; Dancausa, José; Fhima, Mehdi; David, Stéphane; Secin, Fernando P; Ingels, Alexandre; Barret, Eric; Galiano, Marc; Rozet, François; Cathelineau, Xavier

    2016-01-01

    Prostate-specific antigen (PSA) doubling time is relying on an exponential kinetic pattern. This pattern has never been validated in the setting of intermittent androgen deprivation (IAD). Objective is to analyze the prognostic significance for PCa of recurrent patterns in PSA kinetics in patients undergoing IAD. A retrospective study was conducted on 377 patients treated with IAD. On-treatment period (ONTP) consisted of gonadotropin-releasing hormone agonist injections combined with oral androgen receptor antagonist. Off-treatment period (OFTP) began when PSA was lower than 4 ng/ml. ONTP resumed when PSA was higher than 20 ng/ml. PSA values of each OFTP were fitted with three basic patterns: exponential (PSA(t) = λ.e(αt)), linear (PSA(t) = a.t), and power law (PSA(t) = a.t(c)). Univariate and multivariate Cox regression model analyzed predictive factors for oncologic outcomes. Only 45% of the analyzed OFTPs were exponential. Linear and power law PSA kinetics represented 7.5% and 7.7%, respectively. Remaining fraction of analyzed OFTPs (40%) exhibited complex kinetics. Exponential PSA kinetics during the first OFTP was significantly associated with worse oncologic outcome. The estimated 10-year cancer-specific survival (CSS) was 46% for exponential versus 80% for nonexponential PSA kinetics patterns. The corresponding 10-year probability of castration-resistant prostate cancer (CRPC) was 69% and 31% for the two patterns, respectively. Limitations include retrospective design and mixed indications for IAD. PSA kinetic fitted with exponential pattern in approximately half of the OFTPs. First OFTP exponential PSA kinetic was associated with a shorter time to CRPC and worse CSS. © 2015 Wiley Periodicals, Inc.

  12. A High-Fat Diet Containing Lard Accelerates Prostate Cancer Progression and Reduces Survival Rate in Mice: Possible Contribution of Adipose Tissue-Derived Cytokines

    Directory of Open Access Journals (Sweden)

    Han Jin Cho

    2015-04-01

    Full Text Available To examine the effects of high-fat diet (HFD containing lard on prostate cancer development and progression and its underlying mechanisms, transgenic adenocarcinoma mouse prostate (TRAMP and TRAMP-C2 allograft models, as well as in vitro culture models, were employed. In TRAMP mice, HFD feeding increased the incidence of poorly differentiated carcinoma and decreased that of prostatic intraepithelial neoplasia in the dorsolateral lobes of the prostate, which was accompanied by increased expression of proteins associated with proliferation and angiogenesis. HFD feeding also led to increased metastasis and decreased survival rate in TRAMP mice. In the allograft model, HFD increased solid tumor growth, the expression of proteins related to proliferation/angiogenesis, the number of lipid vacuoles in tumor tissues, and levels of several cytokines in serum and adipose tissue. In vitro results revealed that adipose tissue-conditioned media from HFD-fed mice stimulated the proliferation and migration of prostate cancer cells and angiogenesis compared to those from control-diet-fed mice. These results indicate that the increase of adipose tissue-derived soluble factors by HFD feeding plays a role in the growth and metastasis of prostate cancer via endocrine and paracrine mechanisms. These results provide evidence that a HFD containing lard increases prostate cancer development and progression, thereby reducing the survival rate.

  13. Combination of prostate imaging reporting and data system (PI-RADS) score and prostate-specific antigen (PSA) density predicts biopsy outcome in prostate biopsy naïve patients.

    Science.gov (United States)

    Washino, Satoshi; Okochi, Tomohisa; Saito, Kimitoshi; Konishi, Tsuzumi; Hirai, Masaru; Kobayashi, Yutaka; Miyagawa, Tomoaki

    2017-02-01

    To assess the value of the Prostate Imaging Reporting and Data System (PI-RADS) scoring system, for prostate multi-parametric magnetic resonance imaging (mpMRI) to detect prostate cancer, and classical parameters, such as prostate-specific antigen (PSA) level, prostate volume and PSA density, for predicting biopsy outcome in biopsy naïve patients who have suspected prostate cancer. Patients who underwent mpMRI at our hospital, and who had their first prostate biopsy between July 2010 and April 2014, were analysed retrospectively. The prostate biopsies were taken transperineally under transrectal ultrasonography guidance. In all, 14 cores were biopsied as a systematic biopsy in all patients. Two cognitive fusion-targeted biopsy cores were added for each lesion in patients who had suspicious or equivocal lesions on mpMRI. The PI-RADS scoring system version 2.0 (PI-RADS v2) was used to describe the MRI findings. Univariate and multivariate analyses were performed to determine significant predictors of prostate cancer and clinically significant prostate cancer. In all, 288 patients were analysed. The median patient age, PSA level, prostate volume and PSA density were 69 years, 7.5 ng/mL, 28.7 mL, and 0.26 ng/mL/mL, respectively. The biopsy results were benign, clinically insignificant, and clinically significant prostate cancer in 129 (45%), 18 (6%) and 141 (49%) patients, respectively. The multivariate analysis revealed that PI-RADS v2 score and PSA density were independent predictors for prostate cancer and clinically significant prostate cancer. When PI-RADS v2 score and PSA density were combined, a PI-RADS v2 score of ≥4 and PSA density ≥0.15 ng/mL/mL, or PI-RADS v2 score of 3 and PSA density of ≥0.30 ng/mL/mL, was associated with the highest clinically significant prostate cancer detection rates (76-97%) on the first biopsy. Of the patients in this group with negative biopsy results, 22% were subsequently diagnosed as prostate cancer. In contrast, a PI

  14. Expression changes in the stroma of prostate cancer predict subsequent relapse.

    Directory of Open Access Journals (Sweden)

    Zhenyu Jia

    Full Text Available Biomarkers are needed to address overtreatment that occurs for the majority of prostate cancer patients that would not die of the disease but receive radical treatment. A possible barrier to biomarker discovery may be the polyclonal/multifocal nature of prostate tumors as well as cell-type heterogeneity between patient samples. Tumor-adjacent stroma (tumor microenvironment is less affected by genetic alteration and might therefore yield more consistent biomarkers in response to tumor aggressiveness. To this end we compared Affymetrix gene expression profiles in stroma near tumor and identified a set of 115 probe sets for which the expression levels were significantly correlated with time-to-relapse. We also compared patients that chemically relapsed shortly after prostatectomy (<1 year, and patients that did not relapse in the first four years after prostatectomy. We identified 131 differentially expressed microarray probe sets between these two categories. 19 probe sets (15 genes overlapped between the two gene lists with p<0.0001. We developed a PAM-based classifier by training on samples containing stroma near tumor: 9 rapid relapse patient samples and 9 indolent patient samples. We then tested the classifier on 47 different samples, containing 90% or more stroma. The classifier predicted the risk status of patients with an average accuracy of 87%. This is the first general tumor microenvironment-based prognostic classifier. These results indicate that the prostate cancer microenvironment exhibits reproducible changes useful for predicting outcomes for patients.

  15. Multivariate normal tissue complication probability modeling of gastrointestinal toxicity after external beam radiotherapy for localized prostate cancer

    International Nuclear Information System (INIS)

    Cella, Laura; D’Avino, Vittoria; Liuzzi, Raffaele; Conson, Manuel; Doria, Francesca; Faiella, Adriana; Loffredo, Filomena; Salvatore, Marco; Pacelli, Roberto

    2013-01-01

    The risk of radio-induced gastrointestinal (GI) complications is affected by several factors other than the dose to the rectum such as patient characteristics, hormonal or antihypertensive therapy, and acute rectal toxicity. Purpose of this work is to study clinical and dosimetric parameters impacting on late GI toxicity after prostate external beam radiotherapy (RT) and to establish multivariate normal tissue complication probability (NTCP) model for radiation-induced GI complications. A total of 57 men who had undergone definitive RT for prostate cancer were evaluated for GI events classified using the RTOG/EORTC scoring system. Their median age was 73 years (range 53–85). The patients were assessed for GI toxicity before, during, and periodically after RT completion. Several clinical variables along with rectum dose-volume parameters (Vx) were collected and their correlation to GI toxicity was analyzed by Spearman’s rank correlation coefficient (Rs). Multivariate logistic regression method using resampling techniques was applied to select model order and parameters for NTCP modeling. Model performance was evaluated through the area under the receiver operating characteristic curve (AUC). At a median follow-up of 30 months, 37% (21/57) patients developed G1-2 acute GI events while 33% (19/57) were diagnosed with G1-2 late GI events. An NTCP model for late mild/moderate GI toxicity based on three variables including V65 (OR = 1.03), antihypertensive and/or anticoagulant (AH/AC) drugs (OR = 0.24), and acute GI toxicity (OR = 4.3) was selected as the most predictive model (Rs = 0.47, p < 0.001; AUC = 0.79). This three-variable model outperforms the logistic model based on V65 only (Rs = 0.28, p < 0.001; AUC = 0.69). We propose a logistic NTCP model for late GI toxicity considering not only rectal irradiation dose but also clinical patient-specific factors. Accordingly, the risk of G1-2 late GI increases as V65 increases, it is higher for patients experiencing

  16. Evaluation of an Automated Analysis Tool for Prostate Cancer Prediction Using Multiparametric Magnetic Resonance Imaging.

    Directory of Open Access Journals (Sweden)

    Matthias C Roethke

    Full Text Available To evaluate the diagnostic performance of an automated analysis tool for the assessment of prostate cancer based on multiparametric magnetic resonance imaging (mpMRI of the prostate.A fully automated analysis tool was used for a retrospective analysis of mpMRI sets (T2-weighted, T1-weighted dynamic contrast-enhanced, and diffusion-weighted sequences. The software provided a malignancy prediction value for each image pixel, defined as Malignancy Attention Index (MAI that can be depicted as a colour map overlay on the original images. The malignancy maps were compared to histopathology derived from a combination of MRI-targeted and systematic transperineal MRI/TRUS-fusion biopsies.In total, mpMRI data of 45 patients were evaluated. With a sensitivity of 85.7% (with 95% CI of 65.4-95.0, a specificity of 87.5% (with 95% CI of 69.0-95.7 and a diagnostic accuracy of 86.7% (with 95% CI of 73.8-93.8 for detection of prostate cancer, the automated analysis results corresponded well with the reported diagnostic accuracies by human readers based on the PI-RADS system in the current literature.The study revealed comparable diagnostic accuracies for the detection of prostate cancer of a user-independent MAI-based automated analysis tool and PI-RADS-scoring-based human reader analysis of mpMRI. Thus, the analysis tool could serve as a detection support system for less experienced readers. The results of the study also suggest the potential of MAI-based analysis for advanced lesion assessments, such as cancer extent and staging prediction.

  17. Quantitative PET Imaging with Novel HER3 Targeted Peptides Selected by Phage Display to Predict Androgen Independent Prostate Cancer Progression

    Science.gov (United States)

    2017-08-01

    Independent Prostate Cancer Progression PRINCIPAL INVESTIGATOR: Benjamin Larimer, PhD CONTRACTING ORGANIZATION: Massachusetts General Hospital Boston...3. DATES COVERED 1 Aug 2016 – 31 July 2017 4. TITLE AND SUBTITLE Cancer Progression 5a. CONTRACT NUMBER Quantitative PET Imaging with Novel HER3...Targeted Peptides Selected by Phage Display to Predict Androgen-Independent Prostate Cancer Progression 5b. GRANT NUMBER W81XWH-16-1-0447 5c

  18. Infiltration of tumour-associated macrophages in prostate biopsy specimens is predictive of disease progression after hormonal therapy for prostate cancer.

    Science.gov (United States)

    Nonomura, Norio; Takayama, Hitoshi; Nakayama, Masashi; Nakai, Yasutomo; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Aozasa, Katsuyuki; Tsujimura, Akira

    2011-06-01

    • To evaluate tumour-associated macrophage (TAM) infiltration in prostate biopsy specimens as a possible prognostic factor for prostate cancer (PCa) after hormonal therapy. • Immunostaining of TAMs in prostate biopsy specimens was performed using a monoclonal antibody CD68 for 71 patients having PCa treated with hormonal therapy. • Six microscopic (×400) fields around the cancer foci were selected for TAM counting. • The median value of serum prostate-specific antigen (PSA) was 50.1 ng/mL, and the median TAM count was 22. • Recurrence-free survival was significantly better in patients with fewer TAMs (<22) than in those with higher numbers of TAMs (≥22) (P < 0.001). • TAM count was higher in those with higher serum PSA (PSA), higher Gleason score, clinical T stage or those with PSA failure. Cox multivariate analysis showed that TAM count is one of the prognostic factors for PCa treated by hormonal therapy (P < 0.0001). • TAM infiltration in prostate needle biopsy specimens is a useful predictive factor for PSA failure or progression of PCa after hormonal therapy. © 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.

  19. Prediction of the cumulated dose for external beam irradiation of prostate cancer patients with 3D-CRT technique

    Directory of Open Access Journals (Sweden)

    Giżyńska Marta

    2016-03-01

    Full Text Available Nowadays in radiotherapy, much effort is taken to minimize the irradiated volume and consequently minimize doses to healthy tissues. In our work, we tested the hypothesis that the mean dose distribution calculated from a few first fractions can serve as prediction of the cumulated dose distribution, representing the whole treatment. We made our tests for 25 prostate cancer patients treated with three orthogonal fields technique. We did a comparison of dose distribution calculated as a sum of dose distribution from each fraction with a dose distribution calculated with isocenter shifted for a mean setup error from a few first fractions. The cumulative dose distribution and predicted dose distributions are similar in terms of gamma (3 mm 3% analysis, under condition that we know setup error from seven first fractions. We showed that the dose distribution calculated for the original plan with the isocenter shifted to the point, defined as the original isocenter corrected of the mean setup error estimated from the first seven fractions supports our hypothesis, i.e. can serve as a prediction for cumulative dose distribution.

  20. A four-kallikrein panel for the prediction of repeat prostate biopsy: data from the European Randomized Study of Prostate Cancer screening in Rotterdam, Netherlands.

    Science.gov (United States)

    Gupta, A; Roobol, M J; Savage, C J; Peltola, M; Pettersson, K; Scardino, P T; Vickers, A J; Schröder, F H; Lilja, H

    2010-08-24

    Most men with elevated levels of prostate-specific antigen (PSA) do not have prostate cancer, leading to a large number of unnecessary biopsies. A statistical model based on a panel of four kallikreins has been shown to predict the outcome of a first prostate biopsy. In this study, we apply the model to an independent data set of men with previous negative biopsy but persistently elevated PSA. The study cohort consisted of 925 men with a previous negative prostate biopsy and elevated PSA (>or=3 ng ml(-1)), with 110 prostate cancers detected (12%). A previously published statistical model was applied, with recalibration to reflect the lower positive biopsy rates on rebiopsy. The full-kallikrein panel had higher discriminative accuracy than PSA and DRE alone, with area under the curve (AUC) improving from 0.58 (95% confidence interval (CI): 0.52, 0.64) to 0.68 (95% CI: 0.62, 0.74), Por=7) at biopsy with AUC improving from 0.76 (95% CI: 0.64, 0.89) to 0.87 (95% CI: 0.81, 0.94), P=0.003). Application of the panel to 1000 men with persistently elevated PSA after initial negative biopsy, at a 15% risk threshold would reduce the number of biopsies by 712; would miss (or delay) the diagnosis of 53 cancers, of which only 3 would be Gleason 7 and the rest Gleason 6 or less. Our data constitute an external validation of a previously published model. The four-kallikrein panel predicts the result of repeat prostate biopsy in men with elevated PSA while dramatically decreasing unnecessary biopsies.

  1. Role of prostate specific antigen and immediate confirmatory biopsy in predicting progression during active surveillance for low risk prostate cancer.

    Science.gov (United States)

    Adamy, Ari; Yee, David S; Matsushita, Kazuhito; Maschino, Alexandra; Cronin, Angel; Vickers, Andrew; Guillonneau, Bertrand; Scardino, Peter T; Eastham, James A

    2011-02-01

    We evaluated predictors of progression after starting active surveillance, especially the role of prostate specific antigen and immediate confirmatory prostate biopsy. A total of 238 men with prostate cancer met active surveillance eligibility criteria and were analyzed for progression with time. Cox proportional hazards regression was used to evaluate predictors of progression. Progression was evaluated using 2 definitions, including no longer meeting 1) full and 2) modified criteria, excluding prostate specific antigen greater than 10 ng/ml as a criterion. Using full criteria 61 patients progressed during followup. The 2 and 5-year progression-free probability was 80% and 60%, respectively. With prostate specific antigen included in progression criteria prostate specific antigen at confirmatory biopsy (HR 1.29, 95% CI 1.14-1.46, p <0.0005) and positive confirmatory biopsy (HR 1.75, 95% CI 1.01-3.04, p = 0.047) were independent predictors of progression. Of the 61 cases 34 failed due to increased prostate specific antigen, including only 5 with subsequent progression by biopsy criteria. When prostate specific antigen was excluded from progression criteria, only 32 cases progressed, and 2 and 5-year progression-free probability was 91% and 76%, respectively. Using modified criteria as an end point positive confirmatory biopsy was the only independent predictor of progression (HR 3.16, 95% CI 1.41-7.09, p = 0.005). Active surveillance is feasible in patients with low risk prostate cancer and most patients show little evidence of progression within 5 years. There is no clear justification for treating patients in whom prostate specific antigen increases above 10 ng/ml in the absence of other indications of tumor progression. Patients considering active surveillance should undergo confirmatory biopsy to better assess the risk of progression. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  2. Validation of revised Epstein's criteria for insignificant prostate cancer prediction in a Greek subpopulation.

    Science.gov (United States)

    Chondros, Κ; Karpathakis, Ν; Heretis, Ι; Mavromanolakis, Ε; Chondros, N; Sofras, F; Mamoulakis, C

    2015-01-01

    Different treatment options for patients with prostate cancer (PCa) are applicable after stratifying patients according to various classification criteria. The purpose of our study is to evaluate the revised Epstein's criteria for insignificant PCa prediction in a Greek subpopulation. During a 4-year-period, 172 Cretan patients were submitted to radical retropubic prostatectomy in our institution. 23 out of them met the revised Epstein's criteria for the presence of clinically insignificant PCa (clinical stage T1c, prostate specific antigen density < 0.15 ng/ml/g, absence of Gleason pattern 4-5, <3 positive biopsy cores, presence of <50% tumor per core) during pre-treatment evaluation and were retrospectively included in the study. Post-surgery outcomes were evaluated including pathological stage, surgical margins and Gleason score upgrade. Organ confined disease and insignificant PCa were predicted with a 74% and 31% accuracy, respectively. These figures are remarkably lower than those derived from similar studies worldwide. Due to the high variation in the revised Epstein's criteria prediction accuracy observed worldwide, the development and implementation of novel tools/nomograms with a greater predictive accuracy is still warranted. Hippokratia 2015, 19 (1): 30-33.

  3. Determining if pretreatment PSA doubling time predicts PSA trajectories after radiation therapy for localized prostate cancer

    International Nuclear Information System (INIS)

    Soto, Daniel E.; Andridge, Rebecca R.; Pan, Charlie C.; Williams, Scott G.; Taylor, Jeremy M.G.; Sandler, Howard M.

    2009-01-01

    Introduction: To determine if pretreatment PSA doubling time (PSA-DT) can predict post-radiation therapy (RT) PSA trajectories for localized prostate cancer. Materials and methods: Three hundred and seventy-five prostate cancer patients treated with external beam RT without androgen deprivation therapy (ADT) were identified with an adequate number of PSA values. We utilized a linear mixed model (LMM) analysis to model longitudinal PSA data sets after definitive treatment. Post-treatment PSA trajectories were allowed to depend on the pre-RT PSA-DT, pre-RT PSA (iPSA), Gleason score (GS), and T-stage. Results: Pre-RT PSA-DT had a borderline impact on predicting the rate of PSA rise after nadir (p = 0.08). For a typical low risk patient (T1, GS ≤ 6, iPSA 10), the predicted PSA-DT post-nadir was 21% shorter for pre-RT PSA-DT 24 month (19 month vs. 24 month). Additional significant predictors of post-RT PSA rate of rise included GS (p < 0.0001), iPSA (p < 0.0001), and T-stage (p = 0.02). Conclusions: We observed a trend between rapidly rising pre-RT PSA and the post-RT post-nadir PSA rise. This effect appeared to be independent of iPSA, GS, or T-stage. The results presented suggest that pretreatment PSA-DT may help predict post-RT PSA trajectories

  4. Ghrelin O-acyltransferase (GOAT) is expressed in prostate cancer tissues and cell lines and expression is differentially regulated in vitro by ghrelin

    Science.gov (United States)

    2013-01-01

    Background Ghrelin is a 28 amino acid peptide hormone that is expressed in the stomach and a range of peripheral tissues, where it frequently acts as an autocrine/paracrine growth factor. Ghrelin is modified by a unique acylation required for it to activate its cognate receptor, the growth hormone secretagogue receptor (GHSR), which mediates many of the actions of ghrelin. Recently, the enzyme responsible for adding the fatty acid residue (octanoyl/acyl group) to the third amino acid of ghrelin, GOAT (ghrelin O-acyltransferase), was identified. Methods We used cell culture, quantitative real-time reverse transcription (RT)-PCR and immunohistochemistry to demonstrate the expression of GOAT in prostate cancer cell lines and tissues from patients. Real-time RT-PCR was used to demonstrate the expression of prohormone convertase (PC)1/3, PC2 and furin in prostate cancer cell lines. Prostate-derived cell lines were treated with ghrelin and desacyl ghrelin and the effect on GOAT expression was measured using quantitative RT-PCR. Results We have demonstrated that GOAT mRNA and protein are expressed in the normal prostate and human prostate cancer tissue samples. The RWPE-1 and RWPE-2 normal prostate-derived cell lines and the LNCaP, DU145, and PC3 prostate cancer cell lines express GOAT and at least one other enzyme that is necessary to produce mature, acylated ghrelin from proghrelin (PC1/3, PC2 or furin). Finally, ghrelin, but not desacyl ghrelin (unacylated ghrelin), can directly regulate the expression of GOAT in the RWPE-1 normal prostate derived cell line and the PC3 prostate cancer cell line. Ghrelin treatment (100nM) for 6 hours significantly decreased GOAT mRNA expression two-fold (P ghrelin did not regulate GOAT expression in the DU145 and LNCaP prostate cancer cell lines. Conclusions This study demonstrates that GOAT is expressed in prostate cancer specimens and cell lines. Ghrelin regulates GOAT expression, however, this is likely to be cell-type specific

  5. A predictive model to guide management of the overlap region between target volume and organs at risk in prostate cancer volumetric modulated arc therapy

    Energy Technology Data Exchange (ETDEWEB)

    Mattes, Malcolm D.; Lee, Jennifer C.; Einaiem, Sara; Guirguis, Adel; Ikoro, N. C.; Ashamalla Hani [Dept. of Radiation Oncology, New York Methodist Hospital, Brooklyn (United States)

    2013-12-15

    The goal of this study is to determine whether the magnitude of overlap between planning target volume (PTV) and rectum (Rectum{sub overlap}) or PTV and bladder (Bladder{sub overlap}) in prostate cancer volumetric-modulated arc therapy (VMAT) is predictive of the dose-volume relationships achieved after optimization, and to identify predictive equations and cutoff values using these overlap volumes beyond which the Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC) dose-volume constraints are unlikely to be met. Fifty-seven patients with prostate cancer underwent VMAT planning using identical optimization conditions and normalization. The PTV (for the 50.4 Gy primary plan and 30.6 Gy boost plan) included 5 to 10 mm margins around the prostate and seminal vesicles. Pearson correlations, linear regression analyses, and receiver operating characteristic (ROC) curves were used to correlate the percentage overlap with dose-volume parameters. The percentage Rectum{sub overlap} and Bladder{sub overlap} correlated with sparing of that organ but minimally impacted other dose-volume parameters, predicted the primary plan rectum V{sub 45} and bladder V{sub 50} with R{sup 2} = 0.78 and R{sup 2} = 0.83, respectively, and predicted the boost plan rectum V{sub 30} and bladder V{sub 30} with R{sup 2} = 0.53 and R{sup 2} = 0.81, respectively. The optimal cutoff value of boost Rectumoverlap to predict rectum V75 >15% was 3.5% (sensitivity 100%, specificity 94%, p < 0.01), and the optimal cutoff value of boost Bladder{sub overlap} to predict bladder V{sub 80} >10% was 5.0% (sensitivity 83%, specificity 100%, p < 0.01). The degree of overlap between PTV and bladder or rectum can be used to accurately guide physicians on the use of interventions to limit the extent of the overlap region prior to optimization.

  6. A predictive model to guide management of the overlap region between target volume and organs at risk in prostate cancer volumetric modulated arc therapy

    International Nuclear Information System (INIS)

    Mattes, Malcolm D.; Lee, Jennifer C.; Einaiem, Sara; Guirguis, Adel; Ikoro, N. C.; Ashamalla Hani

    2013-01-01

    The goal of this study is to determine whether the magnitude of overlap between planning target volume (PTV) and rectum (Rectum overlap ) or PTV and bladder (Bladder overlap ) in prostate cancer volumetric-modulated arc therapy (VMAT) is predictive of the dose-volume relationships achieved after optimization, and to identify predictive equations and cutoff values using these overlap volumes beyond which the Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC) dose-volume constraints are unlikely to be met. Fifty-seven patients with prostate cancer underwent VMAT planning using identical optimization conditions and normalization. The PTV (for the 50.4 Gy primary plan and 30.6 Gy boost plan) included 5 to 10 mm margins around the prostate and seminal vesicles. Pearson correlations, linear regression analyses, and receiver operating characteristic (ROC) curves were used to correlate the percentage overlap with dose-volume parameters. The percentage Rectum overlap and Bladder overlap correlated with sparing of that organ but minimally impacted other dose-volume parameters, predicted the primary plan rectum V 45 and bladder V 50 with R 2 = 0.78 and R 2 = 0.83, respectively, and predicted the boost plan rectum V 30 and bladder V 30 with R 2 = 0.53 and R 2 = 0.81, respectively. The optimal cutoff value of boost Rectumoverlap to predict rectum V75 >15% was 3.5% (sensitivity 100%, specificity 94%, p overlap to predict bladder V 80 >10% was 5.0% (sensitivity 83%, specificity 100%, p < 0.01). The degree of overlap between PTV and bladder or rectum can be used to accurately guide physicians on the use of interventions to limit the extent of the overlap region prior to optimization.

  7. Intraductal Carcinoma of the Prostate on Diagnostic Needle Biopsy Predicts Prostate Cancer Mortality: A Population-Based Study.

    Science.gov (United States)

    Saeter, Thorstein; Vlatkovic, Ljiljana; Waaler, Gudmund; Servoll, Einar; Nesland, Jahn M; Axcrona, Karol; Axcrona, Ulrika

    2017-06-01

    Intraductal carcinoma of the prostate (IDC-P) is a distinct histopathologic feature associated with high-grade, advanced prostate cancer. Although studies have shown that IDC-P is a predictor of progression following surgical or radiation treatment for prostate cancer, there are sparse data regarding IDC-P on diagnostic needle biopsy as a prognosticator of prostate cancer mortality. This was a population-based study of all prostate cancer patients diagnosed using needle biopsy and without evidence of systemic disease between 1991 and 1999 within a defined geographic region of Norway. Patients were identified by cross-referencing the Norwegian Cancer Registry. Of 318 eligible patients, 283 had biopsy specimens available for central pathology review. Clinical data were obtained from medical charts. We examined whether IDC-P on diagnostic needle biopsy was associated with adverse clinicopathological features and prostate cancer mortality. Patients with IDC-P on diagnostic needle biopsy had a more advanced stage and a higher Gleason score compared to patients without IDC-P. IDC-P was also associated with an intensively reactive stroma. The 10-year prostate cancer-specific survival was 69% for patients with IDC-P on diagnostic needle biopsy and 89% for patients without IDC-P (Log rank P-value prostate cancer mortality after adjustments for clinical prognostic factors and treatment. After adjustment for the newly implemented Grade Group system of prostate cancer, IDC-P showed a strong tendency toward statistical significance. However, IDC-P did not remain a statistically significant predictor in the multivariable analysis. IDC-P on diagnostic needle biopsy is an indicator of prostate cancer with a high risk of mortality. Accordingly, a diagnosis of IDC-P on needle biopsy should be reported and considered a feature of high-risk prostate cancer. Moreover, the association between IDC-P and reactive stroma provides evidence in support of the idea that stromal factors

  8. A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling.

    Science.gov (United States)

    Klein, Eric A; Cooperberg, Matthew R; Magi-Galluzzi, Cristina; Simko, Jeffry P; Falzarano, Sara M; Maddala, Tara; Chan, June M; Li, Jianbo; Cowan, Janet E; Tsiatis, Athanasios C; Cherbavaz, Diana B; Pelham, Robert J; Tenggara-Hunter, Imelda; Baehner, Frederick L; Knezevic, Dejan; Febbo, Phillip G; Shak, Steven; Kattan, Michael W; Lee, Mark; Carroll, Peter R

    2014-09-01

    .3-3.0; p=0.003) at surgical pathology. GPS predicted high-grade and/or high-stage disease after controlling for established clinical factors (p<0.005) such as an OR of 2.1 (95% CI, 1.4-3.2) when adjusting for Cancer of the Prostate Risk Assessment score. A limitation of the validation study was the inclusion of men with low-volume intermediate-risk PCa (Gleason score 3+4), for whom some providers would not consider AS. Genes representing multiple biological pathways discriminate PCa aggressiveness in biopsy tissue despite tumor heterogeneity, multifocality, and limited sampling at time of biopsy. The biopsy-based 17-gene GPS improves prediction of the presence or absence of adverse pathology and may help men with PCa make more informed decisions between AS and immediate treatment. Prostate cancer (PCa) is often present in multiple locations within the prostate and has variable characteristics. We identified genes with expression associated with aggressive PCa to develop a biopsy-based, multigene signature, the Genomic Prostate Score (GPS). GPS was validated for its ability to predict men who have high-grade or high-stage PCa at diagnosis and may help men diagnosed with PCa decide between active surveillance and immediate definitive treatment. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  9. Dosimetric impact of dual-energy CT tissue segmentation for low-energy prostate brachytherapy: a Monte Carlo study

    Science.gov (United States)

    Remy, Charlotte; Lalonde, Arthur; Béliveau-Nadeau, Dominic; Carrier, Jean-François; Bouchard, Hugo

    2018-01-01

    The purpose of this study is to evaluate the impact of a novel tissue characterization method using dual-energy over single-energy computed tomography (DECT and SECT) on Monte Carlo (MC) dose calculations for low-dose rate (LDR) prostate brachytherapy performed in a patient like geometry. A virtual patient geometry is created using contours from a real patient pelvis CT scan, where known elemental compositions and varying densities are overwritten in each voxel. A second phantom is made with additional calcifications. Both phantoms are the ground truth with which all results are compared. Simulated CT images are generated from them using attenuation coefficients taken from the XCOM database with a 100 kVp spectrum for SECT and 80 and 140Sn kVp for DECT. Tissue segmentation for Monte Carlo dose calculation is made using a stoichiometric calibration method for the simulated SECT images. For the DECT images, Bayesian eigentissue decomposition is used. A LDR prostate brachytherapy plan is defined with 125I sources and then calculated using the EGSnrc user-code Brachydose for each case. Dose distributions and dose-volume histograms (DVH) are compared to ground truth to assess the accuracy of tissue segmentation. For noiseless images, DECT-based tissue segmentation outperforms the SECT procedure with a root mean square error (RMS) on relative errors on dose distributions respectively of 2.39% versus 7.77%, and provides DVHs closest to the reference DVHs for all tissues. For a medium level of CT noise, Bayesian eigentissue decomposition still performs better on the overall dose calculation as the RMS error is found to be of 7.83% compared to 9.15% for SECT. Both methods give a similar DVH for the prostate while the DECT segmentation remains more accurate for organs at risk and in presence of calcifications, with less than 5% of RMS errors within the calcifications versus up to 154% for SECT. In a patient-like geometry, DECT-based tissue segmentation provides dose

  10. Postoperative Prostate-Specific Antigen Velocity Independently Predicts for Failure of Salvage Radiotherapy After Prostatectomy

    International Nuclear Information System (INIS)

    King, Christopher R.; Presti, Joseph C.; Brooks, James D.; Gill, Harcharan; Spiotto, Michael T.

    2008-01-01

    Purpose: Identification of patients most likely to benefit from salvage radiotherapy (RT) using postoperative (postop) prostate-specific antigen (PSA) kinetics. Methods and Materials: From 1984 to 2004, 81 patients who fit the following criteria formed the study population: undetectable PSA after radical prostatectomy (RP); pathologically negative nodes; biochemical relapse defined as a persistently detectable PSA; salvage RT; and two or more postop PSAs available before salvage RT. Salvage RT included the whole pelvic nodes in 55 patients and 4 months of total androgen suppression in 56 patients. The median follow-up was >5 years. All relapses were defined as a persistently detectable PSA. Kaplan-Meier and Cox proportional hazards multivariable analysis were performed for all clinical, pathological, and treatment factors predicting for biochemical relapse-free survival (bRFS). Results: There were 37 biochemical relapses observed after salvage RT. The 5-year bRFS after salvage RT for patients with postop prostate-specific antigen velocity ≤1 vs. >1 ng/ml/yr was 59% vs. 29%, p = 0.002. In multivariate analysis, only postop PSAV (p = 0.0036), pre-RT PSA level ≤1 (p = 0.037) and interval-to-relapse >10 months (p = 0.012) remained significant, whereas pelvic RT, hormone therapy, and RT dose showed a trend (p = ∼0.06). PSAV, but not prostate-specific antigen doubling time, predicted successful salvage RT, suggesting an association of zero-order kinetics with locally recurrent disease. Conclusions: Postoperative PSA velocity independently predicts for the failure of salvage RT and can be considered in addition to high-risk features when selecting patients in need of systemic therapy following biochemical failure after RP. For well-selected patients, salvage RT can achieve high cure rates

  11. SU-E-J-95: Predicting Treatment Outcomes for Prostate Cancer: Irradiation Responses of Prostate Cancer Stem Cells

    International Nuclear Information System (INIS)

    Wang, K

    2014-01-01

    Purpose: Most prostate cancers are slow-growing diseases but normally require much higher doses (80Gy) with conventional fractionation radiotherapy, comparing to other more aggressive cancers. This study is to disclose the radiobiological basis of this discrepancy by proposing the concept of prostate cancer stem cells (CSCs) and examining their specific irradiation responses. Methods: There are overwhelming evidences that CSC may keep their stemness, e.g. the competency of cell differentiation, in hypoxic microenvironments and hence become radiation resistive, though the probability is tiny for aggressiveness cancers. Tumor hypoxia used to be considered as an independent reason for poor treatment outcomes, and recent evidences showed that even prostate cancers were also hypoxic though they are very slow-growing. In addition, to achieve comparable outcomes to other much more aggressive cancers, much higher doses (rather than lower doses) are always needed for prostate cancers, regardless of its non-aggressiveness. All these abnormal facts can only be possibly interpreted by the irradiation responses characteristics of prostate CSCs. Results: Both normal cancer cells (NCCs) and CSCs exiting in tumors, in which NCCs are mainly for symptoms whereas killing all CSCs achieves disease-free. Since prostate cancers are slow-growing, the hypoxia in prostate cancers cannot possibly from NCCs, thus it is caused by hypoxic CSCs. However, single hypoxic cell cannot be imaged due to limitation of imaging techniques, unless a large group of hypoxic cells exist together, thus most of CSCs in prostate cancers are virtually hypoxic, i.e. not in working mode because CSCs in proliferating mode have to be normoxic, and this explains why prostate cancers are unaggressive. Conclusion: The fractional dose in conventional radiotherapy (∼2Gy) could only kill NCCs and CSCs in proliferating modes, whereas most CSCs survived fractional treatments since they were hypoxic, thus to eliminate all

  12. Benefits and harms of prostate cancer screening – predictions of the ONCOTYROL prostate cancer outcome and policy model

    Directory of Open Access Journals (Sweden)

    Nikolai Mühlberger

    2017-06-01

    Full Text Available Abstract Background A recent recalibration of the ONCOTYROL Prostate Cancer Outcome and Policy (PCOP Model, assuming that latent prostate cancer (PCa detectable at autopsy might be detectable by screening as well, resulted in considerable worsening of the benefit-harm balance of screening. In this study, we used the recalibrated model to assess the effects of familial risk, quality of life (QoL preferences, age, and active surveillance. Methods Men with average and elevated familial PCa risk were simulated in separate models, differing in familial risk parameters. Familial risk was assumed to affect PCa onset and progression simultaneously in the base-case, and separately in scenario analyses. Evaluated screening strategies included one-time screening at different ages, and screening at different intervals and age ranges. Optimal screening strategies were identified depending on age and individual QoL preferences. Strategies were additionally evaluated with active surveillance by biennial re-biopsy delaying treatment of localized cancer until grade progression to Gleason score ≥ 7. Results Screening men with average PCa risk reduced quality-adjusted life expectancy (QALE even under favorable assumptions. Men with elevated familial risk, depending on age and disutilities, gained QALE. While for men with familial risk aged 55 and 60 years annual screening to age 69 was the optimal strategy over most disutility ranges, no screening was the preferred option for 65 year-old men with average and above disutilities. Active surveillance greatly reduced overtreatment, but QALE gains by averted adverse events were opposed by losses due to delayed treatment and additional biopsies. The effect of active surveillance on the benefit-harm balance of screening differed between populations, as net losses and gains in QALE predicted for screening without active surveillance in men with average and familial PCa risk, respectively, were both reduced

  13. High SRPX2 protein expression predicts unfavorable clinical outcome in patients with prostate cancer

    Science.gov (United States)

    Zhang, Meng; Li, Xiaoli; Fan, Zhirui; Zhao, Jing; Liu, Shuzheng; Zhang, Mingzhi; Li, Huixiang; Goscinski, Mariusz Adam; Fan, Huijie; Suo, Zhenhe

    2018-01-01

    Background Sushi repeat-containing protein X-linked 2 (SRPX2) is overexpressed in a variety of different tumor tissues and correlated with poor prognosis in patients. Little research focuses on the role of SRPX2 expression in prostate cancer (PCa), and the clinicopathological significance of the protein expression in this tumor is relatively unknown. However, our previous transcriptome data from those cancer stem-like cells indicated the role of SRPX2 in PCa. Materials and methods In this study, RT-PCR and Western blotting were firstly used to examine the SRPX2 expression in three PCa cell lines including LNCaP, DU145, and PC3, and then SRPX2 protein expression was immunohistochemically investigated and statistically analyzed in a series of 106 paraffin-embedded PCa tissue specimens. Results Significantly lower levels of SRPX2 expression were verified in the LNCaP cells, compared with the expression in the aggressive DU145 and PC3 cells, in both mRNA and protein levels. Immunohistochemically, there were variable SRPX2 protein expressions in the clinical samples. Moreover, high levels of SRPX2 expression in the PCa tissues were significantly associated with Gleason score (P=0.008), lymph node metastasis (P=0.009), and distant metastasis (P=0.021). Furthermore, higher levels of SRPX2 expression in the PCa tissues were significantly associated with shorter overall survival (OS) (P<0.001). Conclusion Our results demonstrate that SRPX2 is highly expressed in aggressive PCa cells in vitro, and its protein expression in PCa is significantly associated with malignant clinical features and shorter OS, strongly indicating its prognostic value in prostate cancers. PMID:29881288

  14. urethral plasmakinetic resection of prostate on prostate- specific ...

    African Journals Online (AJOL)

    reduce blood flow in BPH, thereby preventing bleeding [6,7]. Thus ... urethra, prostate and surrounding tissue ... The peripheral blood and prostatic fluid of the patients ... Coronary heart ..... Length Density of Prostate Vessels, Intraoperative,.

  15. The Benefits of Including Clinical Factors in Rectal Normal Tissue Complication Probability Modeling After Radiotherapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Defraene, Gilles; Van den Bergh, Laura; Al-Mamgani, Abrahim; Haustermans, Karin; Heemsbergen, Wilma; Van den Heuvel, Frank; Lebesque, Joos V.

    2012-01-01

    Purpose: To study the impact of clinical predisposing factors on rectal normal tissue complication probability modeling using the updated results of the Dutch prostate dose-escalation trial. Methods and Materials: Toxicity data of 512 patients (conformally treated to 68 Gy [n = 284] and 78 Gy [n = 228]) with complete follow-up at 3 years after radiotherapy were studied. Scored end points were rectal bleeding, high stool frequency, and fecal incontinence. Two traditional dose-based models (Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) and a logistic model were fitted using a maximum likelihood approach. Furthermore, these model fits were improved by including the most significant clinical factors. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminating ability of all fits. Results: Including clinical factors significantly increased the predictive power of the models for all end points. In the optimal LKB, RS, and logistic models for rectal bleeding and fecal incontinence, the first significant (p = 0.011–0.013) clinical factor was “previous abdominal surgery.” As second significant (p = 0.012–0.016) factor, “cardiac history” was included in all three rectal bleeding fits, whereas including “diabetes” was significant (p = 0.039–0.048) in fecal incontinence modeling but only in the LKB and logistic models. High stool frequency fits only benefitted significantly (p = 0.003–0.006) from the inclusion of the baseline toxicity score. For all models rectal bleeding fits had the highest AUC (0.77) where it was 0.63 and 0.68 for high stool frequency and fecal incontinence, respectively. LKB and logistic model fits resulted in similar values for the volume parameter. The steepness parameter was somewhat higher in the logistic model, also resulting in a slightly lower D 50 . Anal wall DVHs were used for fecal incontinence, whereas anorectal wall dose best described the other two endpoints. Conclusions

  16. The Benefits of Including Clinical Factors in Rectal Normal Tissue Complication Probability Modeling After Radiotherapy for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Defraene, Gilles, E-mail: gilles.defraene@uzleuven.be [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Van den Bergh, Laura [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Al-Mamgani, Abrahim [Department of Radiation Oncology, Erasmus Medical Center - Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Haustermans, Karin [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Heemsbergen, Wilma [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Van den Heuvel, Frank [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Lebesque, Joos V. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)

    2012-03-01

    Purpose: To study the impact of clinical predisposing factors on rectal normal tissue complication probability modeling using the updated results of the Dutch prostate dose-escalation trial. Methods and Materials: Toxicity data of 512 patients (conformally treated to 68 Gy [n = 284] and 78 Gy [n = 228]) with complete follow-up at 3 years after radiotherapy were studied. Scored end points were rectal bleeding, high stool frequency, and fecal incontinence. Two traditional dose-based models (Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) and a logistic model were fitted using a maximum likelihood approach. Furthermore, these model fits were improved by including the most significant clinical factors. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminating ability of all fits. Results: Including clinical factors significantly increased the predictive power of the models for all end points. In the optimal LKB, RS, and logistic models for rectal bleeding and fecal incontinence, the first significant (p = 0.011-0.013) clinical factor was 'previous abdominal surgery.' As second significant (p = 0.012-0.016) factor, 'cardiac history' was included in all three rectal bleeding fits, whereas including 'diabetes' was significant (p = 0.039-0.048) in fecal incontinence modeling but only in the LKB and logistic models. High stool frequency fits only benefitted significantly (p = 0.003-0.006) from the inclusion of the baseline toxicity score. For all models rectal bleeding fits had the highest AUC (0.77) where it was 0.63 and 0.68 for high stool frequency and fecal incontinence, respectively. LKB and logistic model fits resulted in similar values for the volume parameter. The steepness parameter was somewhat higher in the logistic model, also resulting in a slightly lower D{sub 50}. Anal wall DVHs were used for fecal incontinence, whereas anorectal wall dose best described the other two endpoints

  17. An RNA-Based Digital Circulating Tumor Cell Signature Is Predictive of Drug Response and Early Dissemination in Prostate Cancer.

    Science.gov (United States)

    Miyamoto, David T; Lee, Richard J; Kalinich, Mark; LiCausi, Joseph A; Zheng, Yu; Chen, Tianqi; Milner, John D; Emmons, Erin; Ho, Uyen; Broderick, Katherine; Silva, Erin; Javaid, Sarah; Kwan, Tanya Todorova; Hong, Xin; Dahl, Douglas M; McGovern, Francis J; Efstathiou, Jason A; Smith, Matthew R; Sequist, Lecia V; Kapur, Ravi; Wu, Chin-Lee; Stott, Shannon L; Ting, David T; Giobbie-Hurder, Anita; Toner, Mehmet; Maheswaran, Shyamala; Haber, Daniel A

    2018-03-01

    Blood-based biomarkers are critical in metastatic prostate cancer, where characteristic bone metastases are not readily sampled, and they may enable risk stratification in localized disease. We established a sensitive and high-throughput strategy for analyzing prostate circulating tumor cells (CTC) using microfluidic cell enrichment followed by digital quantitation of prostate-derived transcripts. In a prospective study of 27 patients with metastatic castration-resistant prostate cancer treated with first-line abiraterone, pretreatment elevation of the digital CTC M score identifies a high-risk population with poor overall survival (HR = 6.0; P = 0.01) and short radiographic progression-free survival (HR = 3.2; P = 0.046). Expression of HOXB13 in CTCs identifies 6 of 6 patients with ≤12-month survival, with a subset also expressing the ARV7 splice variant. In a second cohort of 34 men with localized prostate cancer, an elevated preoperative CTC L score predicts microscopic dissemination to seminal vesicles and/or lymph nodes ( P digital quantitation of CTC-specific transcripts enables noninvasive monitoring that may guide treatment selection in both metastatic and localized prostate cancer. Significance: There is an unmet need for biomarkers to guide prostate cancer therapies, for curative treatment of localized cancer and for application of molecularly targeted agents in metastatic disease. Digital quantitation of prostate CTC-derived transcripts in blood specimens is predictive of abiraterone response in metastatic cancer and of early dissemination in localized cancer. Cancer Discov; 8(3); 288-303. ©2018 AACR. See related commentary by Heitzer and Speicher, p. 269 This article is highlighted in the In This Issue feature, p. 253 . ©2018 American Association for Cancer Research.

  18. Several genes encoding ribosomal proteins are over-expressed in prostate-cancer cell lines: confirmation of L7a and L37 over-expression in prostate-cancer tissue samples.

    Science.gov (United States)

    Vaarala, M H; Porvari, K S; Kyllönen, A P; Mustonen, M V; Lukkarinen, O; Vihko, P T

    1998-09-25

    A cDNA library specific for mRNA over-expressed in prostate cancer was generated by subtractive hybridization of transcripts originating from prostatic hyperplasia and cancer tissues. cDNA encoding ribosomal proteins L4, L5, L7a, L23a, L30, L37, S14 and S18 was found to be present among 100 analyzed clones. Levels of ribosomal mRNA were significantly higher at least in one of the prostate-cancer cell lines, LNCaP, DU-145 and PC-3, than in hyperplastic tissue, as determined by slot-blot hybridization. Furthermore, L23a- and S14-transcript levels were significantly elevated in PC-3 cells as compared with those in the normal prostate epithelial cell line PrEC. Generally, dramatic changes in the mRNA content of the ribosomal proteins were not detected, the most evident over-expression being that of L37 mRNA, which was 3.4 times more abundant in LNCaP cells than in hyperplastic prostate tissue. The over-expression of L7a and L37 mRNA was confirmed in prostate-cancer tissue samples by in situ hybridization. Elevated cancer-related expression of L4 and L30 has not been reported, but levels of the other ribosomal proteins are known to be increased in several types of cancers. These results therefore suggest that prostate cancer is comparable with other types of cancers, in that a larger pool of some ribosomal proteins is gained during the transformation process, by an unknown mechanism.

  19. Prostate Health Index (PHI) Predicts High-stage Pathology in African American Men.

    Science.gov (United States)

    Schwen, Zeyad R; Tosoian, Jeffrey J; Sokoll, Lori J; Mangold, Leslie; Humphreys, Elizabeth; Schaeffer, Edward M; Partin, Alan W; Ross, Ashley E

    2016-04-01

    To evaluate the association between the Prostate Health Index (PHI) and adverse pathology in a cohort of African American (AA) men undergoing radical prostatectomy. Eighty AA men with prostate-specific antigen (PSA) of 2-10 ng/mL underwent measurement of PSA, free PSA (fPSA), and p2PSA prior to radical prostatectomy. PHI was calculated as [(p2PSA/fPSA) × (PSA)(½)]. Biomarker association with pT3 disease was assessed using logistic regression, and covariates were added to a baseline multivariable model including digital rectal examination. Biomarker ability to predict pT3 disease was measured using the area under the receiver operator characteristic curve. Sixteen men (20%) demonstrated pT3 disease on final pathology. Mean age, PSA, and %fPSA were similar in men with and without pT3 disease (all P  >  .05), whereas PHI was significantly greater in men with pT3 disease (mean 57.2 vs 46.6, P  =  .04). Addition of PHI to the baseline multivariable model improved discriminative ability by 12.9% (P  =. .04) and yielded greater diagnostic accuracy than models, including other individual biomarkers. In AA men with PSA of 2-10 ng/mL, PHI was predictive of pT3 prostate cancer and may help to identify men at increased risk of adverse pathology. Additional studies are needed to substantiate these findings and identify appropriate thresholds for clinical use. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. First approach to studies of sulphur electron DOS in prostate cancer cell lines and tissues studied by XANES

    International Nuclear Information System (INIS)

    Kwiatek, Wojciech M.; Czapla, Joanna; Podgorczyk, Magdalena; Kisiel, Andrzej; Konior, Jerzy; Balerna, Antonella

    2011-01-01

    Urological cancers comprise approximately one-third of all cancers diagnosed in men worldwide and out of these, prostate cancer is the most common one (). Several risk factors such as age, hormone levels, environmental conditions and family history are suspected to play a role in the onset of this disease of otherwise obscure aetiology. It is therefore the medical need that drives multidisciplinary research in this field, carried out by means of various experimental and theoretical techniques. Out of many relevant factors, it is believed that sulphur can take an important part in cancer transformations. We have investigated the prostate cancer cell lines and tissues, along with selected organic and inorganic compounds used as references, by the X-ray absorption fine structure spectroscopy near the sulphur edge energy region. Particularly, the comparison of the experimental results collected during XANES measurements and theoretical calculations of electron density of states with use of the FEFF8 code and LAPW (linearised augmented plane-wave) method has been performed and in this work the first results of our studies are presented. - Highlights: → Different forms of sulphur has been found in prostate cancer cells. → FEFF8 code and LAPW method gave fairly good correspondence with the experiment. → LAPW is able to reproduce the fine structure of the absorption spectra. → Calculated DOS showed the influence of core atom on the shape of XANES spectra.

  1. Prostatectomy-based validation of combined urine and plasma test for predicting high grade prostate cancer.

    Science.gov (United States)

    Albitar, Maher; Ma, Wanlong; Lund, Lars; Shahbaba, Babak; Uchio, Edward; Feddersen, Søren; Moylan, Donald; Wojno, Kirk; Shore, Neal

    2018-03-01

    Distinguishing between low- and high-grade prostate cancers (PCa) is important, but biopsy may underestimate the actual grade of cancer. We have previously shown that urine/plasma-based prostate-specific biomarkers can predict high grade PCa. Our objective was to determine the accuracy of a test using cell-free RNA levels of biomarkers in predicting prostatectomy results. This multicenter community-based prospective study was conducted using urine/blood samples collected from 306 patients. All recruited patients were treatment-naïve, without metastases, and had been biopsied, designated a Gleason Score (GS) based on biopsy, and assigned to prostatectomy prior to participation in the study. The primary outcome measure was the urine/plasma test accuracy in predicting high grade PCa on prostatectomy compared with biopsy findings. Sensitivity and specificity were calculated using standard formulas, while comparisons between groups were performed using the Wilcoxon Rank Sum, Kruskal-Wallis, Chi-Square, and Fisher's exact test. GS as assigned by standard 10-12 core biopsies was 3 + 3 in 90 (29.4%), 3 + 4 in 122 (39.8%), 4 + 3 in 50 (16.3%), and > 4 + 3 in 44 (14.4%) patients. The urine/plasma assay confirmed a previous validation and was highly accurate in predicting the presence of high-grade PCa (Gleason ≥3 + 4) with sensitivity between 88% and 95% as verified by prostatectomy findings. GS was upgraded after prostatectomy in 27% of patients and downgraded in 12% of patients. This plasma/urine biomarker test accurately predicts high grade cancer as determined by prostatectomy with a sensitivity at 92-97%, while the sensitivity of core biopsies was 78%. © 2018 Wiley Periodicals, Inc.

  2. Comparison of prostate gene expression and tissue weight changes as monitors of antiandrogen activity in GNRH-inhibited rats

    DEFF Research Database (Denmark)

    Nellemann, Christine Lydia; Lefevre, P. A.; Ashby, J.

    2003-01-01

    and Pharmacology 34:188-203, 2001], and concomitantly described changes in expression of the androgen-dependent prostatic genes PBP C3, TRPM-2, and ODC as a possible complement to gravimetric analysis of the sex accessory tissues (SAT) [Nellemann C, Vinggaard AM, Dalgaard M, Hossaini A, Larsen J-J. Toxicology 163......:29-38, 2001]. METHODS: The present study describes the results of combining these two modifications into a single assay. During the course of these experiments it was shown that SD rats gave similar results to AP rats and that the higher stimulatory dose of testosterone propionate (TP) used in our experiments...

  3. SU-F-T-46: The Effect of Inter-Seed Attenuation and Tissue Composition in Prostate 125I Brachytherapy Dose Calculations

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, K; Araki, F; Ohno, T [Kumamoto University, Kumamoto, Kumamoto (Japan)

    2016-06-15

    Purpose: To investigate the difference of dose distributions with/without the effect of inter-seed attenuation and tissue compositions in prostate {sup 125}I brachytherapy dose calculations, using Monte Carlo simulations of Particle and Heavy Ion Transport code System (PHITS). Methods: The dose distributions in {sup 125}I prostate brachytherapy were calculated using PHITS for non-simultaneous and simultaneous alignments of STM1251 sources in water or prostate phantom for six patients. The PHITS input file was created from DICOM-RT file which includes source coordinates and structures for clinical target volume (CTV) and organs at risk (OARs) of urethra and rectum, using in-house Matlab software. Photon and electron cutoff energies were set to 1 keV and 100 MeV, respectively. The dose distributions were calculated with the kerma approximation and the voxel size of 1 × 1 × 1 mm{sup 3}. The number of incident photon was set to be the statistical uncertainty (1σ) of less than 1%. The effect of inter-seed attenuation and prostate tissue compositions was evaluated from dose volume histograms (DVHs) for each structure, by comparing to results of the AAPM TG-43 dose calculation (without the effect of inter-seed attenuation and prostate tissue compositions). Results: The dose reduction due to the inter-seed attenuation by source capsules was approximately 2% for CTV and OARs compared to those of TG-43. In additions, by considering prostate tissue composition, the D{sub 90} and V{sub 100} of CTV reduced by 6% and 1%, respectively. Conclusion: It needs to consider the dose reduction due to the inter-seed attenuation and tissue composition in prostate {sup 125}I brachytherapy dose calculations.

  4. Imaging and prostate cancer

    International Nuclear Information System (INIS)

    Schwartz, Lawrence H.

    1996-01-01

    prostate gland. Only recently have advances in dynamic contrast enhanced CT scanning demonstrated differences in the internal zonal architecture of the prostate gland. The sensitivity of staging of local spread of prostate cancer is variable ranging from 18% to 75%. Magnetic resonance imaging of the prostate gland is a relatively new technique for staging prostate cancer. There is excellent tissue contrast between prostate cancers in the peripheral zone and normal prostate tissue. Initial evaluation of MRI for staging prostate cancer was disappointing due to poor accuracy of MRI for evaluation of small structures such as the neurovascular bundles, using the body coil. Subsequently specialized receiver (surface) coils have been designed to allow high resolution imaging of the prostate and to assess for extracapsular extension of tumor. These coils may be placed within the rectum or wrapped around the anterior and posterior pelvic walls. Images obtained with the endorectal or phased array coils are of better quality as measured by signal-to-noise and improved resolution. Improved accuracy of 16% has been demonstrated with the endorectal coil. The overall accuracy of staging prostate cancers has been reported between 69% and 89%. In order to evaluate the prostate, T1 and T2-weighted images of the prostate gland are obtained. T1-weighted images are most useful for visualizing the neurovascular bundles. Extension of tumor into the neurovascular bundle is evident when there is obliteration of high signal intensity fat between the prostate and the neurovascular bundle. Zonal architecture and the presence of prostate cancer is assessed on the T2-weighted images. Prostate cancer generally appears as areas of low signal intensity on the T2-weighted images. The seminal vesicles are of intermediate signal on T1-weighted images and are high signal on T2-weighted images appearing as tubular structures. When prostate cancer invades the seminal vesicles the normal high signal of T2

  5. Prostate Cancer Predictive Simulation Modelling, Assessing the Risk Technique (PCP-SMART): Introduction and Initial Clinical Efficacy Evaluation Data Presentation of a Simple Novel Mathematical Simulation Modelling Method, Devised to Predict the Outcome of Prostate Biopsy on an Individual Basis.

    Science.gov (United States)

    Spyropoulos, Evangelos; Kotsiris, Dimitrios; Spyropoulos, Katherine; Panagopoulos, Aggelos; Galanakis, Ioannis; Mavrikos, Stamatios

    2017-02-01

    We developed a mathematical "prostate cancer (PCa) conditions simulating" predictive model (PCP-SMART), from which we derived a novel PCa predictor (prostate cancer risk determinator [PCRD] index) and a PCa risk equation. We used these to estimate the probability of finding PCa on prostate biopsy, on an individual basis. A total of 371 men who had undergone transrectal ultrasound-guided prostate biopsy were enrolled in the present study. Given that PCa risk relates to the total prostate-specific antigen (tPSA) level, age, prostate volume, free PSA (fPSA), fPSA/tPSA ratio, and PSA density and that tPSA ≥ 50 ng/mL has a 98.5% positive predictive value for a PCa diagnosis, we hypothesized that correlating 2 variables composed of 3 ratios (1, tPSA/age; 2, tPSA/prostate volume; and 3, fPSA/tPSA; 1 variable including the patient's tPSA and the other, a tPSA value of 50 ng/mL) could operate as a PCa conditions imitating/simulating model. Linear regression analysis was used to derive the coefficient of determination (R 2 ), termed the PCRD index. To estimate the PCRD index's predictive validity, we used the χ 2 test, multiple logistic regression analysis with PCa risk equation formation, calculation of test performance characteristics, and area under the receiver operating characteristic curve analysis using SPSS, version 22 (P regression revealed the PCRD index as an independent PCa predictor, and the formulated risk equation was 91% accurate in predicting the probability of finding PCa. On the receiver operating characteristic analysis, the PCRD index (area under the curve, 0.926) significantly (P < .001) outperformed other, established PCa predictors. The PCRD index effectively predicted the prostate biopsy outcome, correctly identifying 9 of 10 men who were eventually diagnosed with PCa and correctly ruling out PCa for 9 of 10 men who did not have PCa. Its predictive power significantly outperformed established PCa predictors, and the formulated risk equation

  6. Pretreatment Serum Cystatin C Levels Predict Renal Function, but Not Tumor Characteristics, in Patients with Prostate Neoplasia

    Directory of Open Access Journals (Sweden)

    Feilong Yang

    2017-01-01

    Full Text Available To evaluate the role of Cystatin C (Cys-C in tumorigenesis and progression of prostate cancer (PCa, we retrospectively collected the clinical information from the records of 492 benign prostatic hyperplasia (BPH, 48 prostatic intraepithelial neoplasia (PIN, and 173 PCa patients, whose disease was newly diagnosed and histologically confirmed. Pretreatment serum Cys-C levels were compared across the various groups and then analyzed to identify relationships, if any, with clinical and pathological characteristics of the PCa patient group. There were no significant differences in serum Cys-C levels among the three groups (P > 0.05. In PCa patients with normal SCr levels, patient age was correlated with serum Cys-C level (P ≤ 0.001 but did not correlate with alkaline phosphatase (AKP, lactate dehydrogenase (LDH, prostate specific antigen (PSA, Gleason score, or bone metastasis status (P > 0.05. Age and SCr contributed in part to the variations in serum Cys-C levels of PCa patients (r = 0.356, P ≤ 0.001; r = 0.520, P ≤ 0.001. In conclusion, serum Cys-C levels predict renal function in patients with prostate neoplasia, but were not a biomarker for the development of prostate neoplasia, and were not correlated with the clinicopathological characteristics of PCa.

  7. A framework for predicting three-dimensional prostate deformation in real time

    NARCIS (Netherlands)

    Jahya, Alex; Herink, Mark; Misra, Sarthak

    2013-01-01

    Background Surgical simulation systems can be used to estimate soft tissue deformation during pre- and intra-operative planning. Such systems require a model that can accurately predict the deformation in real time. In this study, we present a back-propagation neural network for predicting

  8. Prostate Ultrasound

    Medline Plus

    Full Text Available ... in which a needle is used to sample cells (tissue) from an abnormal area in the prostate ... needle insertion) is usually minimal because the rectal wall is relatively insensitive to the pain in the ...

  9. Blood flow responses to mild-intensity exercise in ectopic vs. orthotopic prostate tumors; dependence upon host tissue hemodynamics and vascular reactivity.

    Science.gov (United States)

    Garcia, Emmanuel; Becker, Veronika G C; McCullough, Danielle J; Stabley, John N; Gittemeier, Elizabeth M; Opoku-Acheampong, Alexander B; Sieman, Dietmar W; Behnke, Bradley J

    2016-07-01

    Given the critical role of tumor O2 delivery in patient prognosis and the rise in preclinical exercise oncology studies, we investigated tumor and host tissue blood flow at rest and during exercise as well as vascular reactivity using a rat prostate cancer model grown in two transplantation sites. In male COP/CrCrl rats, blood flow (via radiolabeled microspheres) to prostate tumors [R3327-MatLyLu cells injected in the left flank (ectopic) or ventral prostate (orthotopic)] and host tissue was measured at rest and during a bout of mild-intensity exercise. α-Adrenergic vasoconstriction to norepinephrine (NE: 10(-9) to 10(-4) M) was determined in arterioles perforating the tumors and host tissue. To determine host tissue exercise hyperemia in healthy tissue, a sham-operated group was included. Blood flow was lower at rest and during exercise in ectopic tumors and host tissue (subcutaneous adipose) vs. the orthotopic tumor and host tissue (prostate). During exercise, blood flow to the ectopic tumor significantly decreased by 25 ± 5% (SE), whereas flow to the orthotopic tumor increased by 181 ± 30%. Maximal vasoconstriction to NE was not different between arterioles from either tumor location. However, there was a significantly higher peak vasoconstriction to NE in subcutaneous adipose arterioles (92 ± 7%) vs. prostate arterioles (55 ± 7%). Establishment of the tumor did not alter host tissue blood flow from either location at rest or during exercise. These data demonstrate that blood flow in tumors is dependent on host tissue hemodynamics and that the location of the tumor may critically affect how exercise impacts the tumor microenvironment and treatment outcomes. Copyright © 2016 the American Physiological Society.

  10. Is intraoperative real-time dosimetry in prostate seed brachytherapy predictive of biochemical outcome?

    Directory of Open Access Journals (Sweden)

    Daniel Taussky

    2017-06-01

    Full Text Available Purpose : To analyze intraoperative (IO dosimetry using transrectal ultrasound (TRUS, performed before and after prostate low-dose-rate brachytherapy (LDR-BT, and compare it to dosimetry performed 30 days following the LDR-BT implant (Day 30. Material and methods : A total of 236 patients underwent prostate LDR-BT using 125 I that was performed with a three-dimensional TRUS-guided interactive inverse preplanning system (preimplant dosimetry. After the implant procedure, the TRUS was repeated in the operating room, and the dosimetry was recalculated (postimplant dosimetry and compared to dosimetry on Day 30 computed tomography (CT scans. Area under curve (AUC statistics was used for models predictive of dosimetric parameters at Day 30. Results : The median follow-up for patients without BF was 96 months, the 5-year and 8-year biochemical recurrence (BR-free rate was 96% and 90%, respectively. The postimplant median D 90 was 3.8 Gy lower (interquartile range [IQR], 12.4-0.9, and the V 100 only 1% less (IQR, 2.9-0.2% than the preimplant dosimetry. When comparing the postimplant and the Day 30 dosimetries, the postimplant median D 90 was 9.6 Gy higher (IQR [–] 9.5-30.3 Gy, and the V 100 was 3.2% greater (0.2-8.9% than Day 30 postimplant dosimetry. The variables that best predicted the D 90 of Day 30 was the postimplant D 90 (AUC = 0.62, p = 0.038. None of the analyzed values for IO or Day 30 dosimetry showed any predictive value for BR. Conclusions : Although improving the IO preimplant and postimplant dosimetry improved dosimetry on Day 30, the BR-free rate was not dependent on any dosimetric parameter. Unpredictable factors such as intraprostatic seed migration and IO factors, prevented the accurate prediction of Day 30 dosimetry.

  11. Preoperative nomograms incorporating magnetic resonance imaging and spectroscopy for prediction of insignificant prostate cancer

    Science.gov (United States)

    Shukla-Dave, Amita; Hricak, Hedvig; Akin, Oguz; Yu, Changhong; Zakian, Kristen L.; Udo, Kazuma; Scardino, Peter T.; Eastham, James; Kattan, Michael W.

    2011-01-01

    Objectives • To validate previously published nomograms for predicting insignificant prostate cancer (PCa) that incorporate clinical data, percentage of biopsy cores positive (%BC+) and magnetic resonance imaging (MRI) or MRI/MR spectroscopic imaging (MRSI) results. • We also designed new nomogram models incorporating magnetic resonance results and clinical data without detailed biopsy data. • Nomograms for predicting insignificant PCa can help physicians counsel patients with clinically low-risk disease who are choosing between active surveillance and definitive therapy. Patients and methods • In total, 181 low-risk PCa patients (clinical stage T1c–T2a, prostate-specific antigen level < 10 ng/mL, biopsy Gleason score of 6) had MRI/MRSI before surgery. • For MRI and MRI/MRSI, the probability of insignificant PCa was recorded prospectively and independently by two radiologists on a scale from 0 (definitely insignificant) to 3 (definitely significant PCa). • Insignificant PCa was defined on surgical pathology. • There were four models incorporating MRI or MRI/MRSI and clinical data with and without %BC+ that were compared with a base clinical model without %BC and a more comprehensive clinical model with %BC+. • Prediction accuracy was assessed using areas under receiver–operator characteristic curves. Results • At pathology, 27% of patients had insignificant PCa, and the Gleason score was upgraded in 56.4% of patients. • For both readers, all magnetic resonance models performed significantly better than the base clinical model (P ≤ 0.05 for all) and similarly to the more comprehensive clinical model. Conclusions • Existing models incorporating magnetic resonance data, clinical data and %BC+ for predicting the probability of insignificant PCa were validated. • All MR-inclusive models performed significantly better than the base clinical model. PMID:21933336

  12. Development of a Set of Nomograms to Predict Acute Lower Gastrointestinal Toxicity for Prostate Cancer 3D-CRT

    International Nuclear Information System (INIS)

    Valdagni, Riccardo; Rancati, Tiziana; Fiorino, Claudio; Fellin, Gianni; Magli, Alessandro; Baccolini, Michela; Bianchi, Carla; Cagna, Emanuela; Greco, Carlo; Mauro, Flora A.; Monti, Angelo F.; Munoz, Fernando; Stasi, Michele; Franzone, Paola; Vavassori, Vittorio

    2008-01-01

    Purpose: To predict acute Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) and Subjective Objective Signs Management and Analysis/Late Effect of Normal Tissue (SOMA/LENT) toxicities of the lower gastrointestinal (LGI) syndrome in patients with prostate cancer undergoing three-dimensional conformal radiotherapy using a tool (nomogram) that takes into account clinical and dosimetric variables that proved to be significant in the Italian Association for Radiation Oncology (AIRO) Group on Prostate Cancer (AIROPROS) 0102 trial. Methods and Materials: Acute rectal toxicity was scored in 1,132 patients by using both the RTOG/EORTC scoring system and a 10-item self-assessed questionnaire. Correlation between clinical variables/dose-volume histogram constraints and rectal toxicity was investigated by means of multivariate logistic analyses. Multivariate logistic analyses results were used to create nomograms predicting the symptoms of acute LGI syndrome. Results: Mean rectal dose was a strong predictor of Grade 2-3 RTOG/EORTC acute LGI toxicity (p 0.0004; odds ratio (OR) = 1.035), together with hemorrhoids (p = 0.02; OR 1.51), use of anticoagulants/antiaggregants (p = 0.02; OR = 0.63), and androgen deprivation (AD) (p = 0.04; OR = 0.65). Diabetes (p = 0.34; OR 1.28) and pelvic node irradiation (p = 0.11; OR = 1.56) were significant variables to adjust toxicity prediction. Bleeding was related to hemorrhoids (p = 0.02; OR = 173), AD (p = 0.17; OR = 0.67), and mean rectal dose (p 0.009; OR = 1.024). Stool frequency was related to seminal vesicle irradiation (p = 0.07; OR = 6.46), AD administered for more than 3 months (p = 0.002; OR = 0.32), and the percent volume of rectum receiving more than 60 Gy (V60Gy) V60 (p = 0.02; OR = 1.02). Severe fecal incontinence depended on seminal vesicle irradiation (p = 0.14; OR = 4.5) and V70 (p = 0.033; OR 1.029). Conclusions: To the best of our knowledge, this work presents the

  13. Early hematologic changes during prostate cancer radiotherapy predictive for late urinary and bowel toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Pinkawa, Michael; Djukic, Victoria; Klotz, Jens; Holy, Richard; Eble, Michael J. [RWTH Aachen University, Department of Radiation Oncology, Aachen (Germany); Ribbing, Carolina [RWTH Aachen University, Department of Diagnostic and Interventional Radiology, Aachen (Germany)

    2015-10-15

    The primary objective of the study was to identify early hematologic changes predictive for radiotherapy (RT)-associated genitourinary and gastrointestinal toxicity. In a group of 91 prostate cancer patients presenting for primary (n = 51) or postoperative (n = 40) curative RT, blood samples (blood count, acute phase proteins, and cytokines) were analyzed before (T1), three times during (T2-T4), and 6-8 weeks after (T5) radiotherapy. Before RT (baseline), on the last day (acute toxicity), a median of 2 months and 16 months (late toxicity) after RT, patients responded to a validated questionnaire (Expanded Prostate Cancer Index Composite). Acute score changes > 20 points and late changes > 10 points were considered clinically relevant. Radiotherapy resulted in significant changes of hematologic parameters, with the largest effect on lymphocytes (mean decrease of 31-45 %) and significant dependence on target volume. C-reactive protein (CRP) elevation > 5 mg/l and hemoglobin level decrease ≥ 5 G/1 at T2 were found to be independently predictive for acute urinary toxicity (p < 0.01, respectively). CRP elevation was predominantly detected in primary prostate RT (p = 0.02). Early lymphocyte level elevation ≥ 0.3G/l at T2 was protective against late urinary and bowel toxicity (p = 0.02, respectively). Other significant predictive factors for late bowel toxicity were decreasing hemoglobin levels (cut-off ≥ 5 G/l) at T2 (p = 0.04); changes of TNF-α (tumor necrosis factor; p = 0.03) and ferritin levels (p = 0.02) at T5. All patients with late bowel toxicity had interleukin (IL)-6 levels < 1.5 ng/l at T2 (63 % without; p = 0.01). Early hematologic changes during prostate cancer radiotherapy are predictive for late urinary and bowel toxicity. (orig.) [German] Das primaere Ziel der Studie war die Identifikation von fruehen haematologischen Veraenderungen mit praediktiver Bedeutung fuer radiotherapieassoziierte genitourinale und gastrointestinale Toxizitaet. In einer

  14. Unilateral Prostate Cancer Cannot be Accurately Predicted in Low-Risk Patients

    International Nuclear Information System (INIS)

    Isbarn, Hendrik; Karakiewicz, Pierre I.; Vogel, Susanne

    2010-01-01

    Purpose: Hemiablative therapy (HAT) is increasing in popularity for treatment of patients with low-risk prostate cancer (PCa). The validity of this therapeutic modality, which exclusively treats PCa within a single prostate lobe, rests on accurate staging. We tested the accuracy of unilaterally unremarkable biopsy findings in cases of low-risk PCa patients who are potential candidates for HAT. Methods and Materials: The study population consisted of 243 men with clinical stage ≤T2a, a prostate-specific antigen (PSA) concentration of <10 ng/ml, a biopsy-proven Gleason sum of ≤6, and a maximum of 2 ipsilateral positive biopsy results out of 10 or more cores. All men underwent a radical prostatectomy, and pathology stage was used as the gold standard. Univariable and multivariable logistic regression models were tested for significant predictors of unilateral, organ-confined PCa. These predictors consisted of PSA, %fPSA (defined as the quotient of free [uncomplexed] PSA divided by the total PSA), clinical stage (T2a vs. T1c), gland volume, and number of positive biopsy cores (2 vs. 1). Results: Despite unilateral stage at biopsy, bilateral or even non-organ-confined PCa was reported in 64% of all patients. In multivariable analyses, no variable could clearly and independently predict the presence of unilateral PCa. This was reflected in an overall accuracy of 58% (95% confidence interval, 50.6-65.8%). Conclusions: Two-thirds of patients with unilateral low-risk PCa, confirmed by clinical stage and biopsy findings, have bilateral or non-organ-confined PCa at radical prostatectomy. This alarming finding questions the safety and validity of HAT.

  15. Predictive Factors and Management of Rectal Bleeding Side Effects Following Prostate Cancer Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Price, Jeremy G. [Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York (United States); Stone, Nelson N. [Department of Urology, Icahn School of Medicine at Mount Sinai, New York, New York (United States); Stock, Richard G., E-mail: Richard.Stock@mountsinai.org [Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York (United States)

    2013-08-01

    Purpose: To report on the incidence, nature, and management of rectal toxicities following individual or combination brachytherapy following treatment for prostate cancer over a 17-year period. We also report the patient and treatment factors predisposing to acute ≥grade 2 proctitis. Methods and Materials: A total of 2752 patients were treated for prostate cancer between October 1990 and April 2007 with either low-dose-rate brachytherapy alone or in combination with androgen depletion therapy (ADT) or external beam radiation therapy (EBRT) and were followed for a median of 5.86 years (minimum 1.0 years; maximum 19.19 years). We investigated the 10-year incidence, nature, and treatment of acute and chronic rectal toxicities following BT. Using univariate, and multivariate analyses, we determined the treatment and comorbidity factors predisposing to rectal toxicities. We also outline the most common and effective management for these toxicities. Results: Actuarial risk of ≥grade 2 rectal bleeding was 6.4%, though notably only 0.9% of all patients required medical intervention to manage this toxicity. The majority of rectal bleeding episodes (72%) occurred within the first 3 years following placement of BT seeds. Of the 27 patients requiring management for their rectal bleeding, 18 underwent formalin treatment and nine underwent cauterization. Post-hoc univariate statistical analysis revealed that coronary artery disease (CAD), biologically effective dose, rectal volume receiving 100% of the prescription dose (RV100), and treatment modality predict the likelihood of grade ≥2 rectal bleeding. Only CAD, treatment type, and RV100 fit a Cox regression multivariate model. Conclusions: Low-dose-rate prostate brachytherapy is very well tolerated and rectal bleeding toxicities are either self-resolving or effectively managed by medical intervention. Treatment planning incorporating adjuvant ADT while minimizing RV100 has yielded the best toxicity-free survival following

  16. Prostate specific membrane antigen (PSMA) is a tissue-specific target for adenoviral transduction of prostate cancer in vitro

    NARCIS (Netherlands)

    Kraaij, R; van Rijswijk, ALCT; Haisma, HJ; Bangma, CH

    2005-01-01

    BACKGROUND. Adenovirus binds to the coxsackievirus and adenovirus receptor (CAR) as a first step in the process of cellular infection. This dependence on CAR potentially limits the use of adenovirus in gene therapy, since CAR is expressed in many tissues of the body, and, expression of CAR may be

  17. Understanding PSA and its derivatives in prediction of tumor volume: Addressing health disparities in prostate cancer risk stratification.

    Science.gov (United States)

    Chinea, Felix M; Lyapichev, Kirill; Epstein, Jonathan I; Kwon, Deukwoo; Smith, Paul Taylor; Pollack, Alan; Cote, Richard J; Kryvenko, Oleksandr N

    2017-03-28

    To address health disparities in risk stratification of U.S. Hispanic/Latino men by characterizing influences of prostate weight, body mass index, and race/ethnicity on the correlation of PSA derivatives with Gleason score 6 (Grade Group 1) tumor volume in a diverse cohort. Using published PSA density and PSA mass density cutoff values, men with higher body mass indices and prostate weights were less likely to have a tumor volume PSA derivatives when predicting for tumor volume. In receiver operator characteristic analysis, area under the curve values for all PSA derivatives varied across race/ethnicity with lower optimal cutoff values for Hispanic/Latino (PSA=2.79, PSA density=0.06, PSA mass=0.37, PSA mass density=0.011) and Non-Hispanic Black (PSA=3.75, PSA density=0.07, PSA mass=0.46, PSA mass density=0.008) compared to Non-Hispanic White men (PSA=4.20, PSA density=0.11 PSA mass=0.53, PSA mass density=0.014). We retrospectively analyzed 589 patients with low-risk prostate cancer at radical prostatectomy. Pre-operative PSA, patient height, body weight, and prostate weight were used to calculate all PSA derivatives. Receiver operating characteristic curves were constructed for each PSA derivative per racial/ethnic group to establish optimal cutoff values predicting for tumor volume ≥0.5 cm3. Increasing prostate weight and body mass index negatively influence PSA derivatives for predicting tumor volume. PSA derivatives' ability to predict tumor volume varies significantly across race/ethnicity. Hispanic/Latino and Non-Hispanic Black men have lower optimal cutoff values for all PSA derivatives, which may impact risk assessment for prostate cancer.

  18. Overexpression of the novel senescence marker β-galactosidase (GLB1 in prostate cancer predicts reduced PSA recurrence.

    Directory of Open Access Journals (Sweden)

    Jennifer Wagner

    Full Text Available Senescence is a terminal growth arrest that functions as a tumor suppressor in aging and precancerous cells and is a response to selected anticancer compounds. Lysosomal-β-galactosidase (GLB1 hydrolyzes β-galactose from glycoconjugates and is the origin of senescence-associated β-gal activity (SA-β-gal. Using a new GLB1 antibody, senescence biology was investigated in prostate cancer (PCa tissues.In vitro characterization of GLB1 was determined in primary prostate epithelial cell cultures passaged to replicative senescence and in therapy-induced senescence in PCa lines using chemotherapeutic agents. FFPE tissue microarrays were subjected to immunofluorescent staining for GLB1, Ki67 and HP1γ and automated quantitative imaging initially using AQUA in exploratory samples and Vectra in a validation series.GLB1 expression accumulates in replicative and induced senescence and correlates with senescent morphology and P16 (CDKN2 expression. In tissue arrays, quantitative imaging detects increased GLB1 expression in high-grade prostatic intraepithelial neoplasia (HGPIN, known to contain senescent cells, and cancer compared to benign prostate tissues (p<0.01 and senescent cells contain low Ki67 and elevated HP1γ. Within primary tumors, elevated GLB1 associates with lower T stage (p=0.01, localized versus metastatic disease (p=0.0003 and improved PSA-free survival (p=0.03. Increased GLB1 stratifies better PSA-free survival in intermediate grade PCa (0.01. Tissues that elaborate higher GLB1 display increased uniformity of expression.Increased GLB1 is a valuable marker in formalin-fixed paraffin-embedded (FFPE tissues for the senescence-like phenotype and associates with improved cancer outcomes. This protein addresses a lack of senescence markers and should be applicable to study the biologic role of senescence in other cancers.

  19. High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression

    Directory of Open Access Journals (Sweden)

    Bjartell Anders

    2011-09-01

    Full Text Available Abstract Background High expression of the RNA-binding protein RBM3 has previously been found to be associated with good prognosis in breast cancer, ovarian cancer, malignant melanoma and colorectal cancer. The aim of this study was to examine the prognostic impact of immunohistochemical RBM3 expression in prostate cancer. Findings Immunohistochemical RBM3 expression was examined in a tissue microarray with malignant and benign prostatic specimens from 88 patients treated with radical prostatectomy for localized disease. While rarely expressed in benign prostate gland epithelium, RBM3 was found to be up-regulated in prostate intraepithelial neoplasia and present in various fractions and intensities in invasive prostate cancer. High nuclear RBM3 expression was significantly associated with a prolonged time to biochemical recurrence (BCR (HR 0.56, 95% CI: 0.34-0.93, p = 0.024 and clinical progression (HR 0.09, 95% CI: 0.01-0.71, p = 0.021. These associations remained significant in multivariate analysis, adjusted for preoperative PSA level in blood, pathological Gleason score and presence or absence of extracapsular extension, seminal vesicle invasion and positive surgical margin (HR 0.41, 95% CI: 0.19-0.89, p = 0.024 for BCR and HR 0.06, 95% CI: 0.01-0.50, p = 0.009 for clinical progression. Conclusion Our results demonstrate that high nuclear expression of RBM3 in prostate cancer is associated with a prolonged time to disease progression and, thus, a potential biomarker of favourable prognosis. The value of RBM3 for prognostication, treatment stratification and follow-up of prostate cancer patients should be further validated in larger studies.

  20. Quantitative PET Imaging with Novel HER3-Targeted Peptides Selected by Phage Display to Predict Androgen-Independent Prostate Cancer Progression

    Science.gov (United States)

    2017-12-01

    Independent Prostate Cancer Progression PRINCIPAL INVESTIGATOR: Benjamin Larimer, PhD CONTRACTING ORGANIZATION: Massachusetts General Hospital Boston...TYPE Final 3. DATES COVERED 1 Aug 2016 – 19 August 2017 Selected by Phage Display to Predict Androgen-Independent Prostate Cancer Progression 5a...highly specific peptide that targets HER3 for prostate cancer imaging. The peptide was labeled with a PET imaging radionuclide and injected into mice

  1. Molecular profiling of prostate cancer derived exosomes may reveal a predictive signature for response to docetaxel.

    Science.gov (United States)

    Kharaziha, Pedram; Chioureas, Dimitris; Rutishauser, Dorothea; Baltatzis, George; Lennartsson, Lena; Fonseca, Pedro; Azimi, Alireza; Hultenby, Kjell; Zubarev, Roman; Ullén, Anders; Yachnin, Jeffrey; Nilsson, Sten; Panaretakis, Theocharis

    2015-08-28

    Docetaxel is a cornerstone treatment for metastatic, castration resistant prostate cancer (CRPC) which remains a leading cause of cancer-related deaths, worldwide. The clinical usage of docetaxel has resulted in modest gains in survival, primarily due to the development of resistance. There are currently no clinical biomarkers available that predict whether a CRPC patient will respond or acquire resistance to this therapy. Comparative proteomics analysis of exosomes secreted from DU145 prostate cancer cells that are sensitive (DU145 Tax-Sen) or have acquired resistance (DU145 Tax-Res) to docetaxel, demonstrated significant differences in the amount of exosomes secreted and in their molecular composition. A panel of proteins was identified by proteomics to be differentially enriched in DU145 Tax-Res compared to DU145 Tax-Sen exosomes and was validated by western blotting. Importantly, we identified MDR-1, MDR-3, Endophilin-A2 and PABP4 that were enriched only in DU145 Tax-Res exosomes. We validated the presence of these proteins in the serum of a small cohort of patients. DU145 cells that have uptaken DU145 Tax-Res exosomes show properties of increased matrix degradation. In summary, exosomes derived from DU145 Tax-Res cells may be a valuable source of biomarkers for response to therapy.

  2. Radioimmunoassay for a human prostate specific antigen

    International Nuclear Information System (INIS)

    Machida, T.; Miki, M.; Ohishi, Y.; Kido, A.; Morikawa, J.; Ogawa, Y.

    1983-01-01

    As a marker for prostatic cancer, a prostate-specific antigen was purified from human prostatic tissues. Double antibody radioimmunoassay utilizing immune reaction was developed on the basis of the purified prostatic antigen (PA). Measurement results have revealed that PA radioimmunoassay is much better than prostatic acid phosphatase (PAP) radioimmunoassay in the diagnosis of prostatic cancer

  3. Improving the Prediction of Prostate Cancer Overall Survival by Supplementing Readily Available Clinical Data with Gene Expression Levels of IGFBP3 and F3 in Formalin-Fixed Paraffin Embedded Core Needle Biopsy Material.

    Directory of Open Access Journals (Sweden)

    Zhuochun Peng

    Full Text Available A previously reported expression signature of three genes (IGFBP3, F3 and VGLL3 was shown to have potential prognostic value in estimating overall and cancer-specific survivals at diagnosis of prostate cancer in a pilot cohort study using freshly frozen Fine Needle Aspiration (FNA samples.We carried out a new cohort study with 241 prostate cancer patients diagnosed from 2004-2007 with a follow-up exceeding 6 years in order to verify the prognostic value of gene expression signature in formalin fixed paraffin embedded (FFPE prostate core needle biopsy tissue samples. The cohort consisted of four patient groups with different survival times and death causes. A four multiplex one-step RT-qPCR test kit, designed and optimized for measuring the expression signature in FFPE core needle biopsy samples, was used. In archive FFPE biopsy samples the expression differences of two genes (IGFBP3 and F3 were measured. The survival time predictions using the current clinical parameters only, such as age at diagnosis, Gleason score, PSA value and tumor stage, and clinical parameters supplemented with the expression levels of IGFBP3 and F3, were compared.When combined with currently used clinical parameters, the gene expression levels of IGFBP3 and F3 are improving the prediction of survival time as compared to using clinical parameters alone.The assessment of IGFBP3 and F3 gene expression levels in FFPE prostate cancer tissue would provide an improved survival prediction for prostate cancer patients at the time of diagnosis.

  4. Prediction of individual genetic risk to prostate cancer using a polygenic score

    DEFF Research Database (Denmark)

    Szulkin, Robert; Whitington, Thomas; Eklund, Martin

    2015-01-01

    BACKGROUND: Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate ca...

  5. A Double Blind, Randomized, Neoadjuvant Study of the Tissue effects of POMx Pills in Men with Prostate Cancer Prior to Radical Prostatectomy

    Science.gov (United States)

    Freedland, Stephen J.; Carducci, Michael; Kroeger, Nils; Partin, Alan; Rao, Jian-yu; Jin, Yusheng; Kerkoutian, Susan; Wu, Hong; Li, Yunfeng; Creel, Patricia; Mundy, Kelly; Gurganus, Robin; Fedor, Helen; King, Serina A.; Zhang, Yanjun; Heber, David; Pantuck, Allan J.

    2013-01-01

    Pomegranates slow prostate cancer xenograft growth and prolong PSA doubling times in single-arm human studies. Pomegranates’ effects on human prostate tissue are understudied. We hypothesized orally administered pomegranate extract (POMx; PomWonderful, Los Angeles, CA) would lower tissue 8-hydroxy-2-deoxyguanosine (8-OHdG), an oxidative stress biomarker. 70 men were randomized to 2 tablets POMx or placebo daily up to 4 weeks prior to radical prostatectomy. Tissue was analyzed for intra-prostatic Urolithin A, a pomegranate metabolite, benign and malignant 8-OHdG, and cancer pS6 kinase, NFκB, and Ki67. Primary end-point was differences in 8-OHdG powered to detect 30% reduction. POMx was associated with 16% lower benign tissue 8-OHdG (p=0.095), which was not statistically significant. POMx was well-tolerated with no treatment-related withdrawals. There were no differences in baseline clinicopathological features between arms. Urolithin A was detected in 21/33 patient in the POMx group vs. 12/35 in the placebo group (p=0.031). Cancer pS6 kinase, NFκB, Ki67, and serum PSA changes were similar between arms. POMx prior to surgery results in pomegranate metabolite accumulation in prostate tissues. Our primary end-point in this modest-sized short-term trial was negative. Future larger longer studies are needed to more definitely test whether POMx reduces prostate oxidative stress as well as further animal testing to better understand the multiple mechanisms through which POMx may alter prostate cancer biology. PMID:23985577

  6. Can pre-operative contrast-enhanced dynamic MR imaging for prostate cancer predict microvessel density in prostatectomy specimens?

    Energy Technology Data Exchange (ETDEWEB)

    Schlemmer, Heinz-Peter [Department of Oncological Diagnostics and Therapy, German Cancer Research Center, University Hospital Mannheim, Ruprecht Karls University, Heidelberg (Germany); Department of Diagnostic Radiology, University Hospital Tuebingen, Hoppe-Seyler-Strasse 3, 72076, Tuebingen (Germany); Merkle, Jonas; Kaick, Gerhard van [Department of Oncological Diagnostics and Therapy, German Cancer Research Center, University Hospital Mannheim, Ruprecht Karls University, Heidelberg (Germany); Grobholz, Rainer [Department of Pathology, University Hospital Mannheim, Ruprecht Karls University, Heidelberg (Germany); Jaeger, Tim; Michel, Maurice Stephan [Department of Urology, University Hospital Mannheim, Ruprecht Karls University, Heidelberg (Germany); Werner, Axel; Rabe, Jan [Department of Diagnostic Radiology, University Hospital Mannheim, Ruprecht Karls University, Heidelberg (Germany)

    2004-02-01

    The aim of this study was to correlate quantitative dynamic contrast-enhanced MRI (DCE MRI) parameters with microvessel density (MVD) in prostate carcinoma. Twenty-eight patients with biopsy-proven prostate carcinoma were examined by endorectal MRI including multiplanar T2- and T1-weighted spin-echo and dynamic T1-weighted turbo-FLASH MRI during and after intravenous Gd-DTPA administration. Microvessels were stained on surgical specimens using a CD31 monoclonal antibody. The MVD was quantified in hot spots by counting (MVC) and determining the area fraction by morphometry (MVAF). The DCE MRI data were analyzed using an open pharmacokinetic two-compartment model. In corresponding anatomic locations the time shift ({delta}t) between the beginning of signal enhancement of cancer and adjacent normal prostatic tissue, the degree of contrast enhancement and the contrast exchange rate constant (k{sub 21}) were calculated. The MVC and MVAF were elevated in carcinoma (p<0.001 and p=0.002, respectively) and correlated to k{sub 21} (r=0.62, p<0.001 and r=0.80, p<0.001, respectively). k{sub 21}-values of carcinoma were significantly higher compared with normal peripheral but not central zone tissue. {delta}t was longer in high compared with low-grade tumors (p=0.025). The DCE MRI can provide important information about individual MVD in prostate cancer, which may be helpful for guiding biopsy and assessing individual prognosis. (orig.)

  7. The evaluation of tissue mass loss in the incision line of prostate with benign hyperplasia performed using holmium laser and cutting electrode.

    Science.gov (United States)

    Szewczyk, Mariusz; Jesionek-Kupnicka, Dorota; Lipiński, Marek Ireneusz; Lipinski, Piotr; Różański, Waldemar

    2014-01-01

    The aim of this study is to compare the changes in the incision line of prostatic adenoma using a monopolar cutting electrode and holmium laser, as well as the assessment of associated tissue mass and volume loss of benign prostatic hyperplasia (BPH). The material used in this study consisted of 74 preparations of prostatic adenoma obtained via open retropubic adenomectomy, with an average volume of 120.7 ml. The material obtained cut in vitro before fixation in formaldehyde. One lobe was cut using holmium laser, the other using a monopolar cutting electrode. After the incision was made, tissue mass and volume loss were evaluated. Thermocoagulation changes in the incision line were examinedunder light microscope. In the case of the holmium laser incision, the average tissue mass loss was 1.73 g, tissue volume loss 3.57 ml and the depth of thermocoagulation was 1.17 mm. When the monopolar cutting electrode was used average tissue mass loss was 0.807 g, tissue volume loss 2.48 ml and the depth of thermocoagulation was 0.19 mm. Where holmium laser was used, it was observed that the layer of tissue with thermocoagulation changes was deeper than in the case of the monopolar cutting electrode. Moreover, it was noticed that holmium laser caused bigger tissue mass and volume loss than the cutting electrode.

  8. External Beam Radiation Therapy and Abiraterone in Men With Localized Prostate Cancer: Safety and Effect on Tissue Androgens

    International Nuclear Information System (INIS)

    Cho, Eunpi; Mostaghel, Elahe A.; Russell, Kenneth J.; Liao, Jay J.; Konodi, Mark A.; Kurland, Brenda F.; Marck, Brett T.; Matsumoto, Alvin M.; Dalkin, Bruce L.; Montgomery, R. Bruce

    2015-01-01

    Purpose: Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation therapy with definitive radiation therapy in men with locally advanced or high-grade disease. Addition of abiraterone to luteinizing hormone-releasing hormone agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression. Methods and Materials: A prospective, phase 2 study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at the discretion of the treating clinician. Prostate biopsy assays were obtained prior to the start of therapy and prior to radiation. Sera and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry. Results: A total of 22 men with intermediate- (n=3) and high-risk PCa (n=19) received study therapy. Sixteen men completed the intended course of abiraterone, and 19 men completed planned radiation to 77.4 to 81 Gy. Radiation to pelvic nodes was administered in 20 men. The following grade 3 toxicities were reported: lymphopenia (14 patients), fatigue (1 patient), transaminitis (2 patients), hypertension (2 patients), and hypokalemia (1 patient). There were no grade 4 toxicities. All 21 men who complied with at least 3 months of abiraterone therapy had a preradiation prostate-specific antigen (PSA) concentration nadir of <0.3 ng/mL. Median levels of tissue androgen downstream of CYP17A were significantly suppressed after treatment with abiraterone, and upstream steroids were increased. At median follow-up of 21 months (range: 3-37 months), only 1 patient (who had discontinued abiraterone at 3 months) had biochemical relapse. Conclusions: Addition of abiraterone to LHRHa with radiation is safe and achieves effective prostatic androgen suppression

  9. External Beam Radiation Therapy and Abiraterone in Men With Localized Prostate Cancer: Safety and Effect on Tissue Androgens

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Eunpi [University of Washington School of Medicine, Seattle, Washington (United States); Fred Hutchinson Cancer Research Center, Seattle, Washington (United States); Mostaghel, Elahe A. [Fred Hutchinson Cancer Research Center, Seattle, Washington (United States); Russell, Kenneth J.; Liao, Jay J.; Konodi, Mark A. [University of Washington School of Medicine, Seattle, Washington (United States); Kurland, Brenda F. [University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Marck, Brett T. [Veterans Affairs Puget Sound Health Care System, Seattle, Washington (United States); Matsumoto, Alvin M. [University of Washington School of Medicine, Seattle, Washington (United States); Veterans Affairs Puget Sound Health Care System, Seattle, Washington (United States); Dalkin, Bruce L. [University of Washington School of Medicine, Seattle, Washington (United States); Montgomery, R. Bruce, E-mail: rbmontgo@uw.edu [University of Washington School of Medicine, Seattle, Washington (United States)

    2015-06-01

    Purpose: Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation therapy with definitive radiation therapy in men with locally advanced or high-grade disease. Addition of abiraterone to luteinizing hormone-releasing hormone agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression. Methods and Materials: A prospective, phase 2 study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at the discretion of the treating clinician. Prostate biopsy assays were obtained prior to the start of therapy and prior to radiation. Sera and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry. Results: A total of 22 men with intermediate- (n=3) and high-risk PCa (n=19) received study therapy. Sixteen men completed the intended course of abiraterone, and 19 men completed planned radiation to 77.4 to 81 Gy. Radiation to pelvic nodes was administered in 20 men. The following grade 3 toxicities were reported: lymphopenia (14 patients), fatigue (1 patient), transaminitis (2 patients), hypertension (2 patients), and hypokalemia (1 patient). There were no grade 4 toxicities. All 21 men who complied with at least 3 months of abiraterone therapy had a preradiation prostate-specific antigen (PSA) concentration nadir of <0.3 ng/mL. Median levels of tissue androgen downstream of CYP17A were significantly suppressed after treatment with abiraterone, and upstream steroids were increased. At median follow-up of 21 months (range: 3-37 months), only 1 patient (who had discontinued abiraterone at 3 months) had biochemical relapse. Conclusions: Addition of abiraterone to LHRHa with radiation is safe and achieves effective prostatic androgen suppression

  10. Negative predictive value of multiparametric MRI for prostate cancer detection: Outcome of 5-year follow-up in men with negative findings on initial MRI studies

    Energy Technology Data Exchange (ETDEWEB)

    Itatani, R., E-mail: banguliao@gmail.com [Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Kumamoto 860-8556 (Japan); Department of Radiology, Kumamoto Chuo Hospital, 1-5-1, Tainoshima, Kumamoto 862-0965 (Japan); Namimoto, T. [Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Kumamoto 860-8556 (Japan); Atsuji, S.; Katahira, K.; Morishita, S. [Department of Radiology, Kumamoto Chuo Hospital, 1-5-1, Tainoshima, Kumamoto 862-0965 (Japan); Kitani, K.; Hamada, Y. [Department of Urology, Kumamoto Chuo Hospital, 1-5-1, Tainoshima, Kumamoto 862-0965 (Japan); Kitaoka, M. [Department of Pathology, Kumamoto Chuo Hospital, 1-5-1, Tainoshima, Kumamoto 862-0965 (Japan); Nakaura, T. [Department of Diagnostic Radiology, Amakusa Medical Center, Kameba 854-1, Amakusa, Kumamoto 863-0046 (Japan); Yamashita, Y. [Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Kumamoto 860-8556 (Japan)

    2014-10-15

    Highlights: • We assess the negative predictive value of multiparametric MRI for prostate cancer. • Patients with positive prostate biopsy findings were defined as false-negative. • Patients with negative initial prostate biopsy findings were followed up for 5 years. • The negative predictive value was 89.6% for significant prostate cancer. • MRI is a useful tool to rule out significant prostate cancer before biopsy. - Abstract: Objective: To assess the clinical negative predictive value (NPV) of multiparametric MRI (mp-MRI) for prostate cancer in a 5-year follow-up. Materials and methods: One hundred ninety-three men suspected of harboring prostate cancer with negative MRI findings were included. Patients with positive transrectal ultrasound (TRUS)-guided biopsy findings were defined as false-negative. Patients with negative initial TRUS-guided biopsy findings were followed up and only patients with negative findings by digital rectal examination, MRI, and repeat biopsy and no increase in PSA at 5-year follow-up were defined as “clinically negative”. The clinical NPV of mp-MRI was calculated. For quantitative analysis, mean signal intensity on T2-weighted images and the mean apparent diffusion coefficient value on ADC maps of the initial MRI studies were compared between peripheral-zone (PZ) cancer and the normal PZ based on pathologic maps of patients who had undergone radical prostatectomy. Results: The clinical NPV of mp-MRI was 89.6% for significant prostate cancer. Small cancers, prostatitis, and benign prostatic hypertrophy masking prostate cancer returned false-negative results. Quantitative analysis showed that there was no significant difference between PZ cancer and the normal PZ. Conclusion: The mp-MRI revealed a high clinical NPV and is a useful tool to rule out clinically significant prostate cancer before biopsy.

  11. Negative predictive value of multiparametric MRI for prostate cancer detection: Outcome of 5-year follow-up in men with negative findings on initial MRI studies

    International Nuclear Information System (INIS)

    Itatani, R.; Namimoto, T.; Atsuji, S.; Katahira, K.; Morishita, S.; Kitani, K.; Hamada, Y.; Kitaoka, M.; Nakaura, T.; Yamashita, Y.

    2014-01-01

    Highlights: • We assess the negative predictive value of multiparametric MRI for prostate cancer. • Patients with positive prostate biopsy findings were defined as false-negative. • Patients with negative initial prostate biopsy findings were followed up for 5 years. • The negative predictive value was 89.6% for significant prostate cancer. • MRI is a useful tool to rule out significant prostate cancer before biopsy. - Abstract: Objective: To assess the clinical negative predictive value (NPV) of multiparametric MRI (mp-MRI) for prostate cancer in a 5-year follow-up. Materials and methods: One hundred ninety-three men suspected of harboring prostate cancer with negative MRI findings were included. Patients with positive transrectal ultrasound (TRUS)-guided biopsy findings were defined as false-negative. Patients with negative initial TRUS-guided biopsy findings were followed up and only patients with negative findings by digital rectal examination, MRI, and repeat biopsy and no increase in PSA at 5-year follow-up were defined as “clinically negative”. The clinical NPV of mp-MRI was calculated. For quantitative analysis, mean signal intensity on T2-weighted images and the mean apparent diffusion coefficient value on ADC maps of the initial MRI studies were compared between peripheral-zone (PZ) cancer and the normal PZ based on pathologic maps of patients who had undergone radical prostatectomy. Results: The clinical NPV of mp-MRI was 89.6% for significant prostate cancer. Small cancers, prostatitis, and benign prostatic hypertrophy masking prostate cancer returned false-negative results. Quantitative analysis showed that there was no significant difference between PZ cancer and the normal PZ. Conclusion: The mp-MRI revealed a high clinical NPV and is a useful tool to rule out clinically significant prostate cancer before biopsy

  12. Cancer-related symptoms predict psychological wellbeing among prostate cancer survivors: results from the PiCTure study.

    Science.gov (United States)

    Sharp, Linda; O'Leary, Eamonn; Kinnear, Heather; Gavin, Anna; Drummond, Frances J

    2016-03-01

    Prostate cancer treatments are associated with a range of symptoms and physical side-effects. Cancer can also adversely impact on psychological wellbeing. Because many prostate cancer-related symptoms and side-effects are potentially modifiable, we investigated associations between symptoms and psychological wellbeing among prostate cancer survivors. Postal questionnaires were distributed to men diagnosed with prostate cancer 2-18 years previously identified through cancer registries. General and prostate cancer-specific symptoms were assessed using the EORTC QLQ-C30 and QLQ-PR25, with higher symptom scores indicating more/worse symptomatology. Psychological wellbeing was assessed by the DASS-21. Associations between symptoms and each outcome were investigated using multivariate logistic regression, controlling for socio-demographic and clinical factors. A total 3348 men participated (response rate = 54%). Seventeen percent (95%CI 15.2%-17.9%), 16% (95%CI 15.1%-17.8%) and 11% (95%CI 9.5%-11.8%) of survivors scored in the range for depression, anxiety and distress on the DASS scales, respectively. In multivariate models, risk of depression on the DASS scale was significantly higher in men with higher urinary and androgen deprivation therapy (ADT)-related symptoms, and higher scores for fatigue, insomnia and financial difficulties. Risk of anxiety on the DASS scale was higher in men with higher scores for urinary, bowel and ADT-related symptoms and fatigue, dyspnoea and financial difficulties. Risk of distress on the DASS scale was positively associated with urinary, bowel and ADT-related symptoms, fatigue, insomnia and financial difficulties. Cancer-related symptoms significantly predict psychological wellbeing among prostate cancer survivors. Greater use of interventions and medications and to alleviate symptoms might improve psychological wellbeing of prostate cancer survivors. Copyright © 2015 John Wiley & Sons, Ltd.

  13. Integrative Analysis of Gene Expression Data Including an Assessment of Pathway Enrichment for Predicting Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Pingzhao Hu

    2006-01-01

    biological pathways. In particular, we observed that by integrating information from the insulin signalling pathway into our prediction model, we achieved better prediction of prostate cancer. Conclusions: Our data integration methodology provides an efficient way to identify biologically sound and statistically significant pathways from gene expression data. The significant gene expression phenotypes identified in our study have the potential to characterize complex genetic alterations in prostate cancer.

  14. Urinary engrailed-2 (EN2) levels predict tumour volume in men undergoing radical prostatectomy for prostate cancer

    DEFF Research Database (Denmark)

    Pandha, Hardev; Sørensen, Karina Dalsgaard; Ørntoft, Torben Falck

    2012-01-01

    ELISA test and is not dependent on other parameters, even PSA, unlike all the other current biomarkers under evaluation. To date, no marker correlates with the amount of cancer present - the present study shows this positive correlation with EN2 in men undergoing prostatectomy. The potential utility...... in men who had undergone radical prostatectomy (RP) for prostate cancer. To date, prostate-specific antigen (PSA) levels have not reliably predicted prostate cancer volume. Reliable volume indicator biomarker(s) may aid management decisions, e.g. active treatment vs active surveillance. PATIENTS......: In all, 88 of the whole cohort of 125 men (70%) were positive for EN2 in their urine (>42.5 µg/L); 38/58 (65%) men where cancer volume data was available. There was no statistical relationship between urinary EN2 levels and serum PSA levels. PSA levels did not correlate with tumour stage, combined...

  15. [Prediction of life expectancy for prostate cancer patients based on the kinetic theory of aging of living systems].

    Science.gov (United States)

    Viktorov, A A; Zharinov, G M; Neklasova, N Ju; Morozova, E E

    2017-01-01

    The article presents a methodical approach for prediction of life expectancy for people diagnosed with prostate cancer based on the kinetic theory of aging of living systems. The life expectancy is calculated by solving the differential equation for the rate of aging for three different stage of life - «normal» life, life with prostate cancer and life after combination therapy for prostate cancer. The mathematical model of aging for each stage of life has its own parameters identified by the statistical analysis of healthcare data from the Zharinov's databank and Rosstat CDR NES databank. The core of the methodical approach is the statistical correlation between growth rate of the prostate specific antigen level (PSA-level) or the PSA doubling time (PSA DT) before therapy, and lifespan: the higher the PSA DT is, the greater lifespan. The patients were grouped under the «fast PSA DT» and «slow PSA DT» categories. The satisfactory matching between calculations and experiment is shown. The prediction error of group life expectancy is due to the completeness and reliability of the main data source. A detailed monitoring of the basic health indicators throughout the each person life in each analyzed group is required. The absence of this particular information makes it impossible to predict the individual life expectancy.

  16. A Novel Method for Predicting Late Genitourinary Toxicity After Prostate Radiation Therapy and the Need for Age-Based Risk-Adapted Dose Constraints

    International Nuclear Information System (INIS)

    Ahmed, Awad A.; Egleston, Brian; Alcantara, Pino; Li, Linna; Pollack, Alan; Horwitz, Eric M.; Buyyounouski, Mark K.

    2013-01-01

    Background: There are no well-established normal tissue sparing dose–volume histogram (DVH) criteria that limit the risk of urinary toxicity from prostate radiation therapy (RT). The aim of this study was to determine which criteria predict late toxicity among various DVH parameters when contouring the entire solid bladder and its contents versus the bladder wall. The area under the histogram curve (AUHC) was also analyzed. Methods and Materials: From 1993 to 2000, 503 men with prostate cancer received 3-dimensional conformal RT (median follow-up time, 71 months). The whole bladder and the bladder wall were contoured in all patients. The primary endpoint was grade ≥2 genitourinary (GU) toxicity occurring ≥3 months after completion of RT. Cox regressions of time to grade ≥2 toxicity were estimated separately for the entire bladder and bladder wall. Concordance probability estimates (CPE) assessed model discriminative ability. Before training the models, an external random test group of 100 men was set aside for testing. Separate analyses were performed based on the mean age (≤ 68 vs >68 years). Results: Age, pretreatment urinary symptoms, mean dose (entire bladder and bladder wall), and AUHC (entire bladder and bladder wall) were significant (P 68 years. Conclusion: The AUHC method based on bladder wall volumes was superior for predicting late GU toxicity. Age >68 years was associated with late grade ≥2 GU toxicity, which suggests that risk-adapted dose constraints based on age should be explored

  17. Antioxidant supplementation decreases the cell death rate in the prostatic stromal tissue of long-term castrated rats

    Directory of Open Access Journals (Sweden)

    Guilherme Fartes

    2012-06-01

    Full Text Available OBJECTIVE: The purpose of this study was to compare the effects of castration on cell death rate of the adult rat prostates and to evaluate the benefic action of alpha tocopherol supplementation to avoid apoptosis post-orchiectomy. MATERIAL AND METHODS: Thirty male Wistar rats weighing 250-300g were divided into three groups: group I - they were subjected to bilateral orchiectomy and sacrificed eight weeks after the procedure; group II - subjected to bilateral orchiectomy and alpha-tocopherol supplementation for four weeks preceding the procedure; and group III - subjected to bilateral orchiectomy and alpha-tocopherol supplementation for four weeks preceding the procedure and for eight weeks afterwards. At the end of the experiment, the prostatectomy was performed in all rats. The presence of oxidative stress was determined by assaying the blood level of 8-isoprostane and the occurrence of apoptosis was evaluated by identification of active caspase-3 through immunohistochemical analysis. RESULTS: The statistic analysis of active caspase-3 showed that in the long-term castrated group the detection was higher than in groups were the alpha-tocopherol was supplemented (p=0.007. Analysis of 8-isoprostane levels showed higher concentrations of reactive oxygen species in group I compared to other groups (p<0.05. Groups II and III presented active caspase-3 lower than in group I (p<0.05. CONCLUSION: Our exploratory analyses demonstrate a method to study the aging process and its influence on oxidative stress of prostatic tissue and cells death rate. Based on our results we can suggest that alpha tocopherol supplementation can decrease the apoptotic process as well as the oxidative stress levels induced by androgen deprivation of the prostate gland.

  18. Photoacoustic-based sO2 estimation through excised bovine prostate tissue with interstitial light delivery.

    Science.gov (United States)

    Mitcham, Trevor; Taghavi, Houra; Long, James; Wood, Cayla; Fuentes, David; Stefan, Wolfgang; Ward, John; Bouchard, Richard

    2017-09-01

    Photoacoustic (PA) imaging is capable of probing blood oxygen saturation (sO 2 ), which has been shown to correlate with tissue hypoxia, a promising cancer biomarker. However, wavelength-dependent local fluence changes can compromise sO 2 estimation accuracy in tissue. This work investigates using PA imaging with interstitial irradiation and local fluence correction to assess precision and accuracy of sO 2 estimation of blood samples through ex vivo bovine prostate tissue ranging from 14% to 100% sO 2 . Study results for bovine blood samples at distances up to 20 mm from the irradiation source show that local fluence correction improved average sO 2 estimation error from 16.8% to 3.2% and maintained an average precision of 2.3% when compared to matched CO-oximeter sO 2 measurements. This work demonstrates the potential for future clinical translation of using fluence-corrected and interstitially driven PA imaging to accurately and precisely assess sO 2 at depth in tissue with high resolution.

  19. Expression of Ku70 predicts results of radiotherapy in prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, Tomokazu; Someya, Masanori; Hori, Masakazu; Nakata, Kensei; Kitagawa, Mio; Tsuchiya, Takaaki; Sakata, Koh-ichi [Sapporo Medical University School of medicine, Department of Radiology, Chuo-ku, Sapporo, Hokkaido (Japan); Matsumoto, Yoshihisa [Research Laboratory for Nuclear Reactors, Tokyo Institute of Technology, Meguro-ku, Tokyo (Japan); Nojima, Masanori [The University of Tokyo, The Institute of Medical Science Hospital, Minatoku, Tokyo (Japan); Masumori, Naoya [Sapporo Medical University School of medicine, Department of Urology, Chuo-ku, Sapporo, Hokkaido (Japan); Hasegawa, Tadashi [Sapporo Medical University School of medicine, Department of Surgical Pathology, Chuo-ku, Sapporo, Hokkaido (Japan)

    2017-01-15

    Therapeutic strategy for prostate cancer is decided according to T stage, Gleason score, and prostate-specific antigen (PSA) level. These clinical factors are not accurate enough to predict individual risk of local failure of prostate cancer after radiotherapy. Parameters involved with radiosensitivity are required to improve the predictive capability for local relapse. We analyzed 58 patients with localized adenocarcinoma of the prostate between August 2007 and October 2010 treated with 76 Gy of intensity-modulated radiotherapy (IMRT) as a discovery cohort and 42 patients between March 2001 and May 2007 treated with three-dimensional conformal radiotherapy (3D-CRT) as a validation cohort. Immunohistochemical examination for proteins involved in nonhomologous end-joining was performed using biopsy specimens. Ku70 expression was not correlated with various clinical parameters, such as the Gleason score and D'amico risk classification, indicating that Ku70 expression was an independent prognostic factor. The predictive value for PSA relapse was markedly improved after the combination of Gleason score and Ku70 expression, as compared with Gleason score alone. In patients treated with radiotherapy and androgen deprivation therapy (ADT), no relapses were observed in patients with Gleason score ≤7 or low Ku70 expression. In contrast, patients with Gleason score ≥8 and high Ku70 expression had high PSA relapse rates. In the validation cohort, similar results were obtained. Treatment with 76 Gy and ADT can be effective for patients with Gleason score ≤7 or low Ku70 expression, but is not enough for patients with Gleason score ≥8 and high Ku70 expression and, thus, require other treatment approaches. (orig.) [German] Die Behandlung beim Prostatakarzinom ist abhaengig von T-Stadium, Gleason-Score und prostataspezifischem Antigen (PSA). Diese klinischen Faktoren sind jedoch zu ungenau, um das individuelle Lokalrezidivrisiko beim Prostatakarzinom nach

  20. Clinical performance of the Prostate Health Index (PHI) for the prediction of prostate cancer in obese men: data from the PROMEtheuS project, a multicentre European prospective study.

    Science.gov (United States)

    Abrate, Alberto; Lazzeri, Massimo; Lughezzani, Giovanni; Buffi, Nicolòmaria; Bini, Vittorio; Haese, Alexander; de la Taille, Alexandre; McNicholas, Thomas; Redorta, Joan Palou; Gadda, Giulio M; Lista, Giuliana; Kinzikeeva, Ella; Fossati, Nicola; Larcher, Alessandro; Dell'Oglio, Paolo; Mistretta, Francesco; Freschi, Massimo; Guazzoni, Giorgio

    2015-04-01

    To test serum prostate-specific antigen (PSA) isoform [-2]proPSA (p2PSA), p2PSA/free PSA (%p2PSA) and Prostate Health Index (PHI) accuracy in predicting prostate cancer in obese men and to test whether PHI is more accurate than PSA in predicting prostate cancer in obese patients. The analysis consisted of a nested case-control study from the pro-PSA Multicentric European Study (PROMEtheuS) project. The study is registered at http://www.controlled-trials.com/ISRCTN04707454. The primary outcome was to test sensitivity, specificity and accuracy (clinical validity) of serum p2PSA, %p2PSA and PHI, in determining prostate cancer at prostate biopsy in obese men [body mass index (BMI) ≥30 kg/m(2) ], compared with total PSA (tPSA), free PSA (fPSA) and fPSA/tPSA ratio (%fPSA). The number of avoidable prostate biopsies (clinical utility) was also assessed. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis. Of the 965 patients, 383 (39.7%) were normal weight (BMI PHI were significantly higher, and %fPSA significantly lower in patients with prostate cancer (P PHI significantly increased accuracy of the base multivariable model by 8.8% (P = 0.007). At a PHI threshold of 35.7, 46 (32.4%) biopsies could have been avoided. In obese patients, PHI is significantly more accurate than current tests in predicting prostate cancer. © 2014 The Authors. BJU International © 2014 BJU International.

  1. The application of three-dimensional contrast-enhanced ultrasound to measure volume of affected tissue after HIFU treatment for localized prostate cancer

    NARCIS (Netherlands)

    Sedelaar, J. P.; Aarnink, R. G.; van Leenders, G. J.; Beerlage, H. P.; Debruyne, F. M.; Wijkstra, H.; de la Rosette, J. J.

    2000-01-01

    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

  2. Daily online bony correction is required for prostate patients without fiducial markers or soft-tissue imaging.

    Science.gov (United States)

    Johnston, M L; Vial, P; Wiltshire, K L; Bell, L J; Blome, S; Kerestes, Z; Morgan, G W; O'Driscoll, D; Shakespeare, T P; Eade, T N

    2011-09-01

    To compare online position verification strategies with offline correction protocols for patients undergoing definitive prostate radiotherapy. We analysed 50 patients with implanted fiducial markers undergoing curative prostate radiation treatment, all of whom underwent daily kilovoltage imaging using an on-board imager. For each treatment, patients were set-up initially with skin tattoos and in-room lasers. Orthogonal on-board imager images were acquired and the couch shift to match both bony anatomy and the fiducial markers recorded. The set-up error using skin tattoos and offline bone correction was compared with online bone correction. The fiducial markers were used as the reference. Data from 1923 fractions were analysed. The systematic error was ≤1 mm for all protocols. The average random error was 2-3mm for online bony correction and 3-5mm for skin tattoos or offline-bone. Online-bone showed a significant improvement compared with offline-bone in the number of patients with >5mm set-up errors for >10% (P20% (Pmarkers or daily soft-tissue imaging. Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  3. Improving the prediction of pathologic outcomes in patients undergoing radical prostatectomy: the value of prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine.

    Science.gov (United States)

    Ferro, Matteo; Lucarelli, Giuseppe; Bruzzese, Dario; Perdonà, Sisto; Mazzarella, Claudia; Perruolo, Giuseppe; Marino, Ada; Cosimato, Vincenzo; Giorgio, Emilia; Tagliamonte, Virginia; Bottero, Danilo; De Cobelli, Ottavio; Terracciano, Daniela

    2015-02-01

    Several efforts have been made to find biomarkers that could help clinicians to preoperatively determine prostate cancer (PCa) pathological characteristics and choose the best therapeutic approach, avoiding over-treatment. On this effort, prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine have been presented as promising tools. We evaluated the ability of these biomarkers to predict the pathologic PCa characteristics within a prospectively collected contemporary cohort of patients who underwent radical prostatectomy (RP) for clinically localized PCa at a single high-volume Institution. The prognostic performance of PCA3, phi and sarcosine were evaluated in 78 patients undergoing RP for biopsy-proven PCa. Receiver operating characteristic (ROC) curve analyses tested the accuracy (area under the curve (AUC)) in predicting PCa pathological characteristics. Decision curve analyses (DCA) were used to assess the clinical benefit of the three biomarkers. We found that PCA3, phi and sarcosine levels were significantly higher in patients with tumor volume (TV)≥0.5 ml, pathologic Gleason sum (GS)≥7 and pT3 disease (all p-values≤0.01). ROC curve analysis showed that phi is an accurate predictor of high-stage (AUC 0.85 [0.77-0.93]), high-grade (AUC 0.83 [0.73-0.93]) and high-volume disease (AUC 0.94 [0.88-0.99]). Sarcosine showed a comparable AUC (0.85 [0.76-0.94]) only for T3 stage prediction, whereas PCA3 score showed lower AUCs, ranging from 0.74 (for GS) to 0.86 (for TV). PCA3, phi and sarcosine are predictors of PCa characteristics at final pathology. Successful clinical translation of these findings would reduce the frequency of surveillance biopsies and may enhance acceptance of active surveillance (AS). Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  4. Prostate biopsy

    Science.gov (United States)

    ... give the cells a grade called a Gleason score . This helps predict how fast the cancer will ... TRUS); Stereotactic transperineal prostate biopsy (STPB) Images Male reproductive anatomy References Babayan RK, Katz MH. Biopsy prophylaxis, ...

  5. Pre-Operative Prediction of Advanced Prostatic Cancer Using Clinical Decision Support Systems: Accuracy Comparison between Support Vector Machine and Artificial Neural Network

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Youn; Moon, Sung Kyoung; Hwang, Sung Il; Sung, Chang Kyu; Cho, Jeong Yeon; Kim, Seung Hyup; Lee, Hak Jong [Seoul National University College of Medicine, Seoul (Korea, Republic of); Jung, Dae Chul [National Cancer Center, Ilsan (Korea, Republic of); Lee, Ji Won [Kangwon National University College of Medicine, Chuncheon (Korea, Republic of)

    2011-10-15

    The purpose of the current study was to develop support vector machine (SVM) and artificial neural network (ANN) models for the pre-operative prediction of advanced prostate cancer by using the parameters acquired from transrectal ultrasound (TRUS)-guided prostate biopsies, and to compare the accuracies between the two models. Five hundred thirty-two consecutive patients who underwent prostate biopsies and prostatectomies for prostate cancer were divided into the training and test groups (n = 300 versus n 232). From the data in the training group, two clinical decision support systems (CDSSs-[SVM and ANN]) were constructed with input (age, prostate specific antigen level, digital rectal examination, and five biopsy parameters) and output data (the probability for advanced prostate cancer [> pT3a]). From the data of the test group, the accuracy of output data was evaluated. The areas under the receiver operating characteristic (ROC) curve (AUC) were calculated to summarize the overall performances, and a comparison of the ROC curves was performed (p < 0.05). The AUC of SVM and ANN is 0.805 and 0.719, respectively (p = 0.020), in the pre-operative prediction of advanced prostate cancer. Te performance of SVM is superior to ANN in the pre-operative prediction of advanced prostate cancer.

  6. Diffusion-weighted magnetic resonance imaging for prediction of insignificant prostate cancer in potential candidates for active surveillance

    International Nuclear Information System (INIS)

    Kim, Tae Heon; Jeong, Jae Yong; Lee, Sin Woo; Sung, Hyun Hwan; Jeon, Hwang Gyun; Jeong, Byong Chang; Seo, Seong Il; Lee, Hyun Moo; Choi, Han Yong; Jeon, Seong Soo; Kim, Chan Kyo; Park, Byung Kwan

    2015-01-01

    To investigate whether the apparent diffusion coefficient (ADC) from diffusion-weighted magnetic resonance imaging (DW-MRI) could help improve the prediction of insignificant prostate cancer in candidates for active surveillance (AS). Enrolled in this retrospective study were 287 AS candidates who underwent DW-MRI before radical prostatectomy. Patients were stratified into two groups; Group A consisted of patients with no visible tumour or a suspected tumour ADC value > 0.830 x 10 -3 mm 2 /sec and Group B consisted of patients with a suspected tumour ADC value < 0.830 x 10 -3 mm 2 /sec. We compared pathological outcomes in each group. Group A had 243 (84.7 %) patients and Group B had 44 (15.3 %) patients. The proportion of organ-confined Gleason ≤ 6 disease and insignificant prostate cancer was significantly higher in Group A than Group B (61.3 % vs. 38.6 %, p = 0.005 and 47.7 % vs. 25.0 %, p = 0.005, respectively). On multivariate analysis, a high ADC value was the independent predictor of organ-confined Gleason ≤ 6 disease and insignificant prostate cancer (odds ratio = 2.43, p = 0.011 and odds ratio = 2.74, p = 0.009, respectively). Tumour ADC values may be a useful marker for predicting insignificant prostate cancer in candidates for AS. (orig.)

  7. Percent free prostate-specific antigen is effective to predict prostate biopsy outcome in Chinese men with prostate-specific antigen between 10.1 and 20.0 ng ml−1

    Science.gov (United States)

    Chen, Rui; Zhou, Li-Qun; Cai, Xiao-Bing; Xie, Li-Ping; Huang, Yi-Ran; He, Da-Lin; Gao, Xu; Xu, Chuan-Liang; Ding, Qiang; Wei, Qiang; Yin, Chang-Jun; Ren, Shan-Cheng; Wang, Fu-Bo; Tian, Ye; Sun, Zhong-Quan; Fu, Qiang; Ma, Lu-Lin; Zheng, Jun-Hua; Ye, Zhang-Qun; Ye, Ding-Wei; Xu, Dan-Feng; Hou, Jian-Quan; Xu, Ke-Xin; Yuan, Jian-Lin; Gao, Xin; Liu, Chun-Xiao; Pan, Tie-Jun; Sun, Ying-Hao

    2015-01-01

    Percent free prostatic-specific antigen (%fPSA) has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0–10.0 ng ml−1, however, it remains controversial whether %fPSA is effective in PSA range of 10.1–20.0 ng ml−1 in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer (PCa) and high-grade PCa (HGPCa) was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA>4.0 ng ml−1 or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA (%fPSA + PSA) was determined by the area under the receivers operating characteristic curve (AUC). %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0–10.0 ng ml−1 and 10.1–20.0 ng ml−1, respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0–10.0 ng ml−1 and 10.1–20.0 ng ml−1. PMID:25926603

  8. Percent free prostate-specific antigen is effective to predict prostate biopsy outcome in Chinese men with prostate-specific antigen between 10.1 and 20.0 ng ml(-1).

    Science.gov (United States)

    Chen, Rui; Zhou, Li-Qun; Cai, Xiao-Bing; Xie, Li-Ping; Huang, Yi-Ran; He, Da-Lin; Gao, Xu; Xu, Chuan-Liang; Ding, Qiang; Wei, Qiang; Yin, Chang-Jun; Ren, Shan-Cheng; Wang, Fu-Bo; Tian, Ye; Sun, Zhong-Quan; Fu, Qiang; Ma, Lu-Lin; Zheng, Jun-Hua; Ye, Zhang-Qun; Ye, Ding-Wei; Xu, Dan-Feng; Hou, Jian-Quan; Xu, Ke-Xin; Yuan, Jian-Lin; Gao, Xin; Liu, Chun-Xiao; Pan, Tie-Jun; Sun, Ying-Hao

    2015-01-01

    Percent free prostatic-specific antigen (%fPSA) has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0-10.0 ng ml-1 , however, it remains controversial whether %fPSA is effective in PSA range of 10.1-20.0 ng ml-1 in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer (PCa) and high-grade PCa (HGPCa) was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA>4.0 ng ml-1 or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA (%fPSA + PSA) was determined by the area under the receivers operating characteristic curve (AUC). %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0-10.0 ng ml-1 and 10.1-20.0 ng ml-1 , respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0-10.0 ng ml-1 and 10.1-20.0 ng ml-1 .

  9. Low serum testosterone predicts upgrading and upstaging of prostate cancer after radical prostatectomy

    Directory of Open Access Journals (Sweden)

    Yuan Gao

    2016-01-01

    Full Text Available Often, pathological Gleason Score (GS and stage of prostate cancer (PCa were inconsistent with biopsy GS and clinical stage. However, there were no widely accepted methods predicting upgrading and upstaging PCa. In our study, we investigated the association between serum testosterone and upgrading or upstaging of PCa after radical prostatectomy (RP. We enrolled 167 patients with PCa with biopsy GS ≤6, clinical stage ≤T2c, and prostate-specific antigen (PSA <10 ng ml−1 from April 2009 to April 2015. Data including age, body mass index, preoperative PSA level, comorbidity, clinical presentation, and preoperative serum total testosterone level were collected. Upgrading occurred in 62 (37.1% patients, and upstaging occurred in 73 (43.7% patients. Preoperative testosterone was lower in the upgrading than nonupgrading group (3.72 vs 4.56, P< 0.01. Patients in the upstaging group had lower preoperative testosterone than those in the nonupstaging group (3.84 vs 4.57, P= 0.01. In multivariate logistic regression analysis, as both continuous and categorical variables, low serum testosterone was confirmed to be an independent predictor of pathological upgrading (P = 0.01 and P= 0.01 and upstaging (P = 0.01 and P = 0.02 after RP. We suggest that low serum testosterone (<3 ng ml−1 is associated with a high rate of upgrading and upstaging after RP. It is better for surgeons to ensure close monitoring of PSA levels and imaging examination when selecting non-RP treatment, to be cautious in proceeding with nerve-sparing surgery, and to be enthusiastic in performing extended lymph node dissection when selecting RP treatment for patients with low serum testosterone.

  10. Frequency of carcinoma of prostate in clinically benign prostatic hyperplasia and role of different screening tests

    International Nuclear Information System (INIS)

    Rasool, M.; Saeed, M.; Ali, S.; Saleem, M.S.; Saleem, M.S.

    2012-01-01

    Objectives: To assess the frequency of carcinoma in clinically benign prostatic hyperplasia and role. of digital rectal examination (DRE) and prostatic specific antigen (PSA) in assessment of these patients. Data source: Patients admitted to the Department of Urology and Renal Transplantation with lower urinary tract symptoms (LUTS) due to enlarged prostate. Design of study: Descriptive Study Place and Duration of Study: Department of Urology and Renal Transplantation, Quaid-e-Azam Medical College Bahawal Victoria Hospital, Bahawalpur, from January 2007 to December 2010. Patients and Methods: Patients presenting with lower urinary tract symptoms over the age of 50 years were evaluated on International Prostate Symptoms Score (IPSS), clinically examined and post-voiding residual urine determined on abdominal ultrasonography. The selection criteria were; Refractory retention of urine, Severe IPSS, absence of signs of malignancy on Digital Rectal Examination (DRE) and post-voiding residual urine more than 100 mI. Thus a total 300 patients were selected. Patient's blood sample was sent to laboratory to assess Prostate Specific Antigen (PSA) level pre-operatively. All these patients underwent either transurethral resection of prostate (TURP) or transvesical prostatectomy (TVP) and prostatic tissue was sent for histopathology. Results: In this study, 13.33% patients were found to have carcinoma of prostate in spite of being clinically benign prostates in all patients, irrespective of PSA range. The PSA value was found 4ngjml. In this study, 9.95% patients had carcinoma prostate in spite having normal PSA and benign prostate on DRE while with rising PSA levels and normal DRE, chances of malignancy detection increases (66.67% ). Conclusion: We conclude that although frequency is low the possibility of malignancy in clinically benign enlarged prostate should be borne in mind whenever subjecting the patient for screening, assessment and treatment. DRE alone is insufficient

  11. Analysis of the value of post-radiation prostate biopsy in predicting subsequent disease progression

    International Nuclear Information System (INIS)

    Benda, R.; Shamsa, F.; Meetze, K.; Bolton, S.; Littrup, P.; Grignon, D.; Washington, T.; Forman, J.D.

    1997-01-01

    Purpose: To analyze the value of Transrectal ultrasound(TRUS), Color flow doppler(CFD) and Prostate specific antigen(PSA) in identifying residual disease in the prostate status post external beam radiation therapy and to determine the value of this pathologic information in predicting subsequent disease progression. Materials and Methods: As part of four prospective protocols, 146 patients had scheduled TRUS guided prostate biopsies 6-25 months status post radiation therapy. The stage distribution was: 13% T1, 51% T2, and 36% T3/T4. Fifty six percent had neo-adjuvant hormones. Conformal photon or mixed neutron/photon irradiation was given to a median 2 Gy/fraction equivalent dose of 77 Gy(range 74 to 84 Gy). Following treatment, patients were assessed by digital rectal exam (DRE), PSA and TRUS guided biopsies at 6, 12 and/or 18 months. The ultrasound and CFD results were scored as normal, suspicious or abnormal. Sextant biopsies were obtained as well as ultrasound guided biopsies from any abnormal ultrasound or doppler area. The biopsies, all read by one pathologist (DG), were graded as negative, marked, moderate, minimal therapeutic effect or positive. The median followup post radiation therapy was 33.6 months and post biopsy was 25.3 months. Comparisons were done by Kappa index with corresponding 95% CI, chi square and Fisher's exact tests. Results: Twenty-eight patients had biopsies at both six and 12-18 months. Overall 35% of patients had all negative cores, 30% had at least one core showing a marked therapeutic effect, and 35% had at least one core showing moderate or minimal therapeutic effect or were positive. Although CFD correlated with a positive biopsy in 9% and a suspicious doppler identified cancer in 15% of cases, an abnormal TRUS identified cancer in 29.5% biopsies ((49(166))). However, a serum PSA >1.5ng/ml at the time of biopsy predicted 61% of positive biopsies ((23(38))). A negative biopsy was associated with low stage (≤T2c, p=0.001), low pre

  12. Prostate health index and prostate cancer gene 3 score but not percent-free Prostate Specific Antigen have a predictive role in differentiating histological prostatitis from PCa and other nonneoplastic lesions (BPH and HG-PIN) at repeat biopsy.

    Science.gov (United States)

    De Luca, Stefano; Passera, Roberto; Fiori, Cristian; Bollito, Enrico; Cappia, Susanna; Mario Scarpa, Roberto; Sottile, Antonino; Franco Randone, Donato; Porpiglia, Francesco

    2015-10-01

    To determine if prostate health index (PHI), prostate cancer antigen gene 3 (PCA3) score, and percentage of free prostate-specific antigen (%fPSA) may be used to differentiate asymptomatic acute and chronic prostatitis from prostate cancer (PCa), benign prostatic hyperplasia (BPH), and high-grade prostate intraepithelial neoplasia (HG-PIN) in patients with elevated PSA levels and negative findings on digital rectal examination at repeat biopsy (re-Bx). In this prospective study, 252 patients were enrolled, undergoing PHI, PCA3 score, and %fPSA assessments before re-Bx. We used 3 multivariate logistic regression models to test the PHI, PCA3 score, and %fPSA as risk factors for prostatitis vs. PCa, vs. BPH, and vs. HG-PIN. All the analyses were performed for the whole patient cohort and for the "gray zone" of PSA (4-10ng/ml) cohort (171 individuals). Of the 252 patients, 43 (17.1%) had diagnosis of PCa. The median PHI was significantly different between men with a negative biopsy and those with a positive biopsy (34.9 vs. 48.1, Pprostatitis and PCa was moderate, although it extended to a good range of threshold probabilities (40%-100%), whereas that from using %fPSA was negligible: this pattern was reported for the whole population as for the "gray zone" PSA cohort. In front of a good diagnostic performance of all the 3 biomarkers in distinguishing negative biopsy vs. positive biopsy, the clinical benefit of using the PCA3 score and PHI to estimate prostatitis vs. PCa was comparable. PHI was the only determinant for prostatitis vs. BPH, whereas no biomarkers could differentiate prostate inflammation from HG-PIN. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Magnetic resonance spectroscopic imaging of benign prostatic tissue: findings at 3.0 T compared to 1.5 T—initial experience☆

    Science.gov (United States)

    Chitkara, Munish; Westphalen, Antonio; Kurhanewicz, John; Qayyum, Aliya; Poder, Liina; Reed, Galen; Coakley, Fergus V.

    2013-01-01

    In a retrospective study of 71 voxels of benign peripheral zone tissue from 3 men who underwent endorectal magnetic resonance (MR) spectroscopic imaging of the prostate at both 1.5 and 3 T, 21 voxels that appeared more malignant at 3 T to either of two readers demonstrated significantly higher levels of choline and polyamines at 3 T compared to 1.5 T using a Wilcoxon ranked-sum test; awareness of this selective amplification of these metabolic signals at high field strength may help avoid overdiagnosis of prostate cancer. PMID:21724122

  14. Evaluation of PSA-age volume score in predicting prostate cancer in Chinese populationArticle Subject.

    Science.gov (United States)

    Wu, Yi-Shuo; Wu, Xiao-Bo; Zhang, Ning; Jiang, Guang-Liang; Yu, Yang; Tong, Shi-Jun; Jiang, Hao-Wen; Mao, Shan-Hua; Na, Rong; Ding, Qiang

    2018-02-06

    This study was performed to evaluate prostate-specific antigen-age volume (PSA-AV) scores in predicting prostate cancer (PCa) in a Chinese biopsy population. A total of 2355 men who underwent initial prostate biopsy from January 2006 to November 2015 in Huashan Hospital were recruited in the current study. The PSA-AV scores were calculated and assessed together with PSA and PSA density (PSAD) retrospectively. Among 2133 patients included in the analysis, 947 (44.4%) were diagnosed with PCa. The mean age, PSA, and positive rates of digital rectal examination result and transrectal ultrasound result were statistically higher in men diagnosed with PCa (all P PSA-AV were 0.864 and 0.851, respectively, in predicting PCa in the entire population, both performed better than PSA (AUC = 0.805; P PSA-AV was more obvious in subgroup with PSA ranging from 2.0 ng ml-1 to 20.0 ng ml-1. A PSA-AV score of 400 had a sensitivity and specificity of 93.7% and 40.0%, respectively. In conclusion, the PSA-AV score performed equally with PSAD and was better than PSA in predicting PCa. This indicated that PSA-AV score could be a useful tool for predicting PCa in Chinese population.

  15. Predicting objective function weights from patient anatomy in prostate IMRT treatment planning

    International Nuclear Information System (INIS)

    Lee, Taewoo; Hammad, Muhannad; Chan, Timothy C. Y.; Craig, Tim; Sharpe, Michael B.

    2013-01-01

    Purpose: Intensity-modulated radiation therapy (IMRT) treatment planning typically combines multiple criteria into a single objective function by taking a weighted sum. The authors propose a statistical model that predicts objective function weights from patient anatomy for prostate IMRT treatment planning. This study provides a proof of concept for geometry-driven weight determination. Methods: A previously developed inverse optimization method (IOM) was used to generate optimal objective function weights for 24 patients using their historical treatment plans (i.e., dose distributions). These IOM weights were around 1% for each of the femoral heads, while bladder and rectum weights varied greatly between patients. A regression model was developed to predict a patient's rectum weight using the ratio of the overlap volume of the rectum and bladder with the planning target volume at a 1 cm expansion as the independent variable. The femoral head weights were fixed to 1% each and the bladder weight was calculated as one minus the rectum and femoral head weights. The model was validated using leave-one-out cross validation. Objective values and dose distributions generated through inverse planning using the predicted weights were compared to those generated using the original IOM weights, as well as an average of the IOM weights across all patients. Results: The IOM weight vectors were on average six times closer to the predicted weight vectors than to the average weight vector, usingl 2 distance. Likewise, the bladder and rectum objective values achieved by the predicted weights were more similar to the objective values achieved by the IOM weights. The difference in objective value performance between the predicted and average weights was statistically significant according to a one-sided sign test. For all patients, the difference in rectum V54.3 Gy, rectum V70.0 Gy, bladder V54.3 Gy, and bladder V70.0 Gy values between the dose distributions generated by the

  16. Perineural Invasion Predicts Increased Recurrence, Metastasis, and Death From Prostate Cancer Following Treatment With Dose-Escalated Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Felix Y. [University of Michigan Medical Center, Ann Arbor, MI (United States); Ann Arbor Veteran Affairs Medical System, Ann Arbor, MI (United States); Qian Yushen; Stenmark, Matthew H.; Halverson, Schuyler; Blas, Kevin; Vance, Sean [University of Michigan Medical Center, Ann Arbor, MI (United States); Sandler, Howard M. [Cedars Sinai Medical System, Los Angeles, CA (United States); Hamstra, Daniel A., E-mail: dhamm@med.umich.edu [University of Michigan Medical Center, Ann Arbor, MI (United States)

    2011-11-15

    Purpose: To assess the prognostic value of perineural invasion (PNI) for patients treated with dose-escalated external-beam radiation therapy for prostate cancer. Methods and Materials: Outcomes were analyzed for 651 men treated for prostate cancer with EBRT to a minimum dose {>=}75 Gy. We assessed the impact of PNI as well as pretreatment and treatment-related factors on freedom from biochemical failure (FFBF), freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival. Results: PNI was present in 34% of specimens at biopsy and was significantly associated with higher Gleason score (GS), T stage, and prostate-specific antigen level. On univariate and multivariate analysis, the presence of PNI was associated with worse FFBF (hazard ratio = 1.7, p <0.006), FFM (hazard ratio = 1.8, p <0.03), and CSS (HR = 1.4, p <0.05) compared with absence of PNI; there was no difference in overall survival. Seven-year rates of FFBF, FFM, and CCS were 64% vs. 80%, 84% vs. 92%, and 91% vs. 95% for those patients with and without PNI, respectively. On recursive partitioning analysis, PNI predicted for worse FFM and CSS in patients with GS 8-10, with FFM of 67% vs. 89% (p <0.02), and CSS of 69% vs. 91%, (p <0.04) at 7 years for those with and without PNI, respectively. Conclusions: The presence of PNI in the prostate biopsy predicts worse clinical outcome for patients treated with dose-escalated external-beam radiation therapy. Particularly in patients with GS 8-10 disease, the presence of PNI suggests an increased risk of metastasis and prostate cancer death.

  17. Perineural Invasion Predicts Increased Recurrence, Metastasis, and Death From Prostate Cancer Following Treatment With Dose-Escalated Radiation Therapy

    International Nuclear Information System (INIS)

    Feng, Felix Y.; Qian Yushen; Stenmark, Matthew H.; Halverson, Schuyler; Blas, Kevin; Vance, Sean; Sandler, Howard M.; Hamstra, Daniel A.

    2011-01-01

    Purpose: To assess the prognostic value of perineural invasion (PNI) for patients treated with dose-escalated external-beam radiation therapy for prostate cancer. Methods and Materials: Outcomes were analyzed for 651 men treated for prostate cancer with EBRT to a minimum dose ≥75 Gy. We assessed the impact of PNI as well as pretreatment and treatment-related factors on freedom from biochemical failure (FFBF), freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival. Results: PNI was present in 34% of specimens at biopsy and was significantly associated with higher Gleason score (GS), T stage, and prostate-specific antigen level. On univariate and multivariate analysis, the presence of PNI was associated with worse FFBF (hazard ratio = 1.7, p <0.006), FFM (hazard ratio = 1.8, p <0.03), and CSS (HR = 1.4, p <0.05) compared with absence of PNI; there was no difference in overall survival. Seven-year rates of FFBF, FFM, and CCS were 64% vs. 80%, 84% vs. 92%, and 91% vs. 95% for those patients with and without PNI, respectively. On recursive partitioning analysis, PNI predicted for worse FFM and CSS in patients with GS 8–10, with FFM of 67% vs. 89% (p <0.02), and CSS of 69% vs. 91%, (p <0.04) at 7 years for those with and without PNI, respectively. Conclusions: The presence of PNI in the prostate biopsy predicts worse clinical outcome for patients treated with dose-escalated external-beam radiation therapy. Particularly in patients with GS 8–10 disease, the presence of PNI suggests an increased risk of metastasis and prostate cancer death.

  18. Androgen Receptor Variant AR-V9 Is Coexpressed with AR-V7 in Prostate Cancer Metastases and Predicts Abiraterone Resistance.

    Science.gov (United States)

    Kohli, Manish; Ho, Yeung; Hillman, David W; Van Etten, Jamie L; Henzler, Christine; Yang, Rendong; Sperger, Jamie M; Li, Yingming; Tseng, Elizabeth; Hon, Ting; Clark, Tyson; Tan, Winston; Carlson, Rachel E; Wang, Liguo; Sicotte, Hugues; Thai, Ho; Jimenez, Rafael; Huang, Haojie; Vedell, Peter T; Eckloff, Bruce W; Quevedo, Jorge F; Pitot, Henry C; Costello, Brian A; Jen, Jin; Wieben, Eric D; Silverstein, Kevin A T; Lang, Joshua M; Wang, Liewei; Dehm, Scott M

    2017-08-15

    Purpose: Androgen receptor (AR) variant AR-V7 is a ligand-independent transcription factor that promotes prostate cancer resistance to AR-targeted therapies. Accordingly, efforts are under way to develop strategies for monitoring and inhibiting AR-V7 in castration-resistant prostate cancer (CRPC). The purpose of this study was to understand whether other AR variants may be coexpressed with AR-V7 and promote resistance to AR-targeted therapies. Experimental Design: We utilized complementary short- and long-read sequencing of intact AR mRNA isoforms to characterize AR expression in CRPC models. Coexpression of AR-V7 and AR-V9 mRNA in CRPC metastases and circulating tumor cells was assessed by RNA-seq and RT-PCR, respectively. Expression of AR-V9 protein in CRPC models was evaluated with polyclonal antisera. Multivariate analysis was performed to test whether AR variant mRNA expression in metastatic tissues was associated with a 12-week progression-free survival endpoint in a prospective clinical trial of 78 CRPC-stage patients initiating therapy with the androgen synthesis inhibitor, abiraterone acetate. Results: AR-V9 was frequently coexpressed with AR-V7. Both AR variant species were found to share a common 3' terminal cryptic exon, which rendered AR-V9 susceptible to experimental manipulations that were previously thought to target AR-V7 uniquely. AR-V9 promoted ligand-independent growth of prostate cancer cells. High AR-V9 mRNA expression in CRPC metastases was predictive of primary resistance to abiraterone acetate (HR = 4.0; 95% confidence interval, 1.31-12.2; P = 0.02). Conclusions: AR-V9 may be an important component of therapeutic resistance in CRPC. Clin Cancer Res; 23(16); 4704-15. ©2017 AACR . ©2017 American Association for Cancer Research.

  19. Tissue ablation after 120W greenlight laser vaporization and bipolar plasma vaporization of the prostate: a comparison using transrectal three-dimensional ultrasound volumetry

    Science.gov (United States)

    Kranzbühler, Benedikt; Gross, Oliver; Fankhauser, Christian D.; Hefermehl, Lukas J.; Poyet, Cédric; Largo, Remo; Müntener, Michael; Seifert, Hans-Helge; Zimmermann, Matthias; Sulser, Tullio; Müller, Alexander; Hermanns, Thomas

    2012-02-01

    Introduction and objectives: Greenlight laser vaporization (LV) of the prostate is characterized by simultaneous vaporization and coagulation of prostatic tissue resulting in tissue ablation together with excellent hemostasis during the procedure. It has been reported that bipolar plasma vaporization (BPV) of the prostate might be an alternative for LV. So far, it has not been shown that BPV is as effective as LV in terms of tissue ablation or hemostasis. We performed transrectal three-dimensional ultrasound investigations to compare the efficiency of tissue ablation between LV and BPV. Methods: Between 11.2009 and 5.2011, 50 patients underwent pure BPV in our institution. These patients were matched with regard to the pre-operative prostate volume to 50 LV patients from our existing 3D-volumetry-database. Transrectal 3D ultrasound and planimetric volumetry of the prostate were performed pre-operatively, after catheter removal, 6 weeks and 6 months. Results: Median pre-operative prostate volume was not significantly different between the two groups (45.3ml vs. 45.4ml; p=1.0). After catheter removal, median absolute volume reduction (BPV 12.4ml, LV 6.55ml) as well as relative volume reduction (27.8% vs. 16.4%) were significantly higher in the BPV group (p<0.001). After six weeks (42.9% vs. 33.3%) and six months (47.2% vs. 39.7%), relative volume reduction remained significantly higher in the BPV group (p<0.001). Absolute volume reduction was non-significantly higher in the BPV group after six weeks (18.4ml, 13.8ml; p=0.051) and six months (20.8ml, 18ml; p=0.3). Clinical outcome parameters improved significantly in both groups without relevant differences between the groups. Conclusions: Both vaporization techniques result in efficient tissue ablation with initial prostatic swelling. BPV seems to be superior due to a higher relative volume reduction. This difference had no clinical impact after a follow-up of 6M.

  20. Significance of prostatic weight in prostatism

    DEFF Research Database (Denmark)

    Jensen, K M; Bruskewitz, R C; Iversen, P

    1983-01-01

    In addition to routine evaluation, 68 patients with prostatism underwent blinded urodynamic testing prior to transurethral prostatectomy and were reexamined symptomatologically and urodynamically at 3 and 12 months after surgery to determine if prostatic weight could predict postoperative outcome....... Resected prostatic weight correlated with estimated weight at cystoscopy and with obstructive symptoms, but not with urodynamic variables of infravesical obstruction. Patients with small prostates improved symptomatologically to the same degree as patients with larger glands, although they did not improve...... to the same degree urodynamically. Prostatic weight, therefore, could not be used to predict the outcome of transurethral surgery....

  1. Prediction of prostate cancer extracapsular extension with high spatial resolution dynamic contrast-enhanced 3-T MRI

    International Nuclear Information System (INIS)

    Bloch, B.N.; Genega, Elizabeth M.; Costa, Daniel N.; Pedrosa, Ivan; Rofsky, Neil M.; Smith, Martin P.; Kressel, Herbert Y.; Ngo, Long; Sanda, Martin G.; DeWolf, William C.

    2012-01-01

    To assess the value of dynamic contrast-enhanced (DCE) combined with T2-weighted (T2W) endorectal coil (ERC) magnetic resonance imaging (MRI) at 3 T for determining extracapsular extension (ECE) of prostate cancer. In this IRB-approved study, ERC 3-T MRI of the prostate was performed in 108 patients before radical prostatectomy. T2W fast spin-echo and DCE 3D gradient echo images were acquired. The interpretations of readers with varied experience were analysed. MRI-based staging results were compared with radical prostatectomy histology. Descriptive statistics were generated for prediction of ECE and staging accuracies were determined by the area under the receiver-operating characteristic curve. The overall sensitivity, specificity, positive predictive value and negative predictive value for ECE were 75 %, 92 %, 79 % and 91 %, respectively. Diagnostic accuracy for staging was 86 %, 80 % and 91 % for all readers, experienced and less experienced readers, respectively. ERC 3-T MRI of the prostate combining DCE and T2W imaging is an accurate pretherapeutic staging tool for assessment of ECE in clinical practice across varying levels of reader experience. (orig.)

  2. A new plan-scoring method using normal tissue complication probability for personalized treatment plan decisions in prostate cancer

    Science.gov (United States)

    Kim, Kwang Hyeon; Lee, Suk; Shim, Jang Bo; Yang, Dae Sik; Yoon, Won Sup; Park, Young Je; Kim, Chul Yong; Cao, Yuan Jie; Chang, Kyung Hwan

    2018-01-01

    The aim of this study was to derive a new plan-scoring index using normal tissue complication probabilities to verify different plans in the selection of personalized treatment. Plans for 12 patients treated with tomotherapy were used to compare scoring for ranking. Dosimetric and biological indexes were analyzed for the plans for a clearly distinguishable group ( n = 7) and a similar group ( n = 12), using treatment plan verification software that we developed. The quality factor ( QF) of our support software for treatment decisions was consistent with the final treatment plan for the clearly distinguishable group (average QF = 1.202, 100% match rate, n = 7) and the similar group (average QF = 1.058, 33% match rate, n = 12). Therefore, we propose a normal tissue complication probability (NTCP) based on the plan scoring index for verification of different plans for personalized treatment-plan selection. Scoring using the new QF showed a 100% match rate (average NTCP QF = 1.0420). The NTCP-based new QF scoring method was adequate for obtaining biological verification quality and organ risk saving using the treatment-planning decision-support software we developed for prostate cancer.

  3. MRI findings of radiation-induced changes in the urethra and periurethral tissues after treatment for prostate cancer

    International Nuclear Information System (INIS)

    Marigliano, Chiara; Donati, Olivio F.; Vargas, Hebert Alberto; Akin, Oguz; Goldman, Debra A.; Eastham, James A.; Zelefsky, Michael J.; Hricak, Hedvig

    2013-01-01

    Purpose: To assess radiotherapy (RT)-induced changes in the urethra and periurethral tissues after treatment for prostate cancer (PCa). Methods and materials: This retrospective study included 108 men (median age, 64 years; range, 43–87 years) who received external-beam radiotherapy (EBRT) and/or brachytherapy for PCa and underwent endorectal-coil MRI of the prostate within 180 days before RT and a median of 20 months (range, 2–62 months) after RT. On all MRIs, two readers independently measured the urethral length (UL) and graded the margin definition (MD) of the urethral wall and the signal intensities (SIs) of the urethral wall and pelvic muscles on 4-point scales. Results: The mean urethral length decreased significantly from pre- to post-RT MRI (from 15.2 to 12.6 mm and from 14.4 to 12.9 mm for readers 1 and 2, respectively; both p-values <0.0001). Brachytherapy resulted in greater urethral shortening than EBRT. After RT, SI in the urethral wall increased in 57% (62/108) and 35% (38/108) of patients (readers 1 and 2, respectively). The frequency and magnitude of SI increase in pelvic muscles depended on muscle location. In the obturator internus muscle, SI increased more often after EBRT than after brachytherapy, while in the periurethral levator ani muscle SI increased more often after brachytherapy than after EBRT. Conclusion: After RT for PCa, MRI shows urethral shortening and increased SI of the urethral wall and pelvic muscles in substantial percentages of patients

  4. MRI findings of radiation-induced changes in the urethra and periurethral tissues after treatment for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Marigliano, Chiara [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Department of Radiology, University “Sapienza”, Rome (Italy); Donati, Olivio F., E-mail: olivio.donati@usz.ch [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Department of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich (Switzerland); Vargas, Hebert Alberto; Akin, Oguz; Goldman, Debra A. [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Eastham, James A. [Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Zelefsky, Michael J. [Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Hricak, Hedvig, E-mail: hricakh@mskcc.org [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2013-12-01

    Purpose: To assess radiotherapy (RT)-induced changes in the urethra and periurethral tissues after treatment for prostate cancer (PCa). Methods and materials: This retrospective study included 108 men (median age, 64 years; range, 43–87 years) who received external-beam radiotherapy (EBRT) and/or brachytherapy for PCa and underwent endorectal-coil MRI of the prostate within 180 days before RT and a median of 20 months (range, 2–62 months) after RT. On all MRIs, two readers independently measured the urethral length (UL) and graded the margin definition (MD) of the urethral wall and the signal intensities (SIs) of the urethral wall and pelvic muscles on 4-point scales. Results: The mean urethral length decreased significantly from pre- to post-RT MRI (from 15.2 to 12.6 mm and from 14.4 to 12.9 mm for readers 1 and 2, respectively; both p-values <0.0001). Brachytherapy resulted in greater urethral shortening than EBRT. After RT, SI in the urethral wall increased in 57% (62/108) and 35% (38/108) of patients (readers 1 and 2, respectively). The frequency and magnitude of SI increase in pelvic muscles depended on muscle location. In the obturator internus muscle, SI increased more often after EBRT than after brachytherapy, while in the periurethral levator ani muscle SI increased more often after brachytherapy than after EBRT. Conclusion: After RT for PCa, MRI shows urethral shortening and increased SI of the urethral wall and pelvic muscles in substantial percentages of patients.

  5. Non-Fourier based thermal-mechanical tissue damage prediction for thermal ablation.

    Science.gov (United States)

    Li, Xin; Zhong, Yongmin; Smith, Julian; Gu, Chengfan

    2017-01-02

    Prediction of tissue damage under thermal loads plays important role for thermal ablation planning. A new methodology is presented in this paper by combing non-Fourier bio-heat transfer, constitutive elastic mechanics as well as non-rigid motion of dynamics to predict and analyze thermal distribution, thermal-induced mechanical deformation and thermal-mechanical damage of soft tissues under thermal loads. Simulations and comparison analysis demonstrate that the proposed methodology based on the non-Fourier bio-heat transfer can account for the thermal-induced mechanical behaviors of soft tissues and predict tissue thermal damage more accurately than classical Fourier bio-heat transfer based model.

  6. Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores.

    Science.gov (United States)

    Lecarpentier, Julie; Silvestri, Valentina; Kuchenbaecker, Karoline B; Barrowdale, Daniel; Dennis, Joe; McGuffog, Lesley; Soucy, Penny; Leslie, Goska; Rizzolo, Piera; Navazio, Anna Sara; Valentini, Virginia; Zelli, Veronica; Lee, Andrew; Amin Al Olama, Ali; Tyrer, Jonathan P; Southey, Melissa; John, Esther M; Conner, Thomas A; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Steele, Linda; Ding, Yuan Chun; Neuhausen, Susan L; Hansen, Thomas V O; Osorio, Ana; Weitzel, Jeffrey N; Toss, Angela; Medici, Veronica; Cortesi, Laura; Zanna, Ines; Palli, Domenico; Radice, Paolo; Manoukian, Siranoush; Peissel, Bernard; Azzollini, Jacopo; Viel, Alessandra; Cini, Giulia; Damante, Giuseppe; Tommasi, Stefania; Peterlongo, Paolo; Fostira, Florentia; Hamann, Ute; Evans, D Gareth; Henderson, Alex; Brewer, Carole; Eccles, Diana; Cook, Jackie; Ong, Kai-Ren; Walker, Lisa; Side, Lucy E; Porteous, Mary E; Davidson, Rosemarie; Hodgson, Shirley; Frost, Debra; Adlard, Julian; Izatt, Louise; Eeles, Ros; Ellis, Steve; Tischkowitz, Marc; Godwin, Andrew K; Meindl, Alfons; Gehrig, Andrea; Dworniczak, Bernd; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Hahnen, Eric; Hauke, Jan; Rhiem, Kerstin; Kast, Karin; Arnold, Norbert; Ditsch, Nina; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Wand, Dorothea; Lasset, Christine; Stoppa-Lyonnet, Dominique; Belotti, Muriel; Damiola, Francesca; Barjhoux, Laure; Mazoyer, Sylvie; Van Heetvelde, Mattias; Poppe, Bruce; De Leeneer, Kim; Claes, Kathleen B M; de la Hoya, Miguel; Garcia-Barberan, Vanesa; Caldes, Trinidad; Perez Segura, Pedro; Kiiski, Johanna I; Aittomäki, Kristiina; Khan, Sofia; Nevanlinna, Heli; van Asperen, Christi J; Vaszko, Tibor; Kasler, Miklos; Olah, Edith; Balmaña, Judith; Gutiérrez-Enríquez, Sara; Diez, Orland; Teulé, Alex; Izquierdo, Angel; Darder, Esther; Brunet, Joan; Del Valle, Jesús; Feliubadalo, Lidia; Pujana, Miquel Angel; Lazaro, Conxi; Arason, Adalgeir; Agnarsson, Bjarni A; Johannsson, Oskar Th; Barkardottir, Rosa B; Alducci, Elisa; Tognazzo, Silvia; Montagna, Marco; Teixeira, Manuel R; Pinto, Pedro; Spurdle, Amanda B; Holland, Helene; Lee, Jong Won; Lee, Min Hyuk; Lee, Jihyoun; Kim, Sung-Won; Kang, Eunyoung; Kim, Zisun; Sharma, Priyanka; Rebbeck, Timothy R; Vijai, Joseph; Robson, Mark; Lincoln, Anne; Musinsky, Jacob; Gaddam, Pragna; Tan, Yen Y; Berger, Andreas; Singer, Christian F; Loud, Jennifer T; Greene, Mark H; Mulligan, Anna Marie; Glendon, Gord; Andrulis, Irene L; Toland, Amanda Ewart; Senter, Leigha; Bojesen, Anders; Nielsen, Henriette Roed; Skytte, Anne-Bine; Sunde, Lone; Jensen, Uffe Birk; Pedersen, Inge Sokilde; Krogh, Lotte; Kruse, Torben A; Caligo, Maria A; Yoon, Sook-Yee; Teo, Soo-Hwang; von Wachenfeldt, Anna; Huo, Dezheng; Nielsen, Sarah M; Olopade, Olufunmilayo I; Nathanson, Katherine L; Domchek, Susan M; Lorenchick, Christa; Jankowitz, Rachel C; Campbell, Ian; James, Paul; Mitchell, Gillian; Orr, Nick; Park, Sue Kyung; Thomassen, Mads; Offit, Kenneth; Couch, Fergus J; Simard, Jacques; Easton, Douglas F; Chenevix-Trench, Georgia; Schmutzler, Rita K; Antoniou, Antonis C; Ottini, Laura

    2017-07-10

    Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated-for the first time to our knowledge-associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/ 2 mutations and implications for cancer risk prediction. Materials and Methods We genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. Results In male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; P = 8.6 × 10 -6 ). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; P = 3.2 × 10 -9 ). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of BRCA1 mutations and from 19% to 61% for carriers of BRCA2 mutations, respectively. Conclusion PRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.

  7. The establishment and evaluation of a new model for the prediction of prostate cancer

    OpenAIRE

    Wang, Qi; Li, Yan-Feng; Jiang, Jun; Zhang, Yong; Liu, Xu-Dong; Li, Ke

    2017-01-01

    Abstract To develop a new prostate cancer predictor (PCP) model using the combination of total prostate-specific antigen (tPSA), free PSA (fPSA), and complexed PSA (cPSA). The diagnoses of all the included patients were confirmed pathologically in Daping Hospital between December 1, 2011 and December 1, 2014. There were 54 PCa cases and 579 benign prostatic hyperplasia (BPH) cases with tPSA levels of 2 to 10?ng/mL, and 48 PCa cases and 147 BPH cases with tPSA levels of 10 to 20?ng/mL. Logisti...

  8. Importance of prostate-specific antigen (PSA as a predictive factor for concordance between the Gleason scores of prostate biopsies and RADICAL prostatectomy specimens

    Directory of Open Access Journals (Sweden)

    Nelson Gianni de Lima

    2013-06-01

    Full Text Available OBJECTIVE: To evaluate the concordance between the Gleason scores of prostate biopsies and radical prostatectomy specimens, thereby highlighting the importance of the prostate-specific antigen (PSA level as a predictive factor of concordance. METHODS: We retrospectively analyzed 253 radical prostatectomy cases performed between 2006 and 2011. The patients were divided into 4 groups for the data analysis and dichotomized according to the preoperative PSA, <10 ng/mL and ≥10 ng/mL. A p-score <0.05 was considered significant. RESULTS: The average patient age was 63.3±7.8 years. The median PSA level was 9.3±4.9 ng/mL. The overall concordance between the Gleason scores was 52%. Patients presented preoperative PSA levels <10 ng/mL in 153 of 235 cases (65% and ≥10 ng/mL in 82 of 235 cases (35%. The Gleason scores were identical in 86 of 153 cases (56% in the <10 ng/mL group and 36 of 82 (44% cases in the ≥10 ng/mL group (p = 0.017. The biopsy underestimated the Gleason score in 45 (30% patients in the <10 ng/mL group and 38 (46% patients in the ≥10 ng/mL (p = 0.243. Specifically, the patients with Gleason 3 + 3 scores according to the biopsies demonstrated global concordance in 56 of 110 cases (51%. In this group, the patients with preoperative PSA levels <10 ng/dL had higher concordance than those with preoperative PSA levels ≥10 ng/dL (61% x 23%, p = 0.023, which resulted in 77% upgrading after surgery in those patients with PSA levels ≥10 ng/dl. CONCLUSION: The Gleason scores of needle prostate biopsies and those of the surgical specimens were concordant in approximately half of the global sample. The preoperative PSA level was a strong predictor of discrepancy and might improve the identification of those patients who tended to be upgraded after surgery, particularly in patients with Gleason scores of 3 + 3 in the prostate biopsy and preoperative PSA levels ≥10 ng/mL.

  9. Posttreatment Prostate-Specific Antigen 6 Months After Radiation With Androgen Deprivation Therapy Predicts for Distant Metastasis–Free Survival and Prostate Cancer–Specific Mortality

    Energy Technology Data Exchange (ETDEWEB)

    Naik, Mihir, E-mail: naikm@ccf.org [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Reddy, Chandana A.; Stephans, Kevin L.; Ciezki, Jay P. [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Garcia, Jorge; Grivas, Petros [Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Stephenson, Andrew J.; Klein, Eric A. [Department of Urology, Glickman Urology and Kidney Institute, Cleveland Clinic, Cleveland, Ohio (United States); Tendulkar, Rahul D. [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States)

    2016-11-01

    Objectives/Background: To determine whether a 6-month posttreatment prostate-specific antigen (PSA) value in patients with prostate cancer (PCa) treated with concurrent androgen deprivation therapy (ADT) and external beam radiation therapy (EBRT) serves as an early predictor for biochemical relapse free survival (bRFS), distant metastasis–free survival (DMFS), and prostate cancer–specific mortality (PCSM). Methods: A retrospective review of intermediate-risk and high-risk PCa patients treated with EBRT and concurrent ADT at a single institution between 1996 and 2012. All patients received high-dose radiation with either 78 Gy in 39 fractions or 70 Gy in 28 fractions. Kaplan-Meier analysis was used to estimate bRFS and DMFS, and cumulative incidence was used to estimate PCSM. Results: 532 patients were identified. The median follow-up time was 7.5 years (range, 1-16.25 years). The median initial PSA (iPSA) was 13.0 ng/mL (range, 0.37-255 ng/mL), and the median duration of ADT was 6 months (range, 1-78 months). The median PSA 6 months after EBRT was 0.1 ng/mL (range, 0-19 ng/mL), and 310 patients (58.3%) had a 6-month PSA ≤0.1 ng/mL. Multivariable analysis (MVA) demonstrated that a 6-month post-EBRT PSA of >0.1 ng/mL was an independent predictor of worse bRFS (hazard ratio [HR] = 2.518; P<.0001), DMFS (HR=3.743; P<.0001), and PCSM (HR=5.435; P<.0001). On MVA, a Gleason score of 8 to 10 also correlated with worse DMFS and PCSM (P<.05). The duration of ADT (1-6 vs >6 months) was not predictive of any clinical endpoint. Conclusions: A 6-month posttreatment PSA >0.1 ng/mL in intermediate-risk and high-risk PCa patients treated with concurrent high-dose EBRT and ADT is associated with worse bRFS, DMFS, and PCSM. The duration of ADT was not predictive of any clinical endpoint. A 6-month PSA after definitive EBRT and ADT helps identify patients at higher risk of disease progression and may serve as a predictive tool to select patients for early

  10. Predictive risk factors of postoperative urinary incontinence following holmium laser enucleation of the prostate during the initial learning period

    Directory of Open Access Journals (Sweden)

    Shuichiro Kobayashi

    Full Text Available ABSTRACT Purpose: To determine the predictive factors for postoperative urinary incontinence (UI following holmium laser enucleation of the prostate (HoLEP during the initial learning period. Patients and Methods: We evaluated 127 patients with benign prostatic hyperplasia who underwent HoLEP between January 2011 and December 2013. We recorded clinical variables, including blood loss, serum prostate-specific antigen levels, and the presence or absence of UI. Blood loss was estimated as a decline in postoperative hemoglobin levels. The predictive factors for postoperative UI were determined using a multivariable logistic regression analysis. Results: Postoperative UI occurred in 31 patients (24.4%, but it cured in 29 patients (93.5% after a mean duration of 12 weeks. Enucleation time >100 min (p=0.043 and blood loss >2.5g/dL (p=0.032 were identified as significant and independent risk factors for postoperative UI. Conclusions: Longer enucleation time and increased blood loss were independent predictors of postoperative UI in patients who underwent HoLEP during the initial learning period. Surgeons in training should take care to perform speedy enucleation maneuver with hemostasis.

  11. Strengths and weaknesses of EST-based prediction of tissue-specific alternative splicing

    Directory of Open Access Journals (Sweden)

    Vingron Martin

    2004-09-01

    Full Text Available Abstract Background Alternative splicing contributes significantly to the complexity of the human transcriptome and proteome. Computational prediction of alternative splice isoforms are usually based on EST sequences that also allow to approximate the expression pattern of the related transcripts. However, the limited number of tissues represented in the EST data as well as the different cDNA construction protocols may influence the predictive capacity of ESTs to unravel tissue-specifically expressed transcripts. Methods We predict tissue and tumor specific splice isoforms based on the genomic mapping (SpliceNest of the EST consensus sequences and library annotation provided in the GeneNest database. We further ascertain the potentially rare tissue specific transcripts as the ones represented only by ESTs derived from normalized libraries. A subset of the predicted tissue and tumor specific isoforms are then validated via RT-PCR experiments over a spectrum of 40 tissue types. Results Our strategy revealed 427 genes with at least one tissue specific transcript as well as 1120 genes showing tumor specific isoforms. While our experimental evaluation of computationally predicted tissue-specific isoforms revealed a high success rate in confirming the expression of these isoforms in the respective tissue, the strategy frequently failed to detect the expected restricted expression pattern. The analysis of putative lowly expressed transcripts using normalized cDNA libraries suggests that our ability to detect tissue-specific isoforms strongly depends on the expression level of the respective transcript as well as on the sensitivity of the experimental methods. Especially splice isoforms predicted to be disease-specific tend to represent transcripts that are expressed in a set of healthy tissues rather than novel isoforms. Conclusions We propose to combine the computational prediction of alternative splice isoforms with experimental validation for

  12. Genome-wide prediction and analysis of human tissue-selective genes using microarray expression data

    Directory of Open Access Journals (Sweden)

    Teng Shaolei

    2013-01-01

    Full Text Available Abstract Background Understanding how genes are expressed specifically in particular tissues is a fundamental question in developmental biology. Many tissue-specific genes are involved in the pathogenesis of complex human diseases. However, experimental identification of tissue-specific genes is time consuming and difficult. The accurate predictions of tissue-specific gene targets could provide useful information for biomarker development and drug target identification. Results In this study, we have developed a machine learning approach for predicting the human tissue-specific genes using microarray expression data. The lists of known tissue-specific genes for different tissues were collected from UniProt database, and the expression data retrieved from the previously compiled dataset according to the lists were used for input vector encoding. Random Forests (RFs and Support Vector Machines (SVMs were used to construct accurate classifiers. The RF classifiers were found to outperform SVM models for tissue-specific gene prediction. The results suggest that the candidate genes for brain or liver specific expression can provide valuable information for further experimental studies. Our approach was also applied for identifying tissue-selective gene targets for different types of tissues. Conclusions A machine learning approach has been developed for accurately identifying the candidate genes for tissue specific/selective expression. The approach provides an efficient way to select some interesting genes for developing new biomedical markers and improve our knowledge of tissue-specific expression.

  13. Sci—Thur AM: YIS - 02: Radiogenomic Modeling of Normal Tissue Toxicities in Prostate Cancer Patients Receiving Hypofractionated Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Coates, J [Department of Oncology, Medical Physics Unit, McGill University Health Center, Montreal, QC (Canada); Jeyaseelan, K; Ybarra, N; David, M; Faria, S; Souhami, L; Cury, F; Duclos, M; El Naqa, I [Department of Oncology, Medical Physics Unit, McGill University Health Center, Montreal, QC (Canada); Department of Oncology, Radiation Oncology Division, McGill University Health Centre, Montreal, QC Canada (Canada)

    2014-08-15

    Inter-patient radiation sensitivity variability has recently been shown to have a genetic component. This genetic component may play a key role in explaining the fluctuating rates of radiation-induced toxicities (RITs). Single nucleotide polymorphisms (SNPs) have thus far yielded inconsistent results in delineating RITs while copy number variations (CNVs) have not yet been investigated for such purposes. We explore a radiogenomic modeling approach to investigate the association of CNVs and SNPs, along with clinical and dosimetric variables, in radiation induced rectal bleeding (RB) and erectile dysfunction (ED) in prostate cancer patients treated with curative hypofractionated irradiation. A cohort of 62 prostate cancer patients who underwent hypofractionated radiotherapy (66 Gy in 22 fractions) between 2002 to 2010 were retrospectively genotyped for CNV and SNP rs5489 in the xrcc1 DNA repair gene. Late toxicity rates for RB grade 2 and 3 and grade 3 alone were 29.0% and 12.9%, respectively. ED toxicity was found to be 62.9%. Radiogenomic model performance was evaluated using receiver operating characteristic area under the curve (AUC) and resampling by cross-validation. Binary variables were evaluated using Chi-squared contingency table analysis and multivariate models by Spearman's rank correlation coefficient (rs). Ten patients were found to have three copies of xrcc1 CNV (RB: χ{sup 2}=14.6, p<0.001 and ED: χ{sup 2}=4.88, p=0.0272) and twelve had heterozygous rs25489 SNP (RB: χ{sup 2}=0.278, p=0.599 and ED: χ{sup 2}=0.112, p=0.732). Radiogenomic modeling yielded significant, cross-validated NTCP models for RB (AUC=0.665) and ED (AUC=0.754). These results indicate that CNVs may be potential predictive biomarkers of both late ED and RB.

  14. Characterizing the Hypermutated Subtype of Advanced Prostate Cancer as a Predictive Biomarker for Precision Medicine

    Science.gov (United States)

    2017-10-01

    was a think tank of leading prostate cancer researchers focused on the question of oligo- metastatic disease. I was part of the program organizing...Wilke, J., Wilder-Romans, K., Dhanireddy, S., Engelke, C., et al. (2014). Therapeutic targeting of BET bromodomain proteins in castration-resistant...begun to make a positive difference in the lives of men with advanced prostate cancer. Attention to how we might similarly adjust the way we think

  15. Multivariate analysis of factors predicting prostate dose in intensity-modulated radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Tomita, Tsuneyuki [Division of Radiology, Osaka Red Cross Hospital, Osaka (Japan); Nakamura, Mitsuhiro, E-mail: m_nkmr@kuhp.kyoto-u.ac.jp [Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Hirose, Yoshinori; Kitsuda, Kenji; Notogawa, Takuya; Miki, Katsuhito [Division of Radiology, Osaka Red Cross Hospital, Osaka (Japan); Nakamura, Kiyonao; Ishigaki, Takashi [Department of Radiation Oncology, Osaka Red Cross Hospital, Osaka (Japan)

    2014-01-01

    We conducted a multivariate analysis to determine relationships between prostate radiation dose and the state of surrounding organs, including organ volumes and the internal angle of the levator ani muscle (LAM), based on cone-beam computed tomography (CBCT) images after bone matching. We analyzed 270 CBCT data sets from 30 consecutive patients receiving intensity-modulated radiation therapy for prostate cancer. With patients in the supine position on a couch with the HipFix system, data for center of mass (COM) displacement of the prostate and the state of individual organs were acquired and compared between planning CT and CBCT scans. Dose distributions were then recalculated based on CBCT images. The relative effects of factors on the variance in COM, dose covering 95% of the prostate volume (D{sub 95%}), and percentage of prostate volume covered by the 100% isodose line (V{sub 100%}) were evaluated by a backward stepwise multiple regression analysis. COM displacement in the anterior-posterior direction (COM{sub AP}) correlated significantly with the rectum volume (δVr) and the internal LAM angle (δθ; R = 0.63). Weak correlations were seen for COM in the left-right (R = 0.18) and superior-inferior directions (R = 0.31). Strong correlations between COM{sub AP} and prostate D{sub 95%} and V{sub 100%} were observed (R ≥ 0.69). Additionally, the change ratios in δVr and δθ remained as predictors of prostate D{sub 95%} and V{sub 100%}. This study shows statistically that maintaining the same rectum volume and LAM state for both the planning CT simulation and treatment is important to ensure the correct prostate dose in the supine position with bone matching.

  16. A Multi-Center Prospective Study to Validate an Algorithm Using Urine and Plasma Biomarkers for Predicting Gleason ≥3+4 Prostate Cancer on Biopsy

    DEFF Research Database (Denmark)

    Albitar, Maher; Ma, Wanlong; Lund, Lars

    2017-01-01

    a prospective multicenter study recruiting patients from community-based practices. Patients and Methods: Urine and plasma samples from 2528 men were tested prospectively. Results were correlated with biopsy findings, if a biopsy was performed as deemed necessary by the practicing urologist. Of the 2528......Background: Unnecessary biopsies and overdiagnosis of prostate cancer (PCa) remain a serious healthcare problem. We have previously shown that urine- and plasma-based prostate-specific biomarkers when combined can predict high grade prostate cancer (PCa). To further validate this test, we performed...... of high grade prostate cancer with negative predictive value (NPV) of 90% to 97% for Gleason ≥3+4 and between 98% to 99% for Gleason ≥4+3....

  17. Differentiation of prostatitis and prostate cancer using the Prostate Imaging-Reporting and Data System (PI-RADS).

    Science.gov (United States)

    Meier-Schroers, Michael; Kukuk, Guido; Wolter, Karsten; Decker, Georges; Fischer, Stefan; Marx, Christian; Traeber, Frank; Sprinkart, Alois Martin; Block, Wolfgang; Schild, Hans Heinz; Willinek, Winfried

    2016-07-01

    To determine if prostate cancer (PCa) and prostatitis can be differentiated by using PI-RADS. 3T MR images of 68 patients with 85 cancer suspicious lesions were analyzed. The findings were correlated with histopathology. T2w imaging (T2WI), diffusion weighted imaging (DWI), dynamic contrast enhancement (DCE), and MR-Spectroscopy (MRS) were acquired. Every lesion was given a single PI-RADS score for each parameter, as well as a sum score and a PI-RADS v2 score. Furthermore, T2-morphology, ADC-value, perfusion type, citrate/choline-level, and localization were evaluated. 44 of 85 lesions showed PCa (51.8%), 21 chronic prostatitis (24.7%), and 20 other benign tissue such as hyperplasia or fibromuscular tissue (23.5%). The single PI-RADS score for T2WI, DWI, DCE, as well as the aggregated score including and not including MRS, and the PI-RADS v2-score were all significantly higher for PCa than for prostatitis or other tissue (pprostatitis than for other tissue (p=0.029 and p=0.020), whereas the other parameters were not different. Prostatitis usually presented borderline pathological PI-RADS scores, showed restricted diffusion with ADC≥900mm(2)/s in 100% of cases, was more often indistinctly hypointense on T2WI (66.7%), and localized in the transitional zone (57.1%). An ADC≥900mm(2)/s achieved the highest predictive value for prostatitis (AUC=0.859). Prostatitis can be differentiated from PCa using PI-RADS, since all available parameters are more distinct in cases of cancer. However, there is significant overlap between prostatitis and other benign findings, thus PI-RADS is only suitable to a limited extent for the primary assessment of prostatitis. Restricted diffusion with ADC≥900mm(2)/s is believed to be a good indicator for prostatitis. MRS can help to distinguish between prostatitis and other tissue. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Prediction of cartilaginous tissue repair after knee joint distraction

    NARCIS (Netherlands)

    van der Woude, J A D; Welsing, P M; van Roermund, P M; Custers, R J H; Kuchuk, N O; Lafeber, F P J G G

    2016-01-01

    BACKGROUND: For young patients (<65years), knee joint distraction (KJD) may be a joint-saving treatment option for end-stage knee osteoarthritis. Distracting the femur from the tibia by five millimeters for six to eight weeks using an external fixation frame results in cartilaginous tissue repair,

  19. Genetic markers for prediction of normal tissue toxicity after radiotherapy

    DEFF Research Database (Denmark)

    Alsner, Jan; Andreassen, Christian Nicolaj; Overgaard, Jens

    2008-01-01

    During the last decade, a number of studies have supported the hypothesis that there is an important genetic component to the observed interpatient variability in normal tissue toxicity after radiotherapy. This review summarizes the candidate gene association studies published so far on the risk...

  20. Incorporation of lysosomal sequestration in the mechanistic model for prediction of tissue distribution of basic drugs.

    Science.gov (United States)

    Assmus, Frauke; Houston, J Brian; Galetin, Aleksandra

    2017-11-15

    The prediction of tissue-to-plasma water partition coefficients (Kpu) from in vitro and in silico data using the tissue-composition based model (Rodgers & Rowland, J Pharm Sci. 2005, 94(6):1237-48.) is well established. However, distribution of basic drugs, in particular into lysosome-rich lung tissue, tends to be under-predicted by this approach. The aim of this study was to develop an extended mechanistic model for the prediction of Kpu which accounts for lysosomal sequestration and the contribution of different cell types in the tissue of interest. The extended model is based on compound-specific physicochemical properties and tissue composition data to describe drug ionization, distribution into tissue water and drug binding to neutral lipids, neutral phospholipids and acidic phospholipids in tissues, including lysosomes. Physiological data on the types of cells contributing to lung, kidney and liver, their lysosomal content and lysosomal pH were collated from the literature. The predictive power of the extended mechanistic model was evaluated using a dataset of 28 basic drugs (pK a ≥7.8, 17 β-blockers, 11 structurally diverse drugs) for which experimentally determined Kpu data in rat tissue have been reported. Accounting for the lysosomal sequestration in the extended mechanistic model improved the accuracy of Kpu predictions in lung compared to the original Rodgers model (56% drugs within 2-fold or 88% within 3-fold of observed values). Reduction in the extent of Kpu under-prediction was also evident in liver and kidney. However, consideration of lysosomal sequestration increased the occurrence of over-predictions, yielding overall comparable model performances for kidney and liver, with 68% and 54% of Kpu values within 2-fold error, respectively. High lysosomal concentration ratios relative to cytosol (>1000-fold) were predicted for the drugs investigated; the extent differed depending on the lysosomal pH and concentration of acidic phospholipids among

  1. Is epicardial adipose tissue, assessed by echocardiography, a reliable method for visceral adipose tissue prediction?

    Science.gov (United States)

    Silaghi, Alina Cristina; Poantă, Laura; Valea, Ana; Pais, Raluca; Silaghi, Horatiu

    2011-03-01

    Epicardial adipose tissue is an ectopic fat storage at the heart surface in direct contact with the coronary arteries. It is considered a metabolically active tissue, being a local source of pro-inflammatory factors that contribute to the pathogenesis of coronary artery disease. The AIM of our study was to establish correlations between echocardiographic assessment of epicardial adipose tissue and anthropometric and ultrasound measurements of the central and peripheral fat depots. The study was conducted on 22 patients with or without coronaropathy. Epicardial adipose tissue was measured using Aloka Prosound α 10 machine with a 3.5-7.5 MHz variable-frequency transducer and subcutaneous and visceral fat with Esaote Megas GPX machine and 3.5-7.5 MHz variable frequency transducer. Epicardial adipose tissue measured by echocardiography is correlated with waist circumference (p < 0.05), visceral adipose tissue thickness measured by ultrasonography (US) and is not correlated with body mass index (p = 0.315), hip and thigh circumference or subcutaneous fat thickness measured by US. Our study confirms that US assessment of epicardial fat correlates with anthropometric and US measurements of the central fat, representing an indirect but reliable marker of the visceral fat.

  2. PROSTATE-SPECIFIC ANTIGEN A Clue for the Prostatic Origin of Metastasis

    OpenAIRE

    MANABE, Toshiaki; TSUKAYAMA, Chotatsu; YAMAGUCHI, Masae; YAMASHITA, Koshi

    1983-01-01

    The prostate-specific antigen is a recently purified glycoprotein which is present only in the prostatic gland. In order to confirm the usefulness of this protein in isolating prostatic carcinomas from socalled metastatic carcinomas of unknown primary site, we immunohistochemically studied 19 non-neoplastic prostatic tissue, 18 primary carcinomas of the prostate, and 32 non-prostatic adenocarcinomas. From our study, we concluded that PSA is highly specific for the prostatic carcinomas. The ab...

  3. Near real-time automated dose restoration in IMPT to compensate for daily tissue density variations in prostate cancer

    Science.gov (United States)

    Jagt, Thyrza; Breedveld, Sebastiaan; van de Water, Steven; Heijmen, Ben; Hoogeman, Mischa

    2017-06-01

    Proton therapy is very sensitive to daily density changes along the pencil beam paths. The purpose of this study is to develop and evaluate an automated method for adaptation of IMPT plans to compensate for these daily tissue density variations. A two-step restoration method for ‘densities-of-the-day’ was created: (1) restoration of spot positions (Bragg peaks) by adapting the energy of each pencil beam to the new water equivalent path length; and (2) re-optimization of pencil beam weights by minimizing the dosimetric difference with the planned dose distribution, using a fast and exact quadratic solver. The method was developed and evaluated using 8-10 repeat CT scans of 10 prostate cancer patients. Experiments demonstrated that giving a high weight to the PTV in the re-optimization resulted in clinically acceptable restorations. For all scans we obtained V 95%  ⩾  98% and V 107%  ⩽  2%. For the bladder, the differences between the restored and the intended treatment plan were below  +2 Gy and  +2%-point. The rectum differences were below  +2 Gy and  +2%-point for 90% of the scans. In the remaining scans the rectum was filled with air, which partly overlapped with the PTV. The air cavity distorted the Bragg peak resulting in less favorable rectum doses.

  4. Comparative evaluation of urinary PCA3 and TMPRSS2: ERG scores and serum PHI in predicting prostate cancer aggressiveness.

    Science.gov (United States)

    Tallon, Lucile; Luangphakdy, Devillier; Ruffion, Alain; Colombel, Marc; Devonec, Marian; Champetier, Denis; Paparel, Philippe; Decaussin-Petrucci, Myriam; Perrin, Paul; Vlaeminck-Guillem, Virginie

    2014-07-30

    It has been suggested that urinary PCA3 and TMPRSS2:ERG fusion tests and serum PHI correlate to cancer aggressiveness-related pathological criteria at prostatectomy. To evaluate and compare their ability in predicting prostate cancer aggressiveness, PHI and urinary PCA3 and TMPRSS2:ERG (T2) scores were assessed in 154 patients who underwent radical prostatectomy for biopsy-proven prostate cancer. Univariate and multivariate analyses using logistic regression and decision curve analyses were performed. All three markers were predictors of a tumor volume≥0.5 mL. Only PHI predicted Gleason score≥7. T2 score and PHI were both independent predictors of extracapsular extension(≥pT3), while multifocality was only predicted by PCA3 score. Moreover, when compared to a base model (age, digital rectal examination, serum PSA, and Gleason sum at biopsy), the addition of both PCA3 score and PHI to the base model induced a significant increase (+12%) when predicting tumor volume>0.5 mL. PHI and urinary PCA3 and T2 scores can be considered as complementary predictors of cancer aggressiveness at prostatectomy.

  5. The prostate health index PHI predicts oncological outcome and biochemical recurrence after radical prostatectomy - analysis in 437 patients.

    Science.gov (United States)

    Maxeiner, Andreas; Kilic, Ergin; Matalon, Julia; Friedersdorff, Frank; Miller, Kurt; Jung, Klaus; Stephan, Carsten; Busch, Jonas

    2017-10-03

    The purpose of this study was to investigate the Prostate-Health-Index (PHI) for pathological outcome prediction following radical prostatectomy and also for biochemical recurrence prediction in comparison to established parameters such as Gleason-score, pathological tumor stage, resection status (R0/1) and prostate-specific antigen (PSA). Out of a cohort of 460 cases with preoperative PHI-measurements (World Health Organization calibration: Beckman Coulter Access-2-Immunoassay) between 2001 and 2014, 437 patients with complete follow up data were included. From these 437 patients, 87 (19.9%) developed a biochemical recurrence. Patient characteristics were compared by using chi-square test. Predictors were analyzed by multivariate adjusted logistic and Cox regression. The median follow up for a biochemical recurrence was 65 (range 3-161) months. PHI, PSA, [-2]proPSA, PHI- and PSA-density performed as significant variables (p PHI, PSA, %fPSA, [-2]proPSA, PHI- and PSA-density significantly discriminated between stages PHI. In biochemical recurrence prediction PHI, PSA, [-2]proPSA, PHI- and PSA-density were the strongest predictors. In conclusion, due to heterogeneity of time spans to biochemical recurrence, longer follow up periods are crucial. This study with a median follow up of more than 5 years, confirmed a clinical value for PHI as an independent biomarker essential for biochemical recurrence prediction.

  6. Comparative Evaluation of Urinary PCA3 and TMPRSS2: ERG Scores and Serum PHI in Predicting Prostate Cancer Aggressiveness

    Directory of Open Access Journals (Sweden)

    Lucile Tallon

    2014-07-01

    Full Text Available It has been suggested that urinary PCA3 and TMPRSS2:ERG fusion tests and serum PHI correlate to cancer aggressiveness-related pathological criteria at prostatectomy. To evaluate and compare their ability in predicting prostate cancer aggressiveness, PHI and urinary PCA3 and TMPRSS2:ERG (T2 scores were assessed in 154 patients who underwent radical prostatectomy for biopsy-proven prostate cancer. Univariate and multivariate analyses using logistic regression and decision curve analyses were performed. All three markers were predictors of a tumor volume ≥0.5 mL. Only PHI predicted Gleason score ≥7. T2 score and PHI were both independent predictors of extracapsular extension (≥pT3, while multifocality was only predicted by PCA3 score. Moreover, when compared to a base model (age, digital rectal examination, serum PSA, and Gleason sum at biopsy, the addition of both PCA3 score and PHI to the base model induced a significant increase (+12% when predicting tumor volume >0.5 mL. PHI and urinary PCA3 and T2 scores can be considered as complementary predictors of cancer aggressiveness at prostatectomy.

  7. Fluorescent biopsy of biological tissues in differentiation of benign and malignant tumors of prostate

    Science.gov (United States)

    Trifoniuk, L. I.; Ushenko, Yu. A.; Sidor, M. I.; Minzer, O. P.; Gritsyuk, M. V.; Novakovskaya, O. Y.

    2014-08-01

    The work consists of investigation results of diagnostic efficiency of a new azimuthally stable Mueller-matrix method of analysis of laser autofluorescence coordinate distributions of biological tissues histological sections. A new model of generalized optical anisotropy of biological tissues protein networks is proposed in order to define the processes of laser autofluorescence. The influence of complex mechanisms of both phase anisotropy (linear birefringence and optical activity) and linear (circular) dichroism is taken into account. The interconnections between the azimuthally stable Mueller-matrix elements characterizing laser autofluorescence and different mechanisms of optical anisotropy are determined. The statistic analysis of coordinate distributions of such Mueller-matrix rotation invariants is proposed. Thereupon the quantitative criteria (statistic moments of the 1st to the 4th order) of differentiation of histological sections of uterus wall tumor - group 1 (dysplasia) and group 2 (adenocarcinoma) are estimated.

  8. Optical coherence elastography (OCE) as a method for identifying benign and malignant prostate biopsies

    Science.gov (United States)

    Li, Chunhui; Guan, Guangying; Ling, Yuting; Lang, Stephen; Wang, Ruikang K.; Huang, Zhihong; Nabi, Ghulam

    2015-03-01

    Objectives. Prostate cancer is the most frequently diagnosed malignancy in men. Digital rectal examination (DRE) - a known clinical tool based on alteration in the mechanical properties of tissues due to cancer has traditionally been used for screening prostate cancer. Essentially, DRE estimates relative stiffness of cancerous and normal prostate tissue. Optical coherence elastography (OCE) are new optical imaging techniques capable of providing cross-sectional imaging of tissue microstructure as well as elastogram in vivo and in real time. In this preliminary study, OCE was used in the setting of the human prostate biopsies ex vivo, and the images acquired were compared with those obtained using standard histopathologic methods. Methods. 120 prostate biopsies were obtained by TRUS guided needle biopsy procedures from 9 patients with clinically suspected cancer of the prostate. The biopsies were approximately 0.8mm in diameter and 12mm in length, and prepared in Formalin solution. Quantitative assessment of biopsy samples using OCE was obtained in kilopascals (kPa) before histopathologic evaluation. The results obtained from OCE and standard histopathologic evaluation were compared provided the cross-validation. Sensitivity, specificity, and positive and negative predictive values were calculated for OCE (histopathology was a reference standard). Results. OCE could provide quantitative elasticity properties of prostate biopsies within benign prostate tissue, prostatic intraepithelial neoplasia, atypical hyperplasia and malignant prostate cancer. Data analysed showed that the sensitivity and specificity of OCE for PCa detection were 1 and 0.91, respectively. PCa had significantly higher stiffness values compared to benign tissues, with a trend of increasing in stiffness with increasing of malignancy. Conclusions. Using OCE, microscopic resolution elastogram is promising in diagnosis of human prostatic diseases. Further studies using this technique to improve the

  9. Predictive value of bcl-2 immunoreactivity in prostate cancer patients treated with radiotherapy

    International Nuclear Information System (INIS)

    Bylund, A.; Widmark, A.; Stattin, P.; Bergh, A.

    1998-01-01

    Background and purpose: Recent experimental evidence suggests that overexpression of bcl-2, a protein functioning by blocking apoptosis, may influence the treatment outcome in human tumours, including prostate cancer. To test the clinical implications of this hypothesis, tumours from patients with prostate cancer treated with external beam radiotherapy were investigated for bcl-2 immunoreactivity (IR) and correlated with prognosis and treatment outcome. Materials and methods: Bcl-2 IR was evaluated in archival tumour specimens obtained through transurethral resection from 42 patients with localized prostate cancer (T0-T4, N0 and M0). Bcl-2 IR expression was related to stage, grade and cancer-specific survival. Specimens were obtained prior to administrating routine radiotherapy for all patients. Results: Bcl-2 IR was present in 19/42 (45%) tumours. The bcl-2-positive patients had a significantly longer cancer-specific survival than the bcl-2-negative patients (10.3 versus 3.4 years, P<0.04). At follow-up (7-19 years), nine patients were still alive, 26 patients had died of prostate cancer and seven patients had died of other causes. Conclusions: This study indicates that pre-treatment bcl-2 overexpression is related to a favourable outcome in prostate cancer treated with radiotherapy. Low bcl-2 along with a high stage may be a predictor of poor prognosis and these patients might benefit from additional treatment. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  10. Prostate Ultrasound

    Medline Plus

    Full Text Available ... Test/Treatment Patient Type Screening/Wellness Disease/Condition Safety En Español More Info Images/Videos About Us ... in which a needle is used to sample cells (tissue) from an abnormal area in the prostate gland for later laboratory testing. ... Do you have a personal ...

  11. Prostate Ultrasound

    Medline Plus

    Full Text Available ... exam or prostate cancer screening exam. an elevated blood test result. difficulty urinating. Because ultrasound provides real-time images, it also can be used to guide procedures such as needle biopsies , in which a needle is used to sample cells (tissue) from an abnormal area in the ...

  12. Sensitivity of tissue differentiation and bone healing predictions to tissue properties

    NARCIS (Netherlands)

    Isaksson, H.E.; Donkelaar, van C.C.; Ito, K.

    2009-01-01

    Computational models are employed as tools to investigate possible mechano-regulation pathways for tissue differentiation and bone healing. However, current models do not account for the uncertainty in input parameters, and often include assumptions about parameter values that are not yet

  13. Impact of margin on tumour and normal tissue dosimetry in patients treated with IMRT using an endorectal balloon for prostate immobilization

    International Nuclear Information System (INIS)

    Ahmad, S.

    2004-01-01

    Full text: In treatment of prostate cancer with IMRT (Intensity Modulated Radiation Therapy), clinical target volume margin is determined by organ motion and set-up error. However, the margin width that achieves the desired dose escalation while minimizing normal tissue exposure is dependent upon the patient immobilization and/or organ localization techniques. In this study, we compare the impact of margin width on the dosimetry of tumour and normal tissues using the endorectal balloon for prostate immobilization. IMRT plans were generated for ten patients using margin widths of 0, 3, 5, 8 and 10 mm. Patients had a planning CT scan in the prone position with an endorectal balloon filled with 100 cc of air for prostate immobilization. The Corvus version 3.0.11 was used for treatment planning. The dose for the prostate and seminal vesicles was 70 Gy in 2 Gy per fractions, prescribed at the 83% isodose line. Dose restrictions to normal tissues were as follows: 33% of bladder was allowed to receive above 65 Gy, 15% of rectum above 68 Gy and 10% of femurs above 45 Gy. Analysis of Variance was used to compare the target and normal tissue doses. Tumour control probability and normal tissue complication probability calculations are currently being performed and will be presented. The mean doses ranged from 73.93 to 75.31 Gy for the prostate and from 73.71 to 75.31 Gy for the seminal vesicles. A 10 mm margin produced significantly lower mean doses compared to 0 or 5 mm for both targets (prostate p 0.062). For bladder and rectum the mean doses ranged from 18.49 to 22.30 Gy (p=0.605) and from 29.34 to 31.33 Gy (p=0.135), respectively, while the percent rectal volumes above 68 Gy were significantly higher for margins of 5, 8 and 10 mm (p<0.006) ranging from 10.72% to 15.81%. Mean doses to the femurs and pelvis were significantly higher for 8 and 10 mm margins, ranging from 20.9 to 29.39 Gy for femurs (p<0.015) and from 15.05 to 19.98 Gy for pelvis (p<0.0005). Also the percent

  14. Impact of statistical learning methods on the predictive power of multivariate normal tissue complication probability models

    NARCIS (Netherlands)

    Xu, Cheng-Jian; van der Schaaf, Arjen; Schilstra, Cornelis; Langendijk, Johannes A.; van t Veld, Aart A.

    2012-01-01

    PURPOSE: To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. METHODS AND MATERIALS: In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator

  15. Prognostic value of tissue Doppler imaging for predicting ventricular arrhythmias and cardiovascular mortality in ischaemic cardiomyopathy

    DEFF Research Database (Denmark)

    Biering-Sørensen, Tor; Olsen, Flemming Javier; Storm, Katrine

    2016-01-01

    AIMS: Only 30% of patients receiving an implantable cardioverter defibrillator (ICD) for primary prevention receive appropriately therapy. We sought to investigate the value of tissue Doppler imaging (TDI) to predict ventricular tachycardia (VT), ventricular fibrillation (VF), and cardiovascular...

  16. Nonlinear joint models for individual dynamic prediction of risk of death using Hamiltonian Monte Carlo: application to metastatic prostate cancer

    Directory of Open Access Journals (Sweden)

    Solène Desmée

    2017-07-01

    Full Text Available Abstract Background Joint models of longitudinal and time-to-event data are increasingly used to perform individual dynamic prediction of a risk of event. However the difficulty to perform inference in nonlinear models and to calculate the distribution of individual parameters has long limited this approach to linear mixed-effect models for the longitudinal part. Here we use a Bayesian algorithm and a nonlinear joint model to calculate individual dynamic predictions. We apply this approach to predict the risk of death in metastatic castration-resistant prostate cancer (mCRPC patients with frequent Prostate-Specific Antigen (PSA measurements. Methods A joint model is built using a large population of 400 mCRPC patients where PSA kinetics is described by a biexponential function and the hazard function is a PSA-dependent function. Using Hamiltonian Monte Carlo algorithm implemented in Stan software and the estimated population parameters in this population as priors, the a posteriori distribution of the hazard function is computed for a new patient knowing his PSA measurements until a given landmark time. Time-dependent area under the ROC curve (AUC and Brier score are derived to assess discrimination and calibration of the model predictions, first on 200 simulated patients and then on 196 real patients that are not included to build the model. Results Satisfying coverage probabilities of Monte Carlo prediction intervals are obtained for longitudinal and hazard functions. Individual dynamic predictions provide good predictive performances for landmark times larger than 12 months and horizon time of up to 18 months for both simulated and real data. Conclusions As nonlinear joint models can characterize the kinetics of biomarkers and their link with a time-to-event, this approach could be useful to improve patient’s follow-up and the early detection of most at risk patients.

  17. Seed Implant Retention Score Predicts the Risk of Prolonged Urinary Retention After Prostate Brachytherapy

    International Nuclear Information System (INIS)

    Lee, Hoon K.; Adams, Marc T.; Shi, Qiuhu; Basillote, Jay; LaMonica, Joanne; Miranda, Luis; Motta, Joseph

    2010-01-01

    Purpose: To risk-stratify patients for urinary retention after prostate brachytherapy according to a novel seed implant retention score (SIRS). Patients and Methods: A total of 835 patients underwent transperineal prostate seed implant from March 1993 to January 2007; 197 patients had 125 I and 638 patients had 103 Pd brachytherapy. Four hundred ninety-four patients had supplemental external-beam radiation. The final downsized prostate volume was used for the 424 patients who had neoadjuvant hormone therapy. Retention was defined as reinsertion of a Foley catheter after the implant. Results: Retention developed in 7.4% of patients, with an average duration of 6.7 weeks. On univariate analysis, implant without supplemental external-beam radiation (10% vs. 5.6%; p = 0.02), neoadjuvant hormone therapy (9.4% vs. 5.4%; p = 0.02), baseline α-blocker use (12.5% vs. 6.3%; p = 0.008), and increased prostate volume (13.4% vs. 6.9% vs. 2.9%, >45 cm 3 , 25-45 cm 3 , 3 ; p = 0.0008) were significantly correlated with increased rates of retention. On multivariate analysis, implant without supplemental external-beam radiation, neoadjuvant hormone therapy, baseline α-blocker use, and increased prostate volume were correlated with retention. A novel SIRS was modeled as the combined score of these factors, ranging from 0 to 5. There was a significant correlation between the SIRS and retention (p < 0.0001). The rates of retention were 0, 4%, 5.6%, 9%, 20.9%, and 36.4% for SIRS of 0 to 5, respectively. Conclusions: The SIRS may identify patients who are at high risk for prolonged retention after prostate brachytherapy. A prospective validation study of the SIRS is planned.

  18. Alterations of global histone H4K20 methylation during prostate carcinogenesis

    Directory of Open Access Journals (Sweden)

    Behbahani Turang E

    2012-03-01

    Full Text Available Abstract Background Global histone modifications have been implicated in the progression of various tumour entities. Our study was designed to assess global methylation levels of histone 4 lysine 20 (H4K20me1-3 at different stages of prostate cancer (PCA carcinogenesis. Methods Global H4K20 methylation levels were evaluated using a tissue microarray in patients with clinically localized PCA (n = 113, non-malignant prostate disease (n = 27, metastatic hormone-naive PCA (mPCA, n = 30 and castration-resistant PCA (CRPC, n = 34. Immunohistochemistry was performed to assess global levels of H4K20 methylation levels. Results Similar proportions of the normal, PCA, and mPCA prostate tissues showed strong H4K20me3 staining. CRPC tissue analysis showed the weakest immunostaining levels of H4K20me1 and H4K20me2, compared to other prostate tissues. H4K20me2 methylation levels indicated significant differences in examined tissues except for normal prostate versus PCA tissue. H4K20me1 differentiates CRPC from other prostate tissues. H4K20me1 was significantly correlated with lymph node metastases, and H4K20me2 showed a significant correlation with the Gleason score. However, H4K20 methylation levels failed to predict PSA recurrence after radical prostatectomy. Conclusions H4K20 methylation levels constitute valuable markers for the dynamic process of prostate cancer carcinogenesis.

  19. Prediction and measurement of thermally induced cambial tissue necrosis in tree stems

    Science.gov (United States)

    Joshua L. Jones; Brent W. Webb; Bret W. Butler; Matthew B. Dickinson; Daniel Jimenez; James Reardon; Anthony S. Bova

    2006-01-01

    A model for fire-induced heating in tree stems is linked to a recently reported model for tissue necrosis. The combined model produces cambial tissue necrosis predictions in a tree stem as a function of heating rate, heating time, tree species, and stem diameter. Model accuracy is evaluated by comparison with experimental measurements in two hardwood and two softwood...

  20. Measurements of free and total PSA, tissue polypeptide-specific antigen (TPS), and CYFRA 21-1 in prostate cancer patients under intermittent androgen suppression therapy.

    Science.gov (United States)

    Theyer, G; Dürer, A; Theyer, U; Haberl, I; Ulsperger, E; Baumgartner, G; Hamilton, G

    1999-10-01

    The present study evaluated monthly measurements of free and total prostate-specific antigen (PSA), and the tumor proliferation markers tissue polypeptide-specific antigen (TPS) and cytokeratin fragment 21-1 (CYFRA 21-1) in patients with advanced prostate cancer receiving intermittent androgen suppression therapy (IAS). Thirty-four men received alternating cycles of 8 month androgen suppression and treatment cessation (mean duration, 10.3 months) until PSA increased to >20 microg/l. Measurements of testosterone, percentage of free PSA, TPS, and CYFRA 21-1 were performed using ELISA and RIA assays. Periods of androgen suppression resulted in reversible reductions of testosterone (from 6 +/- 0.8 to IAS cycle. TPS showed a decrease of 50% after 3 months, and CYFRA 21-1 a 25% decrease after 7 months of androgen suppression treatment. During treatment cessation, TPS exceeded the normal cutoff value of 90 U/l late in tumor regrowth (9-11 months), whereas CYFRA 21-1 remained below the normal cutoff value of 3.3 ng/ml. PSA is the best and most sensitive marker of prostate cancer regression and regrowth during IAS cycles of the markers tested in this study. Free PSA constitutes approximately 15% of total PSA (range, 5-32%), and its percentage showed no significant change during IAS cycles. The TPS and CYFRA 21-1 proliferation marker changes in IAS seem to be related mainly to effects on normal androgen-dependent tissues. Copyright 1999 Wiley-Liss, Inc.

  1. The role of nuclear medicine diagnostic technology in prediction of prostate carcinoma in Sudanese individuals

    International Nuclear Information System (INIS)

    Auhamed, H. S. H.

    2011-03-01

    Prostate cancer is one of the most common malignancies worldwide, with an estimated 40,000 new case diagnosed annually. Insulin-like growth factor-1 (IGF-1) is important to the growth and function of prostate gland, but its incidence and mortality have been associated with increased circulating IGF-1 levels and this causes a high risk to the prostate gland cells in development of cancer. To fulfill these hypotheses we do a prospective study of prostate gland in Sudanese men at the Physicians Urology Health department in Khartoum State hospitals (2004-2009) to assayed circulating levels of IGF-1, PSA, E2 and testosterone among 110 known cases of prostate cancer (Ca.P), 110 benign prostate hyperplasia (BPH) and 110 matched controls subjects (CG). Using non isotopic enzyme methods of Enzyme Linked Sorbent Assay (ELISA), kits produced from Germany DRG company and sensitive micro plate reader and SPSS and ANOVAS one way statistic programme to analysis the data. So when we compare these three groups with ages, types of cancers, and the IGF-1, PSA, E2 and testosterone parameters, there was significant (p=0.04) and the associations between these hormones parameters was (p=0.01). Also when we compare the IGF-1 levels at 95% of upper quartiles of confidence interval in CG group (180ng/ml) with the IGF-1 levels at 25% of lower quartiles of confidence interval in the (Ca.P) and (BPH) group (165ng/ml) and (134ng/ml) respectively, the CG-IGF-1 group was higher than (Ca.P and BPH) groups at these percentiles, with associations between them of (p=0.05). This apparent discrepancy of the risk fallen to the normal (CG) group can be explained using the risk ratio (RR), odds ratio (OR) and confidence interval (CI) with Ca.P patients groups, (OR 2.4, 95% CI 0.71-7.9) (RR 2.3, 95% C10.7-7.1), showing that the risk fallen to the (CG) group was ten (10) times higher than the known cancer patients of the Ca.P, with significant of (p=0.05). So there were associations between high circulating

  2. Development of Decision Support Formulas for the Prediction of Bladder Outlet Obstruction and Prostatic Surgery in Patients With Lower Urinary Tract Symptom/Benign Prostatic Hyperplasia: Part II, External Validation and Usability Testing of a Smartphone App

    Directory of Open Access Journals (Sweden)

    Min Soo Choo

    2017-04-01

    Full Text Available Purpose We aimed to externally validate the prediction model we developed for having bladder outlet obstruction (BOO and requiring prostatic surgery using 2 independent data sets from tertiary referral centers, and also aimed to validate a mobile app for using this model through usability testing. Methods Formulas and nomograms predicting whether a subject has BOO and needs prostatic surgery were validated with an external validation cohort from Seoul National University Bundang Hospital and Seoul Metropolitan Government-Seoul National University Boramae Medical Center between January 2004 and April 2015. A smartphone-based app was developed, and 8 young urologists were enrolled for usability testing to identify any human factor issues of the app. Results A total of 642 patients were included in the external validation cohort. No significant differences were found in the baseline characteristics of major parameters between the original (n=1,179 and the external validation cohort, except for the maximal flow rate. Predictions of requiring prostatic surgery in the validation cohort showed a sensitivity of 80.6%, a specificity of 73.2%, a positive predictive value of 49.7%, and a negative predictive value of 92.0%, and area under receiver operating curve of 0.84. The calibration plot indicated that the predictions have good correspondence. The decision curve showed also a high net benefit. Similar evaluation results using the external validation cohort were seen in the predictions of having BOO. Overall results of the usability test demonstrated that the app was user-friendly with no major human factor issues. Conclusions External validation of these newly developed a prediction model demonstrated a moderate level of discrimination, adequate calibration, and high net benefit gains for predicting both having BOO and requiring prostatic surgery. Also a smartphone app implementing the prediction model was user-friendly with no major human factor issue.

  3. A hybrid approach to advancing quantitative prediction of tissue distribution of basic drugs in human

    International Nuclear Information System (INIS)

    Poulin, Patrick; Ekins, Sean; Theil, Frank-Peter

    2011-01-01

    A general toxicity of basic drugs is related to phospholipidosis in tissues. Therefore, it is essential to predict the tissue distribution of basic drugs to facilitate an initial estimate of that toxicity. The objective of the present study was to further assess the original prediction method that consisted of using the binding to red blood cells measured in vitro for the unbound drug (RBCu) as a surrogate for tissue distribution, by correlating it to unbound tissue:plasma partition coefficients (Kpu) of several tissues, and finally to predict volume of distribution at steady-state (V ss ) in humans under in vivo conditions. This correlation method demonstrated inaccurate predictions of V ss for particular basic drugs that did not follow the original correlation principle. Therefore, the novelty of this study is to provide clarity on the actual hypotheses to identify i) the impact of pharmacological mode of action on the generic correlation of RBCu-Kpu, ii) additional mechanisms of tissue distribution for the outlier drugs, iii) molecular features and properties that differentiate compounds as outliers in the original correlation analysis in order to facilitate its applicability domain alongside the properties already used so far, and finally iv) to present a novel and refined correlation method that is superior to what has been previously published for the prediction of human V ss of basic drugs. Applying a refined correlation method after identifying outliers would facilitate the prediction of more accurate distribution parameters as key inputs used in physiologically based pharmacokinetic (PBPK) and phospholipidosis models.

  4. Normal tissue complication probability: Does simultaneous integrated boost intensity-modulated radiotherapy score over other techniques in treatment of prostate adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Jothy Basu K

    2009-01-01

    Full Text Available Aim: The main objective of this study was to analyze the radiobiological effect of different treatment strategies on high-risk prostate adenocarcinoma. Materials and Methods: Ten cases of high-risk prostate adenocarcinoma were selected for this dosimetric study. Four different treatment strategies used for treating prostate cancer were compared. Conventional four-field box technique covering prostate and nodal volumes followed by three-field conformal boost (3D + 3DCRT, four-field box technique followed by intensity-modulated radiotherapy (IMRT boost (3D + IMRT, IMRT followed by IMRT boost (IMRT + IMRT, and simultaneous integrated boost IMRT (SIBIMRT were compared in terms of tumor control probability (TCP and normal tissue complication probability (NTCP. The dose prescription except for SIBIMRT was 45 Gy in 25 fractions for the prostate and nodal volumes in the initial phase and 27 Gy in 15 fractions for the prostate in the boost phase. For SIBIMRT, equivalent doses were calculated using biologically equivalent dose assuming the α/β ratio of 1.5 Gy with a dose prescription of 60.75 Gy for the gross tumor volume (GTV and 45 Gy for the clinical target volume in 25 fractions. IMRT plans were made with 15-MV equispaced seven coplanar fields. NTCP was calculated using the Lyman-Kutcher-Burman (LKB model. Results: An NTCP of 10.7 ± 0.99%, 8.36 ± 0.66%, 6.72 ± 0.85%, and 1.45 ± 0.11% for the bladder and 14.9 ± 0.99%, 14.04 ± 0.66%, 11.38 ± 0.85%, 5.12 ± 0.11% for the rectum was seen with 3D + 3DCRT, 3D + IMRT, IMRT + IMRT, and SIBIMRT respectively. Conclusions: SIBIMRT had the least NTCP over all other strategies with a reduced treatment time (3 weeks less. It should be the technique of choice for dose escalation in prostate carcinoma.

  5. Prostate Problems

    Science.gov (United States)

    ... know the exact cause of your prostate problem. Prostatitis The cause of prostatitis depends on whether you ... prostate problem in men older than age 50. Prostatitis If you have a UTI, you may be ...

  6. Use of the Charlson Combined Comorbidity Index To Predict Postradiotherapy Quality of Life for Prostate Cancer Patients

    International Nuclear Information System (INIS)

    Wahlgren, Thomas; Levitt, Seymour; Kowalski, Jan; Nilsson, Sten; Brandberg, Yvonne

    2011-01-01

    Purpose: To determine the impact of pretreatment comorbidity on late health-related quality of life (HRQoL) scores after patients have undergone combined radiotherapy for prostate cancer, including high-dose rate brachytherapy boost and hormonal deprivation therapy. Methods and Materials: Results from the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire survey of 158 patients 5 years or more after completion of therapy were used from consecutively accrued subjects treated with curative radiotherapy at our institution, with no signs of disease at the time of questionnaire completion. HRQoL scores were compared with the Charlson combined comorbidity index (CCI), using analysis of covariance and multivariate regression models together with pretreatment factors including tumor stage, tumor grade, pretreatment prostate-specific antigen level, neoadjuvant hormonal treatment, diabetes status, cardiovascular status, and age and Charlson score as separate variables or the composite CCI. Results: An inverse correlation between the two HRQoL domains, long-term global health (QL) and physical function (PF) scores, and the CCI score was observed, indicating an impact of comorbidity in these function areas. Selected pretreatment factors poorly explained the variation in functional HRQoL in the multivariate models; however, a statistically significant impact was found for the CCI (with QL and PF scores) and the presence of diabetes (with QL and emotional function). Cognitive function and social function were not statistically significantly predicted by any of the pretreatment factors. Conclusions: The CCI proved to be valid in this context, but it seems useful mainly in predicting long-term QL and PF scores. Of the other variables investigated, diabetes had more impact than cardiovascular morbidity on HRQoL outcomes in prostate cancer.

  7. Use of the Charlson Combined Comorbidity Index To Predict Postradiotherapy Quality of Life for Prostate Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Wahlgren, Thomas, E-mail: thomas.wahlgren@telia.com [Department of Oncology-Pathology, Karolinska University Hospital and Institutet, Stockholm (Sweden); Levitt, Seymour [Department of Oncology-Pathology, Karolinska University Hospital and Institutet, Stockholm (Sweden); Department of Therapeutic Radiology, University of Minnesota, Minneapolis, Minnesota (United States); Kowalski, Jan [Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm (Sweden); Nilsson, Sten; Brandberg, Yvonne [Department of Oncology-Pathology, Karolinska University Hospital and Institutet, Stockholm (Sweden)

    2011-11-15

    Purpose: To determine the impact of pretreatment comorbidity on late health-related quality of life (HRQoL) scores after patients have undergone combined radiotherapy for prostate cancer, including high-dose rate brachytherapy boost and hormonal deprivation therapy. Methods and Materials: Results from the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire survey of 158 patients 5 years or more after completion of therapy were used from consecutively accrued subjects treated with curative radiotherapy at our institution, with no signs of disease at the time of questionnaire completion. HRQoL scores were compared with the Charlson combined comorbidity index (CCI), using analysis of covariance and multivariate regression models together with pretreatment factors including tumor stage, tumor grade, pretreatment prostate-specific antigen level, neoadjuvant hormonal treatment, diabetes status, cardiovascular status, and age and Charlson score as separate variables or the composite CCI. Results: An inverse correlation between the two HRQoL domains, long-term global health (QL) and physical function (PF) scores, and the CCI score was observed, indicating an impact of comorbidity in these function areas. Selected pretreatment factors poorly explained the variation in functional HRQoL in the multivariate models; however, a statistically significant impact was found for the CCI (with QL and PF scores) and the presence of diabetes (with QL and emotional function). Cognitive function and social function were not statistically significantly predicted by any of the pretreatment factors. Conclusions: The CCI proved to be valid in this context, but it seems useful mainly in predicting long-term QL and PF scores. Of the other variables investigated, diabetes had more impact than cardiovascular morbidity on HRQoL outcomes in prostate cancer.

  8. Urinary EN-2 to predict prostate cancer: Systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Maria Inês da Rosa

    Full Text Available Summary Introduction: Prostate cancer is the second type of cancer diagnosed and the fifth cause of death in men worldwide. Early diagnosis helps to control disease progression. Currently, prostate specific antigen is the standard biomarker, as it has a broad scope of identification and, thus, new and more specific biomarkers must be studied. Objective: To evaluate the accuracy of engrailed-2 protein (EN2 in urine as a prostate cancer biomarker. Method: A comprehensive search was conducted in the period from January 2005 to July 2016 using the following electronic databases: Medline (PubMed, Embase, Cochrane Library and Lilacs. The keywords used in the databases were: "engrailed-2," "EN2," "prostatic neoplasms." The search was limited to humans and there was no language restriction. Critical appraisal of the included studies was performed according to Quadas-2. Statistical analysis was performed using Meta-DiSc® and RevMan 5.3 softwares. Results: A total of 248 studies were identified. After title and abstract screening, 231 studies were removed. A total of 17 studies were read in full and two studies were included in the meta-analysis. The pooled sensitivity was 66% (95CI 0.56-0.75 and specificity was 89% (95CI 0.86-0.92. The DOR was 15.08 (95CI 8.43-26.97. Conclusion: The EN2 test showed high specificity (89% and low sensitivity (66%.

  9. Baseline prostatic specific antigen does not predict the outcome of high energy transurethral microwave thermotherapy

    NARCIS (Netherlands)

    Laguna, M. Pilar; Kiemeney, Lambertus A.; Debruyne, Frans M. J.; de La Rosette, Jean J. M. C. H.

    2002-01-01

    PURPOSE: We assessed the prognostic value of baseline prostate specific antigen (PSA) for outcome after high energy transurethral thermotherapy in patients with lower urinary tract symptoms. MATERIAL AND METHODS: Data were collected prospectively in 404 consecutive patients treated with high energy

  10. ETS Gene Fusions as Predictive Biomarkers of Resistance to Radiation Therapy for Prostate Cancer

    Science.gov (United States)

    2011-08-01

    Award from the Department of Defense (PC094231). This work was supported in part by the National Institutes of Health (R01CA132874 to A.M.C.), Prostate...4506. Li, Z.G., Mathew, P., Yang, J., Starbuck , M.W., Zurita, A.J., Liu, J., Sikes, C., Multani, A.S., Efstathiou, E., Lopez, A., et al. (2008). Androgen

  11. The prediction of blood-tissue partitions, water-skin partitions and skin permeation for agrochemicals.

    Science.gov (United States)

    Abraham, Michael H; Gola, Joelle M R; Ibrahim, Adam; Acree, William E; Liu, Xiangli

    2014-07-01

    There is considerable interest in the blood-tissue distribution of agrochemicals, and a number of researchers have developed experimental methods for in vitro distribution. These methods involve the determination of saline-blood and saline-tissue partitions; not only are they indirect, but they do not yield the required in vivo distribution. The authors set out equations for gas-tissue and blood-tissue distribution, for partition from water into skin and for permeation from water through human skin. Together with Abraham descriptors for the agrochemicals, these equations can be used to predict values for all of these processes. The present predictions compare favourably with experimental in vivo blood-tissue distribution where available. The predictions require no more than simple arithmetic. The present method represents a much easier and much more economic way of estimating blood-tissue partitions than the method that uses saline-blood and saline-tissue partitions. It has the added advantages of yielding the required in vivo partitions and being easily extended to the prediction of partition of agrochemicals from water into skin and permeation from water through skin. © 2013 Society of Chemical Industry.

  12. Prediction of tissue-specific cis-regulatory modules using Bayesian networks and regression trees

    Directory of Open Access Journals (Sweden)

    Chen Xiaoyu

    2007-12-01

    Full Text Available Abstract Background In vertebrates, a large part of gene transcriptional regulation is operated by cis-regulatory modules. These modules are believed to be regulating much of the tissue-specificity of gene expression. Results We develop a Bayesian network approach for identifying cis-regulatory modules likely to regulate tissue-specific expression. The network integrates predicted transcription factor binding site information, transcription factor expression data, and target gene expression data. At its core is a regression tree modeling the effect of combinations of transcription factors bound to a module. A new unsupervised EM-like algorithm is developed to learn the parameters of the network, including the regression tree structure. Conclusion Our approach is shown to accurately identify known human liver and erythroid-specific modules. When applied to the prediction of tissue-specific modules in 10 different tissues, the network predicts a number of important transcription factor combinations whose concerted binding is associated to specific expression.

  13. A new approach to predict human intestinal absorption using porcine intestinal tissue and biorelevant matrices

    NARCIS (Netherlands)

    Westerhout, J.; Steeg, E. van de; Grossouw, D.; Zeijdner, E.E.; Krul, C.A.M.; Verwei, M.; Wortelboer, H.M.

    2014-01-01

    A reliable prediction of the oral bioavailability in humans is crucial and of high interest for pharmaceutical and food industry. The predictive value of currently used in silico methods, in vitro cell lines, ex vivo intestinal tissue and/or in vivo animal studies for human intestinal absorption,

  14. Tissue expression and enzymologic characterization of human prostate specific membrane antigen and its rat and pig orthologs

    Czech Academy of Sciences Publication Activity Database

    Rovenská, Miroslava; Hlouchová, Klára; Šácha, Pavel; Mlčochová, Petra; Horák, Vratislav; Zámečník, J.; Bařinka, C.; Konvalinka, Jan

    2008-01-01

    Roč. 68, č. 2 (2008), s. 171-182 ISSN 0270-4137 R&D Projects: GA MŠk 1M0508; GA ČR GA524/04/0102 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50450515 Keywords : prostate specific membrane antigen * glutamate carboxypeptidase II * animal orthologs * prostate cancer * animal model Subject RIV: CE - Biochemistry Impact factor: 3.069, year: 2008

  15. MRI before and after external beam intensity-modulated radiotherapy of patients with prostate cancer: The feasibility of monitoring of radiation-induced tissue changes using a dynamic contrast-enhanced inversion-prepared dual-contrast gradient echo sequence

    International Nuclear Information System (INIS)

    Franiel, Tobias; Luedemann, Lutz; Taupitz, Matthias; Boehmer, Dirk; Beyersdorff, Dirk

    2009-01-01

    Purpose: To identify and quantify suitable pharmacokinetic MRI parameters for monitoring tissue changes after external beam intensity-modulated radiotherapy of prostate cancer. Material and methods: Six patients with biopsy-proven prostate cancer (initial PSA, 6.0-81.4 ng/ml) underwent MRI at 1.5 T using a combined endorectal/body phased-array coil and a dynamic contrast-enhanced inversion-prepared dual-contrast gradient echo sequence (T1/T2*w; 1.65 s temporal resolution). MRI was performed before and immediately after radiotherapy, at 3 months and at 1 year. Perfusion, blood volume, mean transit time, delay, dispersion, interstitial volume, and extraction coefficient were calculated in prostate cancer and normal prostate for all four time points using a sequential 3-compartment model. Results: Prostate cancer and normal prostate tissue showed a statistically significant decrease in perfusion (p = 0.006, p = 0.001) and increase in extraction coefficient (p = 0.004, p 3 min, p = 0.028) and a smaller extraction coefficient (0.42 vs. 0.64, p = 0.028). Conclusions: Two pharmacokinetic parameters, perfusion and extraction coefficient, appear to be suitable candidates for monitoring the response to percutaneous intensity-modulated radiotherapy of prostate cancer.

  16. The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non-metastatic prostate cancer: a validation study.

    Science.gov (United States)

    Gnanapragasam, V J; Bratt, O; Muir, K; Lee, L S; Huang, H H; Stattin, P; Lophatananon, A

    2018-02-28

    The purpose of this study is to validate a new five-tiered prognostic classification system to better discriminate cancer-specific mortality in men diagnosed with primary non-metastatic prostate cancer. We applied a recently described five-strata model, the Cambridge Prognostic Groups (CPGs 1-5), in two international cohorts and tested prognostic performance against the current standard three-strata classification of low-, intermediate- or high-risk disease. Diagnostic clinico-pathological data for men obtained from the Prostate Cancer data Base Sweden (PCBaSe) and the Singapore Health Study were used. The main outcome measure was prostate cancer mortality (PCM) stratified by age group and treatment modality. The PCBaSe cohort included 72,337 men, of whom 7162 died of prostate cancer. The CPG model successfully classified men with different risks of PCM with competing risk regression confirming significant intergroup distinction (p study of nearly 75,000 men confirms that the CPG five-tiered prognostic model has superior discrimination compared to the three-tiered model in predicting prostate cancer death across different age and treatment groups. Crucially, it identifies distinct sub-groups of men within the old intermediate-risk and high-risk criteria who have very different prognostic outcomes. We therefore propose adoption of the CPG model as a simple-to-use but more accurate prognostic stratification tool to help guide management for men with newly diagnosed prostate cancer.

  17. SU-F-BRD-01: A Logistic Regression Model to Predict Objective Function Weights in Prostate Cancer IMRT

    International Nuclear Information System (INIS)

    Boutilier, J; Chan, T; Lee, T; Craig, T; Sharpe, M

    2014-01-01

    Purpose: To develop a statistical model that predicts optimization objective function weights from patient geometry for intensity-modulation radiotherapy (IMRT) of prostate cancer. Methods: A previously developed inverse optimization method (IOM) is applied retrospectively to determine optimal weights for 51 treated patients. We use an overlap volume ratio (OVR) of bladder and rectum for different PTV expansions in order to quantify patient geometry in explanatory variables. Using the optimal weights as ground truth, we develop and train a logistic regression (LR) model to predict the rectum weight and thus the bladder weight. Post hoc, we fix the weights of the left femoral head, right femoral head, and an artificial structure that encourages conformity to the population average while normalizing the bladder and rectum weights accordingly. The population average of objective function weights is used for comparison. Results: The OVR at 0.7cm was found to be the most predictive of the rectum weights. The LR model performance is statistically significant when compared to the population average over a range of clinical metrics including bladder/rectum V53Gy, bladder/rectum V70Gy, and mean voxel dose to the bladder, rectum, CTV, and PTV. On average, the LR model predicted bladder and rectum weights that are both 63% closer to the optimal weights compared to the population average. The treatment plans resulting from the LR weights have, on average, a rectum V70Gy that is 35% closer to the clinical plan and a bladder V70Gy that is 43% closer. Similar results are seen for bladder V54Gy and rectum V54Gy. Conclusion: Statistical modelling from patient anatomy can be used to determine objective function weights in IMRT for prostate cancer. Our method allows the treatment planners to begin the personalization process from an informed starting point, which may lead to more consistent clinical plans and reduce overall planning time

  18. SU-F-BRD-01: A Logistic Regression Model to Predict Objective Function Weights in Prostate Cancer IMRT

    Energy Technology Data Exchange (ETDEWEB)

    Boutilier, J; Chan, T; Lee, T [University of Toronto, Toronto, Ontario (Canada); Craig, T; Sharpe, M [University of Toronto, Toronto, Ontario (Canada); The Princess Margaret Cancer Centre - UHN, Toronto, ON (Canada)

    2014-06-15

    Purpose: To develop a statistical model that predicts optimization objective function weights from patient geometry for intensity-modulation radiotherapy (IMRT) of prostate cancer. Methods: A previously developed inverse optimization method (IOM) is applied retrospectively to determine optimal weights for 51 treated patients. We use an overlap volume ratio (OVR) of bladder and rectum for different PTV expansions in order to quantify patient geometry in explanatory variables. Using the optimal weights as ground truth, we develop and train a logistic regression (LR) model to predict the rectum weight and thus the bladder weight. Post hoc, we fix the weights of the left femoral head, right femoral head, and an artificial structure that encourages conformity to the population average while normalizing the bladder and rectum weights accordingly. The population average of objective function weights is used for comparison. Results: The OVR at 0.7cm was found to be the most predictive of the rectum weights. The LR model performance is statistically significant when compared to the population average over a range of clinical metrics including bladder/rectum V53Gy, bladder/rectum V70Gy, and mean voxel dose to the bladder, rectum, CTV, and PTV. On average, the LR model predicted bladder and rectum weights that are both 63% closer to the optimal weights compared to the population average. The treatment plans resulting from the LR weights have, on average, a rectum V70Gy that is 35% closer to the clinical plan and a bladder V70Gy that is 43% closer. Similar results are seen for bladder V54Gy and rectum V54Gy. Conclusion: Statistical modelling from patient anatomy can be used to determine objective function weights in IMRT for prostate cancer. Our method allows the treatment planners to begin the personalization process from an informed starting point, which may lead to more consistent clinical plans and reduce overall planning time.

  19. Erratum: Epigenetic silencing of miR-34a in human prostate cancer cells and tumor tissue specimens can be reversed by BR-DIM treatment.

    Science.gov (United States)

    Kong, D; Heath, E; Chen, W; Cher, M; Powell, I; Heilbrun, L; Li, Y; Ali, S; Sethi, S; Hassan, O; Hwang, C; Gupta, N; Chitale, D; Sakr, Wa; Menon, M; Sarkar, Fh

    2013-01-01

    Androgen Receptor (AR) signaling is critically important during the development and progression of prostate cancer (PCa). The AR signaling is also important in the development of castrate resistant prostate cancer (CRPC) where AR is functional even after androgen deprivation therapy (ADT); however, little is known regarding the transcriptional and functional regulation of AR in PCa. Moreover, treatment options for primary PCa for preventing the occurrence of CRPC is limited; therefore, novel strategy for direct inactivation of AR is urgently needed. In this study, we found loss of miR-34a, which targets AR, in PCa tissue specimens, especially in patients with higher Gleason grade tumors, consistent with increased expression of AR. Forced over-expression of miR-34a in PCa cell lines led to decreased expression of AR and prostate specific antigen (PSA) as well as the expression of Notch-1, another important target of miR-34a. Most importantly, BR-DIM intervention in PCa patients prior to radical prostatectomy showed reexpression of miR-34a, which was consistent with decreased expression of AR, PSA and Notch-1 in PCa tissue specimens. Moreover, BR-DIM intervention led to nuclear exclusion both in PCa cell lines and in tumor tissues. PCa cells treated with BR-DIM and 5-aza-dC resulted in the demethylation of miR-34a promoter concomitant with inhibition of AR and PSA expression in LNCaP and C4-2B cells. These results suggest, for the first time, epigenetic silencing of miR-34a in PCa, which could be reversed by BR-DIM treatment and, thus BR-DIM could be useful for the inactivation of AR in the treatment of PCa.[This corrects the article on p. 14 in vol. 4.].

  20. A novel soft tissue prediction methodology for orthognathic surgery based on probabilistic finite element modelling.

    Science.gov (United States)

    Knoops, Paul G M; Borghi, Alessandro; Ruggiero, Federica; Badiali, Giovanni; Bianchi, Alberto; Marchetti, Claudio; Rodriguez-Florez, Naiara; Breakey, Richard W F; Jeelani, Owase; Dunaway, David J; Schievano, Silvia

    2018-01-01

    Repositioning of the maxilla in orthognathic surgery is carried out for functional and aesthetic purposes. Pre-surgical planning tools can predict 3D facial appearance by computing the response of the soft tissue to the changes to the underlying skeleton. The clinical use of commercial prediction software remains controversial, likely due to the deterministic nature of these computational predictions. A novel probabilistic finite element model (FEM) for the prediction of postoperative facial soft tissues is proposed in this paper. A probabilistic FEM was developed and validated on a cohort of eight patients who underwent maxillary repositioning and had pre- and postoperative cone beam computed tomography (CBCT) scans taken. Firstly, a variables correlation assessed various modelling parameters. Secondly, a design of experiments (DOE) provided a range of potential outcomes based on uniformly distributed input parameters, followed by an optimisation. Lastly, the second DOE iteration provided optimised predictions with a probability range. A range of 3D predictions was obtained using the probabilistic FEM and validated using reconstructed soft tissue surfaces from the postoperative CBCT data. The predictions in the nose and upper lip areas accurately include the true postoperative position, whereas the prediction under-estimates the position of the cheeks and lower lip. A probabilistic FEM has been developed and validated for the prediction of the facial appearance following orthognathic surgery. This method shows how inaccuracies in the modelling and uncertainties in executing surgical planning influence the soft tissue prediction and it provides a range of predictions including a minimum and maximum, which may be helpful for patients in understanding the impact of surgery on the face.

  1. Androgen receptor variant-7: an important predictive biomarker in castrate resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Oliver Sartor

    2015-06-01

    Full Text Available The recent manuscript in New England Journal of Medicine by Antonarakis et al. [1] has important clinical implications. This study evaluates mRNA expression of a particular androgen receptor splice variant-7 (AR-V7, in circulating tumor cells (CTCs from metastatic castrate-resistant prostate cancer (mCRPC patients receiving enzalutamide or abiraterone. The findings were striking, none of the 18 patients with detectable AR-V7 in CTCs had prostate-specific antigen (PSA responses. Further, the median time to PSA progression after enzalutamide or abiraterone treatment was only 1.3-1.4 months in AR-V7-positive patients as compared to 5.3-6.1 months in AR-V7 negative patients. AR-V7 in CTCs was also associated with shorter survival.

  2. ETS Gene Fusions as Predictive Biomarkers of Resistance to Radiation Therapy for Prostate Cancer

    Science.gov (United States)

    2016-05-01

    phenotype  in   preclinical  models  of  prostate  cancer,  2)  to  explore  the  mechanism  of  interaction  between   ERG  (the  predominant  ETS...established  this  axis  as  a  potential  therapeutic   target.         15. SUBJECT  TERMS Prostate cancer, ETS gene fusions, ERG , radiation resistance, DNA...interaction  between   ERG   (the   predominant   ETS   gene   fusion   product)   and   the   DNA   repair   protein   DNA-­PK,   and   3)   to

  3. Predicting volume of distribution with decision tree-based regression methods using predicted tissue:plasma partition coefficients.

    Science.gov (United States)

    Freitas, Alex A; Limbu, Kriti; Ghafourian, Taravat

    2015-01-01

    Volume of distribution is an important pharmacokinetic property that indicates the extent of a drug's distribution in the body tissues. This paper addresses the problem of how to estimate the apparent volume of distribution at steady state (Vss) of chemical compounds in the human body using decision tree-based regression methods from the area of data mining (or machine learning). Hence, the pros and cons of several different types of decision tree-based regression methods have been discussed. The regression methods predict Vss using, as predictive features, both the compounds' molecular descriptors and the compounds' tissue:plasma partition coefficients (Kt:p) - often used in physiologically-based pharmacokinetics. Therefore, this work has assessed whether the data mining-based prediction of Vss can be made more accurate by using as input not only the compounds' molecular descriptors but also (a subset of) their predicted Kt:p values. Comparison of the models that used only molecular descriptors, in particular, the Bagging decision tree (mean fold error of 2.33), with those employing predicted Kt:p values in addition to the molecular descriptors, such as the Bagging decision tree using adipose Kt:p (mean fold error of 2.29), indicated that the use of predicted Kt:p values as descriptors may be beneficial for accurate prediction of Vss using decision trees if prior feature selection is applied. Decision tree based models presented in this work have an accuracy that is reasonable and similar to the accuracy of reported Vss inter-species extrapolations in the literature. The estimation of Vss for new compounds in drug discovery will benefit from methods that are able to integrate large and varied sources of data and flexible non-linear data mining methods such as decision trees, which can produce interpretable models. Graphical AbstractDecision trees for the prediction of tissue partition coefficient and volume of distribution of drugs.

  4. Detection of AR-V7 mRNA in whole blood may not predict the effectiveness of novel endocrine drugs for castration-resistant prostate cancer.

    Science.gov (United States)

    Takeuchi, Takumi; Okuno, Yumiko; Hattori-Kato, Mami; Zaitsu, Masayoshi; Mikami, Koji

    2016-01-01

    A splice variant of androgen receptor (AR), AR-V7, lacks in androgen-binding portion and leads to aggressive cancer characteristics. Reverse transcription-polymerase chain reactions (PCRs) and subsequent nested PCRs for the amplification of AR-V7 and prostate-specific antigen (PSA) transcripts were done for whole blood of patients with prostate cancer and male controls. With primary reverse transcription PCRs, AR-V7 and PSA were detected in 4.5% and 4.7% of prostate cancer, respectively. With nested PCRs, AR-V7 messenger RNA (mRNA) was positive in 43.8% of castration-sensitive prostate cancer and 48.1% of castration-resistant prostate cancer (CRPC), while PSA mRNA was positive in 6.3% of castration-sensitive prostate cancer and 18.5% of CRPC. Whole-blood samples of controls showed AR-V7 mRNA expression by nested PCR. Based on multivariate analysis, expression of AR-V7 mRNA in whole blood was not significantly correlated with clinical parameters and PSA mRNA in blood, while univariate analysis showed a correlation between AR-V7 mRNA and metastasis at initial diagnosis. Detection of AR-V7 mRNA did not predict the reduction of serum PSA in patients with CRPC following abiraterone and enzalutamide administration. In conclusion, AR-V7 mRNA expression in normal hematopoietic cells may have annihilated the manifestation of aggressiveness of prostate cancer and the prediction of the effectiveness of abiraterone and enzalutamide by the assessment of AR-V7 mRNA in blood.

  5. Endosomal gene expression: a new indicator for prostate cancer patient prognosis?

    LENUS (Irish Health Repository)

    Johnson, Ian R D

    2015-11-10

    Prostate cancer continues to be a major cause of morbidity and mortality in men, but a method for accurate prognosis in these patients is yet to be developed. The recent discovery of altered endosomal biogenesis in prostate cancer has identified a fundamental change in the cell biology of this cancer, which holds great promise for the identification of novel biomarkers that can predict disease outcomes. Here we have identified significantly altered expression of endosomal genes in prostate cancer compared to non-malignant tissue in mRNA microarrays and confirmed these findings by qRT-PCR on fresh-frozen tissue. Importantly, we identified endosomal gene expression patterns that were predictive of patient outcomes. Two endosomal tri-gene signatures were identified from a previously published microarray cohort and had a significant capacity to stratify patient outcomes. The expression of APPL1, RAB5A, EEA1, PDCD6IP, NOX4 and SORT1 were altered in malignant patient tissue, when compared to indolent and normal prostate tissue. These findings support the initiation of a case-control study using larger cohorts of prostate tissue, with documented patient outcomes, to determine if different combinations of these new biomarkers can accurately predict disease status and clinical progression in prostate cancer patients.

  6. Lower-energy radiofrequency thermotherapy for benign prostatic hyperplasia. Prediction of a favorable treatment outcome

    International Nuclear Information System (INIS)

    Yanagisawa, Ryozo

    2007-01-01

    We evaluated short- and long-term results of lower-energy radiofrequency transurethral thermotherapy (TURT) for the treatment of benign prostatic hyperplasia and we investigated the predictors for a favorable treatment outcome. A total of 106 patients with benign prostatic hyperplasia underwent TURT, with TP10 used on 65 patients and Thermex I used on 41 patients. The assessment protocol consisted of international prostate symptom score (IPSS), quality of life (QOL) index, urodynamic study, dates of additional treatments and prostate examinations using transrectal ultrasonography and magnetic resonance imaging (MRI). Kaplan Meier survival analyses and logrank tests were used to assess an additional treatment-free period. At 3 months, the mean IPSS and QOL index had significantly decreased from 14.9 to 8.5 and from 4.2 to 2.5, respectively. Mean maximum flow rate had slightly but significantly increased from 11.4 to 11.9 ml per second. In accordance with guidelines proposed by the Japanese Urological Association, the overall clinical efficacy rate was 26.4%, including excellent, 7.5% and good, 18.9%. The efficacy rate was maintained for up to three years (29%) after the treatments in 31 patients who were able to be completely reevaluated. High IPSS and QOL index score were the predictors for short-term treatment outcome. Of the 106 patients, 76 were assessed by MRI before and 10 to 14 days after the treatment. The ranges of post-treatment-increased T2 signal were inversely associated with prostate volume. Kaplan Meier analysis indicated that 55% of the patients remained on TURT monotherapy five years after the treatment. Additional treatment-free periods were significantly longer in patients with an IPSS of 15 or less, with a QOL index of 4 or less, with a maximum flow rate of 10 ml per second or more, with a transition zone ratio of less than 0.4, or with a Schaefer obstruction grade of II or less at baseline. In conclusion, lower-energy radiofrequency

  7. Prostate positioning using cone-beam computer tomography based on manual soft-tissue registration. Interobserver agreement between radiation oncologists and therapists

    Energy Technology Data Exchange (ETDEWEB)

    Jereczek-Fossa, B.A.; Pobbiati, C.; Fanti, P. [European Institute of Oncology, Department of Radiation Oncology, Milan (Italy); University of Milan, Milan (Italy); Santoro, L. [European Institute of Oncology, Department of Epidemiology and Biostatistics, Milan (Italy); Fodor, C.; Zerini, D. [European Institute of Oncology, Department of Radiation Oncology, Milan (Italy); Vigorito, S. [European Institute of Oncology, Department of Medical Physics, Milan (Italy); Baroni, G. [Politecnico di Milano, Department of Electronics Information and Bioengineering, Milan (Italy); De Cobelli, O. [European Institute of Oncology, Department of Urology, Milan (Italy); University of Milan, Milan (Italy); Orecchia, R. [European Institute of Oncology, Department of Radiation Oncology, Milan (Italy); National Center for Oncological Hadrontherapy (CNAO) Foundation, Pavia (Italy); University of Milan, Milan (Italy)

    2014-01-15

    To check the interobserver agreement between radiation oncologists and therapists (RTT) using an on- and off-line cone-beam computer tomography (CBCT) protocol for setup verification in the radiotherapy of prostate cancer. The CBCT data from six prostate cancer patients treated with hypofractionated intensity-modulated radiotherapy (IMRT) were independently reviewed off-line by four observers (one radiation oncologist, one junior and two senior RTTs) and benchmarked with on-line CBCT positioning performed by a radiation oncologist immediately prior to treatment. CBCT positioning was based on manual soft-tissue registration. Agreement between observers was evaluated using weighted Cohen's kappa statistics. In total, 152 CBCT-based prostate positioning procedures were reviewed by each observer. The mean (± standard deviation) of the differences between off- and on-line CBCT-simCT registration translations along the three directions (antero-posterior, latero-lateral and cranio-caudal) and rotation around the antero-posterior axis were - 0.7 (3.6) mm, 1.9 (2.7) mm, 0.9 (3.6) mm and - 1.8 (5.0) degrees, respectively. Satisfactory interobserver agreement was found, being substantial (weighted kappa > 0.6) in 10 of 16 comparisons and moderate (0.41-0.60) in the remaining six comparisons. CBCT interpretation performed by RTTs is comparable to that of radiation oncologists. Our study might be helpful in the quality assurance of radiotherapy and the optimization of competencies. Further investigation should include larger sample sizes, a greater number of observers and validated methodology in order to assess interobserver variability and its impact on high-precision prostate cancer IGRT. In the future, it should enable the wider implementation of complex and evolving radiotherapy technologies. (orig.)

  8. Interpatient variation in normal peripheral zone apparent diffusion coefficient: effect on the prediction of prostate cancer aggressiveness

    NARCIS (Netherlands)

    Litjens, G.J.S.; Hambrock, T.; Hulsbergen-van de Kaa, C.A.; Barentsz, J.O.; Huisman, H.J.

    2012-01-01

    Purpose: To determine the interpatient variability of prostate peripheral zone (PZ) apparent diffusion coefficient (ADC) and its effect on the assessment of prostate cancer aggressiveness. Materials and Methods: The requirement for institutional review board approval was waived. Intra- and

  9. MALDI mass spectrometry based molecular phenotyping of CNS glial cells for prediction in mammalian brain tissue

    DEFF Research Database (Denmark)

    Hanrieder, Jørg; Wicher, Grzegorz; Bergquist, Jonas

    2011-01-01

    . Complementary proteomic experiments revealed the identity of these signature proteins that were predominantly expressed in the different glial cell types, including histone H4 for oligodendrocytes and S100-A10 for astrocytes. MALDI imaging MS was performed, and signature masses were employed as molecular...... tracers for prediction of oligodendroglial and astroglial localization in brain tissue. The different cell type specific protein distributions in tissue were validated using immunohistochemistry. ICMS of intact neuroglia is a simple and straightforward approach for characterization and discrimination...

  10. The value of endorectal MR imaging to predict positive biopsies in clinically intermediate-risk prostate cancer patients

    International Nuclear Information System (INIS)

    Vilanova, J.C.; Barcelo, J.; Comet, J.; Capdevila, A.; Dolz, J.L.; Huguet, M.; Aldoma, J.; Delgado, E.; Barcelo, C.

    2001-01-01

    The aim of this study was to assess the effectiveness of endorectal MR imaging in predicting the positive biopsy results in patients with clinically intermediate risk for prostate cancer. We performed a prospective endorectal MR imaging study with 81 patients at intermediate risk to detect prostate cancer between January 1997 and December 1998. Intermediate risk was defined as: prostatic specific antigen (PSA) levels between 4 and 10 ng/ml or PSA levels in the range of 10-20 ng/ml but negative digital rectal examination (DRE) or PSA levels progressively higher (0.75 ng/ml year -1 ). A transrectal sextant biopsy was performed after the endorectal MR exam, and also of the area of suspicion detected by MR imaging. The accuracies were measured, both singly for MR imaging and combined for PSA level and DRE, by calculating the area index of the receiver operating characteristics (ROC) curve. Cancer was detected in 23 patients (28 %). Overall sensitivity and specificity of endorectal MRI was 70 and 76 %, respectively. Accuracy was 71 % estimated from the area under the ROC curve for the total patient group and 84 % for the group of patients with PSA level between 10-20 ng/ml. Positive biopsy rate (PBR) was 63 % for the group with PSA 10-20 ng/ml and a positive MR imaging, and 15 % with a negative MR exam. The PBR was 43 % for the group with PSA 4-10 ng/ml and a positive MR study, and 13 % with a negative MR imaging examination. We would have avoided 63 % of negative biopsies, while missing 30 % of cancers for the total group of patients. Endorectal MR imaging was not a sufficient predictor of positive biopsies for patients clinically at intermediate risk for prostate cancer. Although we should not avoid performing systematic biopsies in patients with endorectal MR imaging negative results, as it will miss a significant number of cancers, selected patients with a PSA levels between 10-20 ng/ml or clinical-biopsy disagreement might benefit from endorectal MR imaging. (orig.)

  11. The value of endorectal MR imaging to predict positive biopsies in clinically intermediate-risk prostate cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Vilanova, J.C.; Barcelo, J. [Ressonancia Girona, Clinica Girona, Girona (Spain); Comet, J. [Dept. of Urology, Univ. Hospital of Girona (Spain); Capdevila, A.; Dolz, J.L.; Huguet, M.; Aldoma, J.; Delgado, E. [Centre Diagnostic Pedralbes, Cetir Grup Medic, Barcelona (Spain); Barcelo, C. [Dept. of Computer Science and Applied Mathematics, University of Girona (Spain)

    2001-02-01

    The aim of this study was to assess the effectiveness of endorectal MR imaging in predicting the positive biopsy results in patients with clinically intermediate risk for prostate cancer. We performed a prospective endorectal MR imaging study with 81 patients at intermediate risk to detect prostate cancer between January 1997 and December 1998. Intermediate risk was defined as: prostatic specific antigen (PSA) levels between 4 and 10 ng/ml or PSA levels in the range of 10-20 ng/ml but negative digital rectal examination (DRE) or PSA levels progressively higher (0.75 ng/ml year{sup -1}). A transrectal sextant biopsy was performed after the endorectal MR exam, and also of the area of suspicion detected by MR imaging. The accuracies were measured, both singly for MR imaging and combined for PSA level and DRE, by calculating the area index of the receiver operating characteristics (ROC) curve. Cancer was detected in 23 patients (28 %). Overall sensitivity and specificity of endorectal MRI was 70 and 76 %, respectively. Accuracy was 71 % estimated from the area under the ROC curve for the total patient group and 84 % for the group of patients with PSA level between 10-20 ng/ml. Positive biopsy rate (PBR) was 63 % for the group with PSA 10-20 ng/ml and a positive MR imaging, and 15 % with a negative MR exam. The PBR was 43 % for the group with PSA 4-10 ng/ml and a positive MR study, and 13 % with a negative MR imaging examination. We would have avoided 63 % of negative biopsies, while missing 30 % of cancers for the total group of patients. Endorectal MR imaging was not a sufficient predictor of positive biopsies for patients clinically at intermediate risk for prostate cancer. Although we should not avoid performing systematic biopsies in patients with endorectal MR imaging negative results, as it will miss a significant number of cancers, selected patients with a PSA levels between 10-20 ng/ml or clinical-biopsy disagreement might benefit from endorectal MR imaging

  12. Predicting Pathological Features at Radical Prostatectomy in Patients with Prostate Cancer Eligible for Active Surveillance by Multiparametric Magnetic Resonance Imaging.

    Directory of Open Access Journals (Sweden)

    Ottavio de Cobelli

    Full Text Available The aim of this study was to investigate the prognostic performance of multiparametric magnetic resonance imaging (mpMRI and Prostate Imaging Reporting and Data System (PIRADS score in predicting pathologic features in a cohort of patients eligible for active surveillance who underwent radical prostatectomy.A total of 223 patients who fulfilled the criteria for "Prostate Cancer Research International: Active Surveillance", were included. Mp-1.5 Tesla MRI examination staging with endorectal coil was performed at least 6-8 weeks after TRUS-guided biopsy. In all patients, the likelihood of the presence of cancer was assigned using PIRADS score between 1 and 5. Outcomes of interest were: Gleason score upgrading, extra capsular extension (ECE, unfavorable prognosis (occurrence of both upgrading and ECE, large tumor volume (≥ 0.5 ml, and seminal vesicle invasion (SVI. Receiver Operating Characteristic (ROC curves and Decision Curve Analyses (DCA were performed for models with and without inclusion of PIRADS score.Multivariate analysis demonstrated the association of PIRADS score with upgrading (P < 0.0001, ECE (P < 0.0001, unfavorable prognosis (P < 0.0001, and large tumor volume (P = 0.002. ROC curves and DCA showed that models including PIRADS score resulted in greater net benefit for almost all the outcomes of interest, with the only exception of SVI.mpMRI and PIRADS scoring are feasible tools in clinical setting and could be used as decision-support systems for a more accurate selection of patients eligible for AS.

  13. Simple Modification of the Bladder Outlet Obstruction Index for Better Prediction of Endoscopically-Proven Prostatic Obstruction: A Preliminary Study.

    Directory of Open Access Journals (Sweden)

    Jang Hee Han

    Full Text Available The bladder outlet obstruction index (BOOI, also known as the Abrams-Griffiths (AG number, is the most widely used index for predicting BOO. However, the obstructed prostatic urethra determined by the BOOI is often inconsistent with endoscopically-proven obstruction. We assessed abdominal straining pattern as a novel parameter for improving the prediction of BOO.We retrospectively reviewed the pressure-flow studies (PFS and cystourethroscopy in 176 BPH/LUTS patients who were unresponsive to medical therapy. During PFS, some groups of patients tried to urinate with abdominal straining, which can increases intravesical pressure and underestimate BOOI theoretically. Accordingly, the modified BOOI was defined as (PdetQmax+ΔPabd-2Qmax.Ultimately, 130 patients were eligible for the analysis. In PFS, ΔPabd (PabdQmax-initial Pabd was 11.81±13.04 cmH2O, and it was 0-9 cmH2O in 75 (57.7%, 10-19 cmH2O in 23 (17.7% and ≥20 cmH2O in 32 (24.6% patients. An endoscopically obstructed prostatic urethra in 92 patients was correctly determined in 47 patients (51.1% by the original BOOI versus 72 patients (78.3% based on the modified BOOI. Meanwhile, an "unobstructed" urethra according to the original BOOI was present in 11 patients (12.0%, whereas according to the modified BOOI, only 2 (2.1% would be labeled as "unobstructed". In receiver operating characteristic curves, the area under the curve was 0.906 using the modified BOOI number versus 0.849 in the original BOOI (p<0.05.The change in abdominal pressure was correlated with endoscopically-proven obstruction. Our simple modification of the BOOI on the basis of this finding better predicted bladder outlet obstruction and, therefore, should be considered when evaluating BOO in patients with LUTS/BPH.

  14. 1H magnetic resonance spectroscopy of the prostate

    International Nuclear Information System (INIS)

    Mueller-Lisse, U.G.; Scherr, M.

    2003-01-01

    To provide a brief summary of important technical and biochemical aspects and current clinical applications of magnetic resonance spectroscopy (MRS) of the prostate.Material and methods Pertinent radiological and biochemical literature was searched and retrieved via electronic media (medline trademark , pubmed trademark ). Basic concepts of MRS of the prostate and its clinical applications were extracted to provide an overview. The prostate lends itself to MRS due to its unique production, storage, and secretion of citrate. While healthy prostate tissue demonstrates high levels of citrate and low levels of choline that marks cell wall turnover, prostate cancer (PCA) utilizes citrate for energy metabolism and shows high levels of choline. The ratio of (choline + creatine)/citrate differentiates healthy prostate tissue and PCA. The combination of magnetic resonance imaging (MRI) and 3-dimensional MRS (3D-MRSI or 3D-CSI) of the prostate localizes PCA to a sextant of the peripheral zone of the prostate with sensitivity/specificity of up to 80/80%. Combined MRI and 3D-MRSI exceed the sensitivity and specificity of sextant biopsy of the prostate. When MRS and MRI agree on PCA presence, the positive predictive value is about 90%. In principle, combined MRI and 3D-MRSI recognize and localize remnant or recurrent cancer after hormone therapy, radiation therapy and cryo-surgery. Since it is non-invasive and radiation-free, combined MRI and 3D-MRSI lends itself to the planning of prostate biopsy and therapy as well as to post-therapeutic follow-up. For broad clinical application, it will be necessary to facilitate MRS examinations and their evaluation and make MRS available to a wider range of institutions. (orig.) [de

  15. Characterization of Prostate-Specific Membrane Antigen (PSMA) for Use in Therapeutic and Diagnostic Strategies Against Prostate Cancer

    National Research Council Canada - National Science Library

    O'Keefe, Denise

    2002-01-01

    Prostate-Specific Membrane Antigen (PSMA) appears to be an ideal prostate cancer marker and potential therapeutic target, however there have been reports of PSMA expression in non-prostatic tissues, including brain, kidney and liver...

  16. Genomic biomarkers of prenatal intrauterine inflammation in umbilical cord tissue predict later life neurological outcomes.

    Directory of Open Access Journals (Sweden)

    Sloane K Tilley

    Full Text Available Preterm birth is a major risk factor for neurodevelopmental delays and disorders. This study aimed to identify genomic biomarkers of intrauterine inflammation in umbilical cord tissue in preterm neonates that predict cognitive impairment at 10 years of age.Genome-wide messenger RNA (mRNA levels from umbilical cord tissue were obtained from 43 neonates born before 28 weeks of gestation. Genes that were differentially expressed across four indicators of intrauterine inflammation were identified and their functions examined. Exact logistic regression was used to test whether expression levels in umbilical cord tissue predicted neurocognitive function at 10 years of age.Placental indicators of inflammation were associated with changes in the mRNA expression of 445 genes in umbilical cord tissue. Transcripts with decreased expression showed significant enrichment for biological signaling processes related to neuronal development and growth. The altered expression of six genes was found to predict neurocognitive impairment when children were 10 years old These genes include two that encode for proteins involved in neuronal development.Prenatal intrauterine inflammation is associated with altered gene expression in umbilical cord tissue. A set of six of the differentially expressed genes predict cognitive impairment later in life, suggesting that the fetal environment is associated with significant adverse effects on neurodevelopment that persist into later childhood.

  17. Lesion volume predicts prostate cancer risk and aggressiveness: validation of its value alone and matched with prostate imaging reporting and data system score.

    Science.gov (United States)

    Martorana, Eugenio; Pirola, Giacomo Maria; Scialpi, Michele; Micali, Salvatore; Iseppi, Andrea; Bonetti, Luca Reggiani; Kaleci, Shaniko; Torricelli, Pietro; Bianchi, Giampaolo

    2017-07-01

    To demonstrate the association between magnetic resonance imaging (MRI) estimated lesion volume (LV), prostate cancer detection and tumour clinical significance, evaluating this variable alone and matched with Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score. We retrospectively analysed 157 consecutive patients, with at least one prior negative systematic prostatic biopsy, who underwent transperineal prostate MRI/ultrasonography fusion-targeted biopsy between January 2014 and February 2016. Suspicious lesions were delineated using a 'region of interest' and the system calculated prostate volume and LV. Patients were divided in groups considering LV (≤0.5, 0.5-1, ≥1 mL) and PI-RADS score (1-5). We considered clinically significant prostate cancer as all cancers with a Gleason score of ≥3 + 4 as suggested by PI-RADS v2. A direct comparison between MRI estimated LV (MRI LV) and histological tumour volume (HTV) was done in 23 patients who underwent radical prostatectomy during the study period. Differences between MRI LV and HTV were assessed using the paired sample t-test. MRI LV and HTV concordance was verified using a Bland-Altman plot. The chi-squared test and logistic and ordinal regression models were used to evaluate difference in frequencies. The MRI LV and PI-RADS score were associated both with prostate cancer detection (both P prostate cancer detection (P Prostate cancer detection was 1.4-times higher for LVs of 0.5-1 mL and 1.8-times higher for LVs of ≥1 mL; significant prostate cancer detection was 2.6-times for LVs of 0.5-1 mL and 4-times for LVs of ≥1 mL. There was a positive correlation between MRI LV and HTV (r = 0.9876, P prostate cancer detection and with tumour clinical significance. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

  18. Isotope and Patient Age Predict for PSA Spikes After Permanent Prostate Brachytherapy

    International Nuclear Information System (INIS)

    Bostancic, Chelsea; Merrick, Gregory S.; Butler, Wayne M.; Wallner, Kent E.; Allen, Zachariah; Galbreath, Robert; Lief, Jonathan; Gutman, Sarah E.

    2007-01-01

    Purpose: To evaluate prostate-specific antigen (PSA) spikes after permanent prostate brachytherapy in low-risk patients. Methods and Materials: The study population consisted of 164 prostate cancer patients who were part of a prospective randomized trial comparing 103 Pd and 125 I for low-risk disease. Of the 164 patients, 61 (37.2%) received short-course androgen deprivation therapy. The median follow-up was 5.4 years. On average, 11.1 post-treatment PSA measurements were obtained per patient. Biochemical disease-free survival was defined as a PSA level of ≤0.40 ng/mL after nadir. A PSA spike was defined as an increase of ≥0.2 ng/mL, followed by a durable decline to prespike levels. Multiple parameters were evaluated as predictors for a PSA spike. Results: Of the 164 patients, 44 (26.9%) developed a PSA spike. Of the 46 hormone-naive 125 I patients and 57 hormone-naive 103 Pd patients, 21 (45.7%) and 8 (14.0%) developed a PSA spike. In the hormone-naive patients, the mean time between implantation and the spike was 22.6 months and 18.7 months for 125 I and 103 Pd, respectively. In patients receiving neoadjuvant androgen deprivation therapy, the incidence of spikes was comparable between isotopes ( 125 I 28.1% and 103 Pd 20.7%). The incidence of spikes was substantially different in patients 125 I and/or <65 years of age. Differences in isotope-related spikes are most pronounced in hormone-naive patients

  19. Predictive Parameters of Symptomatic Hematochezia Following 5-Fraction Gantry-Based SABR in Prostate Cancer

    International Nuclear Information System (INIS)

    Musunuru, Hima Bindu; Davidson, Melanie; Cheung, Patrick; Vesprini, Danny; Liu, Stanley; Chung, Hans; Chu, William; Mamedov, Alexandre; Ravi, Ananth; D'Alimonte, Laura; Commisso, Kristina; Helou, Joelle; Deabreu, Andrea; Zhang, Liying; Loblaw, Andrew

    2016-01-01

    Purpose: This study identified predictors of high-grade late hematochezia (HH) following 5-fraction gantry-based stereotactic ablative radiation therapy (SABR). Methods and Materials: Hematochezia data for 258 patients who received 35 to 40 Gy SABR in 5-fractions as part of sequential phase 2 prospective trials was retrieved. Grade 2 or higher late rectal bleeding was labeled HH. Hematochezia needing steroid suppositories, 4% formalin, or 1 to 2 sessions of argon plasma coagulation (APC) was labeled grade 2. More than 2 sessions of APC, blood transfusion, or a course of hyperbaric oxygen was grade 3 and development of visceral fistula, grade 4. Various dosimetric and clinical factors were analyzed using univariate and multivariate analyses. Receiver operating characteristic (ROC) curve analysis and recursive partitioning analysis were used to determine clinically valid cut-off points and identify risk groups, respectively. Results: HH was observed in 19.4%, grade ≥3 toxicity in 3.1%. Median follow-up was 29.7 months (interquartile range [IQR]: 20.6-61.7) Median time to develop HH was 11.7 months (IQR: 9.0-15.2) from the start of radiation. At 2 years, cumulative HH was 4.9%, 27.2%, and 42.1% in patients who received 35 Gy to prostate (4-mm planning target volume [PTV] margin), 40 Gy to prostate (5-mm PTV margin), and 40 Gy to prostate/seminal vesicles (5-mm PTV margin), respectively (P 30%. Conclusions: Rectal V38 and 2 clinical factors were strong predictors of HH following 5-fraction SABR. Planning constraints should keep rectal V38 below 2.0 cm"3.

  20. Validity of a Manual Soft Tissue Profile Prediction Method Following Mandibular Setback Osteotomy

    OpenAIRE

    Kolokitha, Olga-Elpis

    2007-01-01

    Objectives The aim of this study was to determine the validity of a manual cephalometric method used for predicting the post-operative soft tissue profiles of patients who underwent mandibular setback surgery and compare it to a computerized cephalometric prediction method (Dentofacial Planner). Lateral cephalograms of 18 adults with mandibular prognathism taken at the end of pre-surgical orthodontics and approximately one year after surgery were used. Methods To test the validity of the manu...

  1. Tissue elasticity displayed by elastography and its correlation with the characteristics of collagen type I and type III in prostatic stroma

    Directory of Open Access Journals (Sweden)

    Jie Tang

    2014-04-01

    Full Text Available We investigated the prostate elasticity displayed by elastography and its correlation with the content and distribution of collagen type I (Col1 and type III (Col3. A total of 62 patients underwent transrectal real-time tissue elastography (TRTE examinations. Targeted biopsies were performed after 12-core systematic biopsy. The tissues corresponding to the elastograms were stained with picric acid-sirius red. The distribution of Col1 and type Col3 was observed, and the collagen volume fraction (CVF of these two types of collagen fibers was calculated. The CVFs of Col1 in the stiff and soft groups were 0.05 ± 0.02 and 0.02 ± 0.01 (P = 0.002, respectively. The CVFs of Col3 in the stiff and soft groups were 0.05 ± 0.04 and 0.07 ± 0.03 (P = 0.13, respectively. The circular analysis results showed that collagen fibers were disorganized both in the soft and stiff groups. Col1 and Col3 were mainly cross-linked, and some parallelization was observed in the sections. The distributions of Col1 and Col3 were different between the stiff and soft groups (P = 0.03. In conclusion, the texture of the prostate is due to the content of Col1 and its relative correlation with Col3.

  2. Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques

    Directory of Open Access Journals (Sweden)

    Bryan C. Au

    2016-02-01

    Full Text Available Anti-cancer immunotherapy is emerging from a nadir and demonstrating tangible benefits to patients. A variety of approaches are now employed. We are invoking antigen (Ag-specific responses through direct injections of recombinant lentivectors (LVs that encode sequences for tumor-associated antigens into multiple lymph nodes to optimize immune presentation/stimulation. Here we first demonstrate the effectiveness and antigen-specificity of this approach in mice challenged with prostate-specific antigen (PSA-expressing tumor cells. Next we tested the safety and efficacy of this approach in two cohorts of rhesus macaques as a prelude to a clinical trial application. Our vector encodes the cDNA for rhesus macaque PSA and a rhesus macaque cell surface marker to facilitate vector titering and tracking. We utilized two independent injection schemas demarcated by the timing of LV administration. In both cohorts we observed marked tissue-specific responses as measured by clinical evaluations and magnetic resonance imaging of the prostate gland. Tissue-specific responses were sustained for up to six months—the end-point of the study. Control animals immunized against an irrelevant Ag were unaffected. We did not observe vector spread in test or control animals or perturbations of systemic immune parameters. This approach thus offers an “off-the-shelf” anti-cancer vaccine that could be made at large scale and injected into patients—even on an out-patient basis.

  3. Nuclear androgen receptors in human prostatic tissue. Extraction with heparin and estimation of the number of binding sites with different methods

    International Nuclear Information System (INIS)

    Foekens, J.A.; Bolt-de Vries, J.; Mulder, E.; Blankenstein, M.A.; Schroeder, F.H.; Molen, H.J. van der

    1981-01-01

    A procedure for the estimation of nuclear androgen receptors in benign prostatic hyperplastic tissue is described, which employs extraction of receptors from nuclei with buffers containing heparin. Extraction of a nuclear pellet with a heparin-containing (1 g/l) buffer appeared to have definite advantages over 0.4 mol/l KCl extraction. Heparin appeared to be twice as efficient in extracting androgen receptors. In addition aggregated receptor proteins, formed after storage at -80 0 C, were partly deaggregated by heparin. Specific isolation of the androgen receptor was performed using either agar gel electrophoresis, protamine sulphate precipitation or LH-20 gel filtration. A comparison was made between the amounts of estimated receptors with these different techniques. Protamine sulphate precipitation resulted in the highest estimates of receptor-bound 5α-[ 3 H]dihydrotestosterone ( 3 H-DHT). Treatment of the labelled nuclear extracts with a charcoal suspension prior to the receptor assay resulted in lower amounts of estimated androgen receptors. A method for routine evaluation of nuclear androgen receptors in prostatic tissue has been evaluated, which involves extraction of nuclear pellets with a heparin-containing (1 g/l) buffer, exchange labelling of the nuclear extracts for 20 h at 10 0 C and quantification of the receptors with protamine sulphate precipitation. (Auth.)

  4. Tissue elasticity displayed by elastography and its correlation with the characteristics of collagen type I and type III in prostatic stroma.

    Science.gov (United States)

    Tang, Jie; Zhang, Yan; Zhang, Ming-Bo; Li, Yan-Mi; Fei, Xiang; Song, Zhi-Gang

    2014-01-01

    We investigated the prostate elasticity displayed by elastography and its correlation with the content and distribution of collagen type I (Col1) and type III (Col3). A total of 62 patients underwent transrectal real-time tissue elastography (TRTE) examinations. Targeted biopsies were performed after 12-core systematic biopsy. The tissues corresponding to the elastograms were stained with picric acid-sirius red. The distribution of Col1 and type Col3 was observed, and the collagen volume fraction (CVF) of these two types of collagen fibers was calculated. The CVFs of Col1 in the stiff and soft groups were 0.05 ± 0.02 and 0.02 ± 0.01 (P = 0.002), respectively. The CVFs of Col3 in the stiff and soft groups were 0.05 ± 0.04 and 0.07 ± 0.03 (P = 0.13), respectively. The circular analysis results showed that collagen fibers were disorganized both in the soft and stiff groups. Col1 and Col3 were mainly cross-linked, and some parallelization was observed in the sections. The distributions of Col1 and Col3 were different between the stiff and soft groups (P = 0.03). In conclusion, the texture of the prostate is due to the content of Col1 and its relative correlation with Col3.

  5. Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques.

    Science.gov (United States)

    Au, Bryan C; Lee, Chyan-Jang; Lopez-Perez, Orlay; Foltz, Warren; Felizardo, Tania C; Wang, James C M; Huang, Ju; Fan, Xin; Madden, Melissa; Goldstein, Alyssa; Jaffray, David A; Moloo, Badru; McCart, J Andrea; Medin, Jeffrey A

    2016-02-19

    Anti-cancer immunotherapy is emerging from a nadir and demonstrating tangible benefits to patients. A variety of approaches are now employed. We are invoking antigen (Ag)-specific responses through direct injections of recombinant lentivectors (LVs) that encode sequences for tumor-associated antigens into multiple lymph nodes to optimize immune presentation/stimulation. Here we first demonstrate the effectiveness and antigen-specificity of this approach in mice challenged with prostate-specific antigen (PSA)-expressing tumor cells. Next we tested the safety and efficacy of this approach in two cohorts of rhesus macaques as a prelude to a clinical trial application. Our vector encodes the cDNA for rhesus macaque PSA and a rhesus macaque cell surface marker to facilitate vector titering and tracking. We utilized two independent injection schemas demarcated by the timing of LV administration. In both cohorts we observed marked tissue-specific responses as measured by clinical evaluations and magnetic resonance imaging of the prostate gland. Tissue-specific responses were sustained for up to six months-the end-point of the study. Control animals immunized against an irrelevant Ag were unaffected. We did not observe vector spread in test or control animals or perturbations of systemic immune parameters. This approach thus offers an "off-the-shelf" anti-cancer vaccine that could be made at large scale and injected into patients-even on an out-patient basis.

  6. Bromodomain protein 4 discriminates tissue-specific super-enhancers containing disease-specific susceptibility loci in prostate and breast cancer

    DEFF Research Database (Denmark)

    Zuber, Verena; Bettella, Francesco; Witoelar, Aree

    2017-01-01

    progression. Although previous approaches have been tried to explain risk associated with SNPs in regulatory DNA elements, so far epigenetic readers such as bromodomain containing protein 4 (BRD4) and super-enhancers have not been used to annotate SNPs. In prostate cancer (PC), androgen receptor (AR) binding......Background: Epigenetic information can be used to identify clinically relevant genomic variants single nucleotide polymorphisms (SNPs) of functional importance in cancer development. Super-enhancers are cell-specific DNA elements, acting to determine tissue or cell identity and driving tumor...... the differential enrichment of SNPs mapping to specific categories of enhancers. We find that BRD4 is the key discriminant of tissue-specific enhancers, showing that it is more powerful than AR binding information to capture PC specific risk loci, and can be used with similar effect in breast cancer (BC...

  7. Three linked nomograms for predicting biochemical failure in prostate cancer treated with radiotherapy plus androgen deprivation therapy

    International Nuclear Information System (INIS)

    Lopez-Torrecilla, Jose; Boladeras, Anna; Angeles Cabeza, Maria; Zapatero, Almudena; Jove, Josep; Esteban, Luis M.; Henriquez, Ivan; Casana, Manuel; Mengual, Jose Luis; Gonzalez-San Segundo, Carmen; Gomez-Caamano, Antonio; Hervas, Asuncion; Munoz, Julia Luisa; Sanz, Gerardo

    2015-01-01

    Nomograms were established to predict biochemical recurrence (BCR) after radiotherapy (RT) with a low weight of the characteristic variables of RT and androgen deprivation therapy (ADT). Our aim is to provide a new stratified tool for predicting BCR at 4 and 7 years in patients treated using RT with radical intent. A retrospective, nonrandomized analysis was performed on 5044 prostate cancer (PCa) patients with median age 70 years, who received RT - with or without ADT - between November 1992 and May 2007. Median follow-up was 5.5 years. BCR was defined as a rise in serum prostate-specific antigen (PSA) of 2 ng/ml over the post-treatment PSA nadir. Univariate association between predictor variables and BCR was assessed by the log-rank test, and three linked nomograms were created for multivariate prognosis of BCR-free survival. Each nomogram corresponds to a category of the Gleason score - either 6,7, or 8-10 - and all of them were created from a single proportional hazards regression model stratified also by months of ADT (0, 1-6, 7-12, 13-24, 25-36, 36-60). The performance of this model was analyzed by calibration, discrimination, and clinical utility. Initial PSA, clinical stage, and RT dose were significant variables (p < 0.01). The model showed a good calibration. The concordance probability was 0.779, improving those obtained with other nomograms (0.587, 0.571, 0.554) in the database. Survival curves showed best clinical utility in a comparison with National Comprehensive Cancer Network (NCCN) risk groups. For each Gleason score category, the nomogram provides information on the benefit of adding ADT to a specific RT dose. (orig.) [de

  8. Predicting Classifier Performance with Limited Training Data: Applications to Computer-Aided Diagnosis in Breast and Prostate Cancer

    Science.gov (United States)

    Basavanhally, Ajay; Viswanath, Satish; Madabhushi, Anant

    2015-01-01

    Clinical trials increasingly employ medical imaging data in conjunction with supervised classifiers, where the latter require large amounts of training data to accurately model the system. Yet, a classifier selected at the start of the trial based on smaller and more accessible datasets may yield inaccurate and unstable classification performance. In this paper, we aim to address two common concerns in classifier selection for clinical trials: (1) predicting expected classifier performance for large datasets based on error rates calculated from smaller datasets and (2) the selection of appropriate classifiers based on expected performance for larger datasets. We present a framework for comparative evaluation of classifiers using only limited amounts of training data by using random repeated sampling (RRS) in conjunction with a cross-validation sampling strategy. Extrapolated error rates are subsequently validated via comparison with leave-one-out cross-validation performed on a larger dataset. The ability to predict error rates as dataset size increases is demonstrated on both synthetic data as well as three different computational imaging tasks: detecting cancerous image regions in prostate histopathology, differentiating high and low grade cancer in breast histopathology, and detecting cancerous metavoxels in prostate magnetic resonance spectroscopy. For each task, the relationships between 3 distinct classifiers (k-nearest neighbor, naive Bayes, Support Vector Machine) are explored. Further quantitative evaluation in terms of interquartile range (IQR) suggests that our approach consistently yields error rates with lower variability (mean IQRs of 0.0070, 0.0127, and 0.0140) than a traditional RRS approach (mean IQRs of 0.0297, 0.0779, and 0.305) that does not employ cross-validation sampling for all three datasets. PMID:25993029

  9. The Cancer of the Prostate Risk Assessment (CAPRA) score predicts biochemical recurrence in intermediate-risk prostate cancer treated with external beam radiotherapy (EBRT) dose escalation or low-dose rate (LDR) brachytherapy.

    Science.gov (United States)

    Krishnan, Vimal; Delouya, Guila; Bahary, Jean-Paul; Larrivée, Sandra; Taussky, Daniel

    2014-12-01

    To study the prognostic value of the University of California, San Francisco Cancer of the Prostate Risk Assessment (CAPRA) score to predict biochemical failure (bF) after various doses of external beam radiotherapy (EBRT) and/or permanent seed low-dose rate (LDR) prostate brachytherapy (PB). We retrospectively analysed 345 patients with intermediate-risk prostate cancer, with PSA levels of 10-20 ng/mL and/or Gleason 7 including 244 EBRT patients (70.2-79.2 Gy) and 101 patients treated with LDR PB. The minimum follow-up was 3 years. No patient received primary androgen-deprivation therapy. bF was defined according to the Phoenix definition. Cox regression analysis was used to estimate the differences between CAPRA groups. The overall bF rate was 13% (45/345). The CAPRA score, as a continuous variable, was statistically significant in multivariate analysis for predicting bF (hazard ratio [HR] 1.37, 95% confidence interval [CI] 1.10-1.72, P = 0.006). There was a trend for a lower bF rate in patients treated with LDR PB when compared with those treated by EBRT ≤ 74 Gy (HR 0.234, 95% CI 0.05-1.03, P = 0.055) in multivariate analysis. In the subgroup of patients with a CAPRA score of 3-5, CAPRA remained predictive of bF as a continuous variable (HR 1.51, 95% CI 1.01-2.27, P = 0.047) in multivariate analysis. The CAPRA score is useful for predicting biochemical recurrence in patients treated for intermediate-risk prostate cancer with EBRT or LDR PB. It could help in treatment decisions. © 2013 The Authors. BJU International © 2013 BJU International.

  10. Prostate Ultrasound

    Medline Plus

    Full Text Available ... ultrasound or with a rectal examination, an ultrasound-guided biopsy can be performed. This procedure involves advancing ... of the Prostate) Prostate Cancer Ultrasound- and MRI-Guided Prostate Biopsy Images related to Ultrasound - Prostate Sponsored ...

  11. Prostate Ultrasound

    Medline Plus

    Full Text Available ... is enlarged, also known as benign prostatic hyperplasia (BPH) , with measurements acquired as needed for any treatment ... caption Related Articles and Media Benign Prostatic Hyperplasia (BPH) (Enlargement of the Prostate) Prostate Cancer Ultrasound- and ...

  12. The epigenetic promise for prostate cancer diagnosis.

    Science.gov (United States)

    Van Neste, Leander; Herman, James G; Otto, Gaëtan; Bigley, Joseph W; Epstein, Jonathan I; Van Criekinge, Wim

    2012-08-01

    Prostate cancer is the most common cancer diagnosis in men and a leading cause of death. Improvements in disease management would have a significant impact and could be facilitated by the development of biomarkers, whether for diagnostic, prognostic, or predictive purposes. The blood-based prostate biomarker PSA has been part of clinical practice for over two decades, although it is surrounded by controversy. While debates of usefulness are ongoing, alternatives should be explored. Particularly with recent recommendations against routine PSA-testing, the time is ripe to explore promising biomarkers to yield a more efficient and accurate screening for detection and management of prostate cancer. Epigenetic changes, more specifically DNA methylation, are amongst the most common alterations in human cancer. These changes are associated with transcriptional silencing of genes, leading to an altered cellular biology. One gene in particular, GSTP1, has been widely studied in prostate cancer. Therefore a meta-analysis has been conducted to examine the role of this and other genes and the potential contribution to prostate cancer management and screening refinement. More than 30 independent, peer reviewed studies have reported a consistently high sensitivity and specificity of GSTP1 hypermethylation in prostatectomy or biopsy tissue. The meta-analysis combined and compared these results. GSTP1 methylation detection can serve an important role in prostate cancer managment. The meta-analysis clearly confirmed a link between tissue DNA hypermethylation of this and other genes and prostate cancer. Detection of DNA methylation in genes, including GSTP1, could serve an important role in clinical practice. Copyright © 2011 Wiley Periodicals, Inc.

  13. Strain Elastography for Prediction of Malignancy in Soft Tissue Tumours--Preliminary Results

    DEFF Research Database (Denmark)

    Riishede, I; Ewertsen, C; Carlsen, J

    2015-01-01

    PURPOSE: To evaluate the ability of strain elastography to predict malignancy in patients with soft tissue tumors, and to compare three evaluation methods of strain elastography: strain ratios, strain histograms and visual scoring. MATERIALS AND METHODS: 60 patients with 61 tumors were analyzed...

  14. Amyloid Load in Fat Tissue Reflects Disease Severity and Predicts Survival in Amyloidosis

    NARCIS (Netherlands)

    Van Gameren, Ingrid I.; Hazenberg, Bouke P. C.; Bijzet, Johan; Haagsma, Elizabeth B.; Vellenga, Edo; Posthumus, Marcel D.; Jager, Pieter L.; Van Rijswijk, Martin H.

    Objective. The severity of systemic amyloidosis is thought to be related to the extent of amyloid deposition. We studied whether amyloid load in fat tissue reflects disease severity and predicts survival. Methods. We studied all consecutive patients with systemic amyloidosis seen between January

  15. Artificial neural network prediction of ischemic tissue fate in acute stroke imaging

    Science.gov (United States)

    Huang, Shiliang; Shen, Qiang; Duong, Timothy Q

    2010-01-01

    Multimodal magnetic resonance imaging of acute stroke provides predictive value that can be used to guide stroke therapy. A flexible artificial neural network (ANN) algorithm was developed and applied to predict ischemic tissue fate on three stroke groups: 30-, 60-minute, and permanent middle cerebral artery occlusion in rats. Cerebral blood flow (CBF), apparent diffusion coefficient (ADC), and spin–spin relaxation time constant (T2) were acquired during the acute phase up to 3 hours and again at 24 hours followed by histology. Infarct was predicted on a pixel-by-pixel basis using only acute (30-minute) stroke data. In addition, neighboring pixel information and infarction incidence were also incorporated into the ANN model to improve prediction accuracy. Receiver-operating characteristic analysis was used to quantify prediction accuracy. The major findings were the following: (1) CBF alone poorly predicted the final infarct across three experimental groups; (2) ADC alone adequately predicted the infarct; (3) CBF+ADC improved the prediction accuracy; (4) inclusion of neighboring pixel information and infarction incidence further improved the prediction accuracy; and (5) prediction was more accurate for permanent occlusion, followed by 60- and 30-minute occlusion. The ANN predictive model could thus provide a flexible and objective framework for clinicians to evaluate stroke treatment options on an individual patient basis. PMID:20424631

  16. Validity of a manual soft tissue profile prediction method following mandibular setback osteotomy.

    Science.gov (United States)

    Kolokitha, Olga-Elpis

    2007-10-01

    The aim of this study was to determine the validity of a manual cephalometric method used for predicting the post-operative soft tissue profiles of patients who underwent mandibular setback surgery and compare it to a computerized cephalometric prediction method (Dentofacial Planner). Lateral cephalograms of 18 adults with mandibular prognathism taken at the end of pre-surgical orthodontics and approximately one year after surgery were used. To test the validity of the manual method the prediction tracings were compared to the actual post-operative tracings. The Dentofacial Planner software was used to develop the computerized post-surgical prediction tracings. Both manual and computerized prediction printouts were analyzed by using the cephalometric system PORDIOS. Statistical analysis was performed by means of t-test. Comparison between manual prediction tracings and the actual post-operative profile showed that the manual method results in more convex soft tissue profiles; the upper lip was found in a more prominent position, upper lip thickness was increased and, the mandible and lower lip were found in a less posterior position than that of the actual profiles. Comparison between computerized and manual prediction methods showed that in the manual method upper lip thickness was increased, the upper lip was found in a more anterior position and the lower anterior facial height was increased as compared to the computerized prediction method. Cephalometric simulation of post-operative soft tissue profile following orthodontic-surgical management of mandibular prognathism imposes certain limitations related to the methods implied. However, both manual and computerized prediction methods remain a useful tool for patient communication.

  17. Impact of the integration of proton magnetic resonance imaging spectroscopy to PI-RADS 2 for prediction of high grade and high stage prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Leapman, Michael S.; Wang, Zhen J.; Behr, Spencer C.; Kurhanewicz, John; Zagoria, Ronald J.; Carroll, Peter R.; Westphalen, Antonio C., E-mail: antonio.westphalen@ucsf.edu [University of California, San Francisco, CA (United States)

    2017-09-15

    Objective: To compare the predictions of dominant Gleason pattern ≥ 4 or non-organ confined disease with Prostate Imaging Reporting and Data System (PI-RADS v2) with or without proton magnetic resonance spectroscopic imaging ({sup 1}H-MRSI). Materials and Methods: Thirty-nine men underwent 3-tesla endorectal multiparametric MRI including {sup 1}H-MRSI and prostatectomy. Two radiologists assigned PI-RADS v2 and {sup 1}H-MRSI scores to index lesions. Statistical analyses used logistic regressions, receiver operating characteristic (ROC) curves, and 2 x 2 tables for diagnostic accuracies. Results: The sensitivity and specificity of {sup 1}H-MRSI and PI-RADS v2 for high-grade prostate cancer (PCa) were 85.7% (57.1%) and 92.9% (100%), and 56% (68.0%) and 24.0% (24.0%). The sensitivity and specificity of {sup 1}H-MRSI and PI-RADS v2 for extra-prostatic extension (EPE) were 64.0% (40%) and 20.0% (48%), and 50.0% (57.1%) and 71.4% (64.3%). The area under the ROC curves (AUC) for prediction of high-grade prostate cancer were 0.65 and 0.61 for PI-RADS v2 and 0.72 and 0.70 when combined with {sup 1}H-MRSI (readers 1 and 2, p = 0.04 and 0.21). For prediction of EPE the AUC were 0.54 and 0.60 for PI-RADS v2 and 0.55 and 0.61 when combined with {sup 1}H-MRSI (p > 0.05). Conclusion: {sup 1}H-MRSI might improve the discrimination of high-grade prostate cancer when combined to PI-RADS v2, particularly for PI-RADS v2 score 4 lesions, but it does not affect the prediction of EPE. (author)

  18. Impact of the integration of proton magnetic resonance imaging spectroscopy to PI-RADS 2 for prediction of high grade and high stage prostate cancer

    International Nuclear Information System (INIS)

    Leapman, Michael S.; Wang, Zhen J.; Behr, Spencer C.; Kurhanewicz, John; Zagoria, Ronald J.; Carroll, Peter R.; Westphalen, Antonio C.

    2017-01-01

    Objective: To compare the predictions of dominant Gleason pattern ≥ 4 or non-organ confined disease with Prostate Imaging Reporting and Data System (PI-RADS v2) with or without proton magnetic resonance spectroscopic imaging ("1H-MRSI). Materials and Methods: Thirty-nine men underwent 3-tesla endorectal multiparametric MRI including "1H-MRSI and prostatectomy. Two radiologists assigned PI-RADS v2 and "1H-MRSI scores to index lesions. Statistical analyses used logistic regressions, receiver operating characteristic (ROC) curves, and 2 x 2 tables for diagnostic accuracies. Results: The sensitivity and specificity of "1H-MRSI and PI-RADS v2 for high-grade prostate cancer (PCa) were 85.7% (57.1%) and 92.9% (100%), and 56% (68.0%) and 24.0% (24.0%). The sensitivity and specificity of "1H-MRSI and PI-RADS v2 for extra-prostatic extension (EPE) were 64.0% (40%) and 20.0% (48%), and 50.0% (57.1%) and 71.4% (64.3%). The area under the ROC curves (AUC) for prediction of high-grade prostate cancer were 0.65 and 0.61 for PI-RADS v2 and 0.72 and 0.70 when combined with "1H-MRSI (readers 1 and 2, p = 0.04 and 0.21). For prediction of EPE the AUC were 0.54 and 0.60 for PI-RADS v2 and 0.55 and 0.61 when combined with "1H-MRSI (p > 0.05). Conclusion: "1H-MRSI might improve the discrimination of high-grade prostate cancer when combined to PI-RADS v2, particularly for PI-RADS v2 score 4 lesions, but it does not affect the prediction of EPE. (author)

  19. Predictive Parameters of Symptomatic Hematochezia Following 5-Fraction Gantry-Based SABR in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Musunuru, Hima Bindu [Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Davidson, Melanie [Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Department of Medical Physics, Odette Cancer Centre, Toronto, Ontario (Canada); Cheung, Patrick; Vesprini, Danny; Liu, Stanley; Chung, Hans; Chu, William [Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Mamedov, Alexandre [Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Ravi, Ananth [Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Department of Medical Physics, Odette Cancer Centre, Toronto, Ontario (Canada); D' Alimonte, Laura [Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Commisso, Kristina [Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Helou, Joelle [Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Deabreu, Andrea [Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Zhang, Liying [MacroStat, Inc, Toronto, Ontario (Canada); Loblaw, Andrew, E-mail: andrew.loblaw@sunnybrook.ca [Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Department of Health Policy, Measurement and Evaluation, University of Toronto, Toronto, Ontario (Canada)

    2016-04-01

    Purpose: This study identified predictors of high-grade late hematochezia (HH) following 5-fraction gantry-based stereotactic ablative radiation therapy (SABR). Methods and Materials: Hematochezia data for 258 patients who received 35 to 40 Gy SABR in 5-fractions as part of sequential phase 2 prospective trials was retrieved. Grade 2 or higher late rectal bleeding was labeled HH. Hematochezia needing steroid suppositories, 4% formalin, or 1 to 2 sessions of argon plasma coagulation (APC) was labeled grade 2. More than 2 sessions of APC, blood transfusion, or a course of hyperbaric oxygen was grade 3 and development of visceral fistula, grade 4. Various dosimetric and clinical factors were analyzed using univariate and multivariate analyses. Receiver operating characteristic (ROC) curve analysis and recursive partitioning analysis were used to determine clinically valid cut-off points and identify risk groups, respectively. Results: HH was observed in 19.4%, grade ≥3 toxicity in 3.1%. Median follow-up was 29.7 months (interquartile range [IQR]: 20.6-61.7) Median time to develop HH was 11.7 months (IQR: 9.0-15.2) from the start of radiation. At 2 years, cumulative HH was 4.9%, 27.2%, and 42.1% in patients who received 35 Gy to prostate (4-mm planning target volume [PTV] margin), 40 Gy to prostate (5-mm PTV margin), and 40 Gy to prostate/seminal vesicles (5-mm PTV margin), respectively (P<.0001). In the ROC analysis, volume of rectum receiving radiation dose of 38 Gy (V38) was a strong predictor of HH with an area under the curve of 0.65. In multivariate analysis, rectal V38 (≥2.0 cm{sup 3}; odds ratio [OR]: 4.7); use of anticoagulants in the follow-up period (OR: 6.5) and presence of hemorrhoids (OR: 2.7) were the strongest predictors. Recursive partitioning analysis showed rectal V38 < 2.0 cm{sup 3}, and use of anticoagulants or rectal V38 ≥ 2.0 cm{sup 3} plus 1 other risk factor resulted in an HH risk of >30%. Conclusions: Rectal V38 and 2

  20. Prevalence and Predicting Factors for Commonly Neglected Sexual Side Effects to External-Beam Radiation Therapy for Prostate Cancer.

    Science.gov (United States)

    Frey, Anders; Pedersen, Christian; Lindberg, Henriette; Bisbjerg, Rasmus; Sønksen, Jens; Fode, Mikkel

    2017-04-01

    pursue. Frey A, Pedersen C, Lindberg H, et al. Prevalence and Predicting Factors for Commonly Neglected Sexual Side Effects to External-Beam Radiation Therapy for Prostate Cancer. J Sex Med 2017;14:558-565. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  1. Induced Chronic Prostatitis in Rats

    African Journals Online (AJOL)

    Similarly, compared with reference group (176.1 ± 12.1 pg/ml), IL-1β level of prostate tissues of high-dose PCS ..... Fig 1: Effect of PCS extract on the histomorphology of prostate tissues in rats. ... involved with cellular recruitment, fever, acute.

  2. Dietary Phytoestrogens and Prostate Cancer Prevention

    National Research Council Canada - National Science Library

    Kurzer, Mindy S; Slaton, Joel

    2007-01-01

    The main objective of this project is to evaluate the effects of soy phytoestrogens on reproductive hormones and prostate tissue markers of cell proliferation and androgen action in men at high risk of prostate cancer...

  3. Nomogram incorporating PSA level to predict cancer-specific survival for men with clinically localized prostate cancer managed without curative intent

    Science.gov (United States)

    Kattan, Michael W.; Cuzick, Jack; Fisher, Gabrielle; Berney, Daniel M.; Oliver, Tim; Foster, Christopher S.; Møller, Henrik; Reuter, Victor; Fearn, Paul; Eastham, James; Scardino, Peter T.

    2012-01-01

    Introduction The prognosis of men with clinically localized prostate cancer is highly variable, and it is difficult to counsel a man who may be considering avoiding, or delaying, aggressive therapy. After collecting data on a large cohort of men who received no initial active prostate cancer therapy, we sought to develop, and to internally validate, a nomogram for prediction of disease-specific survival. Methods Working with 6 cancer registries within England and numerous hospitals in the region, we constructed a population-based cohort of men diagnosed with prostate cancer between 1990 and 1996. All men had baseline serum prostate specific antigen (PSA) measurements, centralized pathologic grading, and centralized review of clinical stage assignment. Based upon the clinical and pathological data from 1,911 men, we developed and validated a statistical model that served as the basis for the nomogram. The discrimination and calibration of the nomogram were assessed with use of one third of the men, who were omitted from modeling and used as a test sample. Results The median age of the included men was 70.4 years. The 25th and 75th percentiles of PSA were 7.3 and 32.6 ng/ml respectively, and the median was 15.4 ng/ml. Forty-two percent of the men had high grade disease. The nomogram predicted well with a concordance index of 0.73 and had good calibration. Conclusions We have developed an accurate tool for predicting the probability that a man with clinically localized prostate cancer will survive his disease for 120 months if the cancer is not treated with curative intent immediately. The tool should be helpful for patient counseling and clinical trial design. PMID:18000803

  4. Decreased expression of caspase3 in penis and prostate tissues of rat after the treatment with buceng (Pimpinella alpina Molk & Euricoma longifolia Jack

    Directory of Open Access Journals (Sweden)

    Taufiqurrachman Taufiqurrachman

    2013-02-01

    Full Text Available Background: Buceng {combination of pasak bumi (Eurycoma longifolia Jack and purwoceng (Pimpinella alpine Molk} has been proven to increase testosterone (Te level and decrease apoptosis. Unfortunately, there is no evidence whether these effects are mediated by the declining of caspase3. Objective of this study was to evaluate whether buceng could decrease the expression of caspase3 of penis and prostate cells in Sprague Dawley male rats.Methods: Twenty four Sprague Dawley male rats weighing 300 g (90 days old were randomly assigned into 4 groups of 6 male rats. Group A, rats were castrated and received buceng 50 mg. Group B, rats were not castrated, sacrifices as positive control. Group C, rats were castrated and given 2 mL aquadest as negative control. Group D, rats were castrated and got of 6.75 mg mesterolone, dissolved in 2 mL water. MANOVA statistical analysis was adopted to examine the difference expression of caspase3 in all groups. The comparison of caspase3 expression between two groups exhibiting difference values were evaluated by Post Hoc test.Results: MANOVA revealed statistically significant differences in the expression of caspase3 of penis and prostate tissues among the four groups. Post Hoct test also indicated that expression of caspase3 in group A (buceng (33.56; 35.83 was significantly lower compared to group C (negative control (54.33; 60.07 and group D (mesterolone (51.91;56.21, p = 0.000, and higher compared than group B or normal rats (29.40; 27.72, but statistically not significant (p = 0.826.Conclusion: The treatment of 50 mg buceng/day for 30 consecutive days could decrease caspase3 expression in penis and prostate cells. (Med J Indones. 2013;22:2-8Keywords: Apoptosis, buceng (Pimpinella alpine Molk – Eurycoma longifolia Jack, caspase3 

  5. Expression of urokinase plasminogen activator, its receptor and type-1 inhibitor in malignant and benign prostate tissue

    DEFF Research Database (Denmark)

    Usher, Pernille Autzen; Thomsen, Ole Frøkjær; Iversen, Peter

    2005-01-01

    The plasminogen activation (PA) cascade participates in degradation of extracellular matrix during cancer invasion. We have studied the expression of urokinase-type plasminogen activator (uPA) mRNA, uPA receptor (uPAR) mRNA and immunoreactivity, and type-1 plasminogen activator inhibitor (PAI-1) m......RNA and immunoreactivity in 16 prostate adenocarcinomas and 9 benign prostate hyperplasias. uPA mRNA and uPAR mRNA expression were found in 9 and 8 of the adenocarcinomas, respectively, and in 7 and 6 of the benign hyperplasias, respectively. In both malignant and benign lesions, expression of these 2 m...... proximity to cancer cell islands. No immunoreactivity and/or mRNA expression of uPA, uPAR or PAI-1 was observed in cancer cells or in other epithelial cells in any of the cases....

  6. [Expressions of interleukin-17 and interleukin-8 in the prostatic tissue of the patients with BPH or BPH with inflammation].

    Science.gov (United States)

    Gao, Rui; Liu, Qi-Xiang; Zhou, Hui-Liang; Cao, Lin-Sheng; Jiang, Tao; Tang, Song-Xi; Ding, Yi-Lang

    2017-08-01

    To investigate the expressions of interleukin-17 (IL-17) and interleukin-8 (IL-8) in benign prostatic hyperplasia (BPH) and BPH complicated with histological inflammation and their significance. According to the results of HE staining, we divided 60 cases of BPH treated by transurethral resection of the prostate (TURP) into a BPH group (n = 23) and a BPH with inflammation group (n = 37). We analyzed the clinical data of the patients and determined the mRNA and protein expressions of IL-17 and IL-8 by immunohistochemistry, real-time fluorescence quantitative PCR, and Western blot, respectively. Compared with the BPH patients complicated with inflammation, the BPH group showed significantly lower International Prostate Symptom Score (IPSS) (29.1 ± 6.2 vs 21.6 ± 3.7), quality of life score (QoL) (5.4 ± 1.3 vs 4.4 ± 1.6), postvoid residual urine volume (RUV) ([198.6 ± 15.5] vs [98.2 ± 19.3] ml), prostate volume ([69.2 ± 24.1] vs [49.8 ± 16.5] ml), PSA level ([7.4 ± 1.9] vs [2.8 ± 0.8] μg/L) and serum c-reactive protein content (CRP) ([5.1±2.0] vs [1.5±0.6] mg/L), but a higher maximum urine flow rate (Qmax) ([4.7 ± 2.1] vs [8.2 ± 1.8] ml/s) (all PBPH patients with inflammation, which may play a significant role in the development and progression of BPH.

  7. Evaluating the Potential of Adipose Tissue-Derived MSCs as Anticancer Gene Delivery Vehicles to Bone-Metastasized Prostate Cancer

    Science.gov (United States)

    2010-04-01

    cells may allow red-ox pathways to be used for mitogenic purposes. These cells also overexpress the antioxidant proteins, Thioredoxin-1 ( Trx -1) and...shown to modify hormone receptor signaling in both breast and prostate cancer. Trx - 1 can differentially modulate estrogen receptor (ER) signaling in...of AR dependent PCa cell growth may be achieved by suppressing the induction of Prx-1 and Trx -1. Induction of these antioxidant proteins are

  8. Tissue Biomarkers in Predicting Response to Sunitinib Treatment of Metastatic Renal Cell Carcinoma.

    Science.gov (United States)

    Trávníček, Ivan; Branžovský, Jindřich; Kalusová, Kristýna; Hes, Ondřej; Holubec, Luboš; Pele, Kevin Bauleth; Ürge, Tomáš; Hora, Milan

    2015-10-01

    To identify tissue biomarkers that are predictive of the therapeutic effect of sunitinib in treatment of metastatic clear cell renal cell carcinoma (mCRCC). Our study included 39 patients with mCRCC treated with sunitinib. Patients were stratified into two groups based on their response to sunitinib treatment: non-responders (progression), and responders (stable disease, regression). The effect of treatment was measured by comparing imaging studies before the initiation treatment with those performed at between 3rd and 7th months of treatment, depending on the patient. Histological samples of tumor tissue and healthy renal parenchyma, acquired during surgery of the primary tumor, were examined with immunohistochemistry to detect tissue targets involved in the signaling pathways of tumor growth and neoangiogenesis. We selected mammalian target of rapamycine, p53, vascular endothelial growth factor, hypoxia-inducible factor 1 and 2 and carbonic anhydrase IX. We compared the average levels of biomarker expression in both, tumor tissue, as well as in healthy renal parenchyma. Results were evaluated using the Student's t-test. For responders, statistically significant differences in marker expression in tumor tissue versus healthy parenchyma were found for mTOR (4%/16.7%; p=0.01031), p53 (4%/12.7%; p=0.042019), VEGF (62.7%/45%; p=0.019836) and CAIX (45%/15.33%; p=0.001624). A further significant difference was found in the frequency of high expression (more than 60%) between tumor tissue and healthy parenchyma in VEGF (65%/35%; p=0.026487) and CAIX (42%/8%; p=0.003328). CAIX was expressed at high levels in the tumor tissue in both evaluated groups. A significantly higher expression of VEGF in CRCC in comparison to healthy parenchyma can predict a better response to sunitinib. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  9. Improved tissue assignment using dual-energy computed tomography in low-dose rate prostate brachytherapy for Monte Carlo dose calculation

    Energy Technology Data Exchange (ETDEWEB)

    Côté, Nicolas [Département de Physique, Université de Montréal, Pavillon Roger-Gaudry (D-428), 2900 Boulevard Édouard-Montpetit, Montréal, Québec H3T 1J4 (Canada); Bedwani, Stéphane [Département de Radio-Oncologie, Centre Hospitalier de l’Université de Montréal (CHUM), 1560 Rue Sherbrooke Est, Montréal, Québec H2L 4M1 (Canada); Carrier, Jean-François, E-mail: jean-francois.carrier.chum@ssss.gouv.qc.ca [Département de Physique, Université de Montréal, Pavillon Roger-Gaudry (D-428), 2900 Boulevard Édouard-Montpetit, Montréal, Québec H3T 1J4, Canada and Département de Radio-Oncologie, Centre Hospitalier de l’Université de Montréal (CHUM), 1560 Rue Sherbrooke Est, Montréal, Québec H2L 4M1 (Canada)

    2016-05-15

    Purpose: An improvement in tissue assignment for low-dose rate brachytherapy (LDRB) patients using more accurate Monte Carlo (MC) dose calculation was accomplished with a metallic artifact reduction (MAR) method specific to dual-energy computed tomography (DECT). Methods: The proposed MAR algorithm followed a four-step procedure. The first step involved applying a weighted blend of both DECT scans (I {sub H/L}) to generate a new image (I {sub Mix}). This action minimized Hounsfield unit (HU) variations surrounding the brachytherapy seeds. In the second step, the mean HU of the prostate in I {sub Mix} was calculated and shifted toward the mean HU of the two original DECT images (I {sub H/L}). The third step involved smoothing the newly shifted I {sub Mix} and the two original I {sub H/L}, followed by a subtraction of both, generating an image that represented the metallic artifact (I {sub A,(H/L)}) of reduced noise levels. The final step consisted of subtracting the original I {sub H/L} from the newly generated I {sub A,(H/L)} and obtaining a final image corrected for metallic artifacts. Following the completion of the algorithm, a DECT stoichiometric method was used to extract the relative electronic density (ρ{sub e}) and effective atomic number (Z {sub eff}) at each voxel of the corrected scans. Tissue assignment could then be determined with these two newly acquired physical parameters. Each voxel was assigned the tissue bearing the closest resemblance in terms of ρ{sub e} and Z {sub eff}, comparing with values from the ICRU 42 database. A MC study was then performed to compare the dosimetric impacts of alternative MAR algorithms. Results: An improvement in tissue assignment was observed with the DECT MAR algorithm, compared to the single-energy computed tomography (SECT) approach. In a phantom study, tissue misassignment was found to reach 0.05% of voxels using the DECT approach, compared with 0.40% using the SECT method. Comparison of the DECT and SECT D

  10. Translational Bioinformatics for Diagnostic and Prognostic Prediction of Prostate Cancer in the Next-Generation Sequencing Era

    Directory of Open Access Journals (Sweden)

    Jiajia Chen

    2013-01-01

    Full Text Available The discovery of prostate cancer biomarkers has been boosted by the advent of next-generation sequencing (NGS technologies. Nevertheless, many challenges still exist in exploiting the flood of sequence data and translating them into routine diagnostics and prognosis of prostate cancer. Here we review the recent developments in prostate cancer biomarkers by high throughput sequencing technologies. We highlight some fundamental issues of translational bioinformatics and the potential use of cloud computing in NGS data processing for the improvement of prostate cancer treatment.

  11. Tissue viscoelasticity is related to tissue composition but may not fully predict the apparent-level viscoelasticity in human trabecular bone – An experimental and finite element study

    DEFF Research Database (Denmark)

    Ojanen, X.; Tanska, P.; Malo, M. K.H.

    2017-01-01

    Trabecular bone is viscoelastic under dynamic loading. However, it is unclear how tissue viscoelasticity controls viscoelasticity at the apparent-level. In this study, viscoelasticity of cylindrical human trabecular bone samples (n = 11, male, age 18–78 years) from 11 proximal femurs were charact......). These findings indicate that bone tissue viscoelasticity is affected by tissue composition but may not fully predict the macroscale viscoelasticity in human trabecular bone....

  12. Transrectal real-time tissue elastography targeted biopsy coupled with peak strain index improves the detection of clinically important prostate cancer.

    Science.gov (United States)

    Ma, Qi; Yang, Dong-Rong; Xue, Bo-Xin; Wang, Cheng; Chen, Han-Bin; Dong, Yun; Wang, Cai-Shan; Shan, Yu-Xi

    2017-07-01

    The focus of the present study was to evaluate transrectal real-time tissue elastography (RTE)-targeted two-core biopsy coupled with peak strain index for the detection of prostate cancer (PCa) and to compare this method with 10-core systematic biopsy. A total of 141 patients were enrolled for evaluation. The diagnostic value of peak strain index was assessed using a receiver operating characteristic curve. The cancer detection rates of the two approaches and corresponding positive cores and Gleason score were compared. The cancer detection rate per core in the RTE-targeted biopsy (44%) was higher compared with that in systematic biopsy (30%). The peak strain index value of PCa was higher compared with that of the benign lesion. PCa was detected with the highest sensitivity (87.5%) and specificity (85.5%) using the threshold value of a peak strain index of ≥5.97 with an area under the curve value of 0.95. When the Gleason score was ≥7, RTE-targeted biopsy coupled with peak strain index detected 95.6% of PCa cases, but 84.4% were detected using systematic biopsy. Peak strain index as a quantitative parameter may improve the differentiation of PCa from benign lesions in the prostate peripheral zone. Transrectal RTE-targeted biopsy coupled with peak strain index may enhance the detection of clinically significant PCa, particularly when combined with systematic biopsy.

  13. Incidence of late rectal bleeding in high-dose conformal radiotherapy of prostate cancer using equivalent uniform dose-based and dose-volume-based normal tissue complication probability models

    International Nuclear Information System (INIS)

    Soehn, Matthias; Yan Di; Liang Jian; Meldolesi, Elisa; Vargas, Carlos; Alber, Markus

    2007-01-01

    Purpose: Accurate modeling of rectal complications based on dose-volume histogram (DVH) data are necessary to allow safe dose escalation in radiotherapy of prostate cancer. We applied different equivalent uniform dose (EUD)-based and dose-volume-based normal tissue complication probability (NTCP) models to rectal wall DVHs and follow-up data for 319 prostate cancer patients to identify the dosimetric factors most predictive for Grade ≥ 2 rectal bleeding. Methods and Materials: Data for 319 patients treated at the William Beaumont Hospital with three-dimensional conformal radiotherapy (3D-CRT) under an adaptive radiotherapy protocol were used for this study. The following models were considered: (1) Lyman model and (2) logit-formula with DVH reduced to generalized EUD (3) serial reconstruction unit (RU) model (4) Poisson-EUD model, and (5) mean dose- and (6) cutoff dose-logistic regression model. The parameters and their confidence intervals were determined using maximum likelihood estimation. Results: Of the patients, 51 (16.0%) showed Grade 2 or higher bleeding. As assessed qualitatively and quantitatively, the Lyman- and Logit-EUD, serial RU, and Poisson-EUD model fitted the data very well. Rectal wall mean dose did not correlate to Grade 2 or higher bleeding. For the cutoff dose model, the volume receiving > 73.7 Gy showed most significant correlation to bleeding. However, this model fitted the data more poorly than the EUD-based models. Conclusions: Our study clearly confirms a volume effect for late rectal bleeding. This can be described very well by the EUD-like models, of which the serial RU- and Poisson-EUD model can describe the data with only two parameters. Dose-volume-based cutoff-dose models performed worse

  14. Antibody Responses to Prostate-Associated Antigens in Patients with Prostatitis and Prostate Cancer

    Science.gov (United States)

    Maricque, Brett B.; Eickhoff, Jens C.; McNeel, Douglas G.

    2010-01-01

    Background An important focus of tumor immunotherapy has been the identification of appropriate antigenic targets. Serum-based screening approaches have led to the discovery of hundreds of tumor-associated antigens recognized by IgG. Our efforts to identify immunologically recognized proteins in prostate cancer have yielded a multitude of antigens, however prioritizing these antigens as targets for evaluation in immunotherapies has been challenging. In this report, we set out to determine whether the evaluation of multiple antigenic targets would allow the identification of a subset of antigens that are common immunologic targets in patients with prostate cancer. Methods Using a phage immunoblot approach, we evaluated IgG responses in patients with prostate cancer (n=126), patients with chronic prostatitis (n=45), and men without prostate disease (n=53). Results We found that patients with prostate cancer or prostatitis have IgG specific for multiple common antigens. A subset of 23 proteins was identified to which IgG were detected in 38% of patients with prostate cancer and 33% patients with prostatitis versus 6% of controls (pprostate and prostate cancer, and suggest that IgG responses to a panel of commonly recognized prostate antigens could be potentially used in the identification of patients at risk for prostate cancer or as a tool to identify immune responses elicited to prostate tissue. PMID:20632317

  15. Deep learning for tissue microarray image-based outcome prediction in patients with colorectal cancer

    Science.gov (United States)

    Bychkov, Dmitrii; Turkki, Riku; Haglund, Caj; Linder, Nina; Lundin, Johan

    2016-03-01

    Recent advances in computer vision enable increasingly accurate automated pattern classification. In the current study we evaluate whether a convolutional neural network (CNN) can be trained to predict disease outcome in patients with colorectal cancer based on images of tumor tissue microarray samples. We compare the prognostic accuracy of CNN features extracted from the whole, unsegmented tissue microarray spot image, with that of CNN features extracted from the epithelial and non-epithelial compartments, respectively. The prognostic accuracy of visually assessed histologic grade is used as a reference. The image data set consists of digitized hematoxylin-eosin (H and E) stained tissue microarray samples obtained from 180 patients with colorectal cancer. The patient samples represent a variety of histological grades, have data available on a series of clinicopathological variables including long-term outcome and ground truth annotations performed by experts. The CNN features extracted from images of the epithelial tissue compartment significantly predicted outcome (hazard ratio (HR) 2.08; CI95% 1.04-4.16; area under the curve (AUC) 0.66) in a test set of 60 patients, as compared to the CNN features extracted from unsegmented images (HR 1.67; CI95% 0.84-3.31, AUC 0.57) and visually assessed histologic grade (HR 1.96; CI95% 0.99-3.88, AUC 0.61). As a conclusion, a deep-learning classifier can be trained to predict outcome of colorectal cancer based on images of H and E stained tissue microarray samples and the CNN features extracted from the epithelial compartment only resulted in a prognostic discrimination comparable to that of visually determined histologic grade.

  16. Unusual soft tissue uptake of F-18 sodium fluoride in three patients undergoing F-18 NaF PET/CT bone scans for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hawkins, Andrew S.; Howard, Brandon A. [Div. of Nuclear Medicine, Dept. of Radiology, Duke University Medical Center, Durham (United States)

    2017-09-15

    Three males aged 71 to 80 years with known stage IV metastatic prostate cancer underwent F-18 sodium fluoride (NaF) PET/CT to assess osseous metastatic disease burden and stability. In addition to F-18 NaF avid known osseous metastases, each patient also exhibited increased F-18 NaF activity in soft tissues. The first patient exhibited multiple F-18 NaF avid enlarged retroperitoneal and pelvic lymph nodes on consecutive PET/CT scans. The second patient demonstrated an F-18 NaF avid thyroid nodule on consecutive PET/CT scans. The third patient exhibited increased F-18 NaF activity in a hepatic metastasis.

  17. Apparent diffusion coefficient in the analysis of prostate cancer: determination of optimal b-value pair to differentiate normal from malignant tissue.

    Science.gov (United States)

    Adubeiro, Nuno; Nogueira, Maria Luísa; Nunes, Rita G; Ferreira, Hugo Alexandre; Ribeiro, Eduardo; La Fuente, José Maria Ferreira

    Determining optimal b-value pair for differentiation between normal and prostate cancer (PCa) tissues. Forty-three patients with diagnosis or PCa symptoms were included. Apparent diffusion coefficient (ADC) was estimated using minimum and maximum b-values of 0, 50, 100, 150, 200, 500s/mm2 and 500, 800, 1100, 1400, 1700 and 2000s/mm2, respectively. Diagnostic performances were evaluated when Area-under-the-curve (AUC)>95%. 15 of the 35 b-values pair surpassed this AUC threshold. The pair (50, 2000s/mm2) provided the highest AUC (96%) with ADC cutoff 0.89×10- 3 mm 2 /s, sensitivity 95.5%, specificity 93.2% and accuracy 94.4%. The best b-value pair was b=50, 2000s/mm2. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Phenotypic and genetic heterogeneity of tumor tissue and circulating tumor cells in patients with metastatic castrationresistant prostate cancer: a report from the PETRUS prospective study

    Science.gov (United States)

    Massard, Christophe; Oulhen, Marianne; Le Moulec, Sylvestre; Auger, Nathalie; Foulon, Stéphanie; Abou-Lovergne, Aurélie; Billiot, Fanny; Valent, Alexander; Marty, Virginie; Loriot, Yohann; Fizazi, Karim; Vielh, Philippe; Farace, Francoise

    2016-01-01

    Molecular characterization of cancer samples is hampered by tumor tissue availability in metastatic castration-resistant prostate cancer (mCRPC) patients. We reported the results of prospective PETRUS study of biomarker assessment in paired primary prostatic tumors, metastatic biopsies and circulating tumor cells (CTCs). Among 54 mCRPC patients enrolled, 38 (70%) had biopsies containing more than 50% tumour cells. 28 (52%) patients were analyzed for both tissue samples and CTCs. FISH for AR-amplification and TMPRSS2-ERG translocation were successful in 54% and 32% in metastatic biopsies and primary tumors, respectively. By comparing CellSearch and filtration (ISET)-enrichment combined to four color immunofluorescent staining, we showed that CellSearch and ISET isolated distinct subpopulations of CTCs: CTCs undergoing epithelial-to-mesenchymal transition, CTC clusters and large CTCs with cytomorphological characteristics but no detectable markers were isolated using ISET. Epithelial CTCs detected by the CellSearch were mostly lost during the ISET-filtration. AR-amplification was detected in CellSearch-captured CTCs, but not in ISET-enriched CTCs which harbor exclusively AR gain of copies. Eighty-eight percent concordance for ERG-rearrangement was observed between metastatic biopsies and CTCs even if additional ERG-alteration patterns were detected in ISET-enriched CTCs indicating a higher heterogeneity in CTCs. Molecular screening of metastatic biopsies is achievable in a multicenter context. Our data indicate that CTCs detected by the CellSearch and the ISET-filtration systems are not only phenotypically but also genetically different. Close attention must be paid to CTC characterization since neither approach tested here fully reflects the tremendous phenotypic and genetic heterogeneity present in CTCs from mCRPC patients. PMID:27391263

  19. Phenotypic and genetic heterogeneity of tumor tissue and circulating tumor cells in patients with metastatic castration-resistant prostate cancer: A report from the PETRUS prospective study.

    Science.gov (United States)

    Massard, Christophe; Oulhen, Marianne; Le Moulec, Sylvestre; Auger, Nathalie; Foulon, Stéphanie; Abou-Lovergne, Aurélie; Billiot, Fanny; Valent, Alexander; Marty, Virginie; Loriot, Yohann; Fizazi, Karim; Vielh, Philippe; Farace, Francoise

    2016-08-23

    Molecular characterization of cancer samples is hampered by tumor tissue availability in metastatic castration-resistant prostate cancer (mCRPC) patients. We reported the results of prospective PETRUS study of biomarker assessment in paired primary prostatic tumors, metastatic biopsies and circulating tumor cells (CTCs). Among 54 mCRPC patients enrolled, 38 (70%) had biopsies containing more than 50% tumour cells. 28 (52%) patients were analyzed for both tissue samples and CTCs. FISH for AR-amplification and TMPRSS2-ERG translocation were successful in 54% and 32% in metastatic biopsies and primary tumors, respectively. By comparing CellSearch and filtration (ISET)-enrichment combined to four color immunofluorescent staining, we showed that CellSearch and ISET isolated distinct subpopulations of CTCs: CTCs undergoing epithelial-to-mesenchymal transition, CTC clusters and large CTCs with cytomorphological characteristics but no detectable markers were isolated using ISET. Epithelial CTCs detected by the CellSearch were mostly lost during the ISET-filtration. AR-amplification was detected in CellSearch-captured CTCs, but not in ISET-enriched CTCs which harbor exclusively AR gain of copies. Eighty-eight percent concordance for ERG-rearrangement was observed between metastatic biopsies and CTCs even if additional ERG-alteration patterns were detected in ISET-enriched CTCs indicating a higher heterogeneity in CTCs.Molecular screening of metastatic biopsies is achievable in a multicenter context. Our data indicate that CTCs detected by the CellSearch and the ISET-filtration systems are not only phenotypically but also genetically different. Close attention must be paid to CTC characterization since neither approach tested here fully reflects the tremendous phenotypic and genetic heterogeneity present in CTCs from mCRPC patients.

  20. Comparison of Predictive Factors for Postoperative Incontinence of Holmium Laser Enucleation of the Prostate by the Surgeons' Experience During Learning Curve.

    Science.gov (United States)

    Shigemura, Katsumi; Tanaka, Kazushi; Yamamichi, Fukashi; Chiba, Koji; Fujisawa, Masato

    2016-03-01

    To detect predictive factors for postoperative incontinence following holmium laser enucleation of the prostate (HoLEP) according to surgeon experience (beginner or experienced) and preoperative clinical data. Of 224 patients, a total of 203 with available data on incontinence were investigated. The potential predictive factors for post-HoLEP incontinence included clinical factors, such as patient age, and preoperative urodynamic study results, including detrusor overactivity (DO). We also classified the surgeons performing the procedure according to their HoLEP experience: beginner (predictive factor at the super-short period (the next day of catheter removal: odds ratio [OR], 3.375; P=0.000). Additionally, patient age, surgeon mentorship (inverse correlation), and prostate volume were significant predictive factors at the 1-month interval after HoLEP (OR, 1.072; P=0.004; OR, 0.251; P=0.002; and OR, 1.008; P=0.049, respectively). With regards to surgeon experience, DO and preoperative International Prostate Symptom Score (inverse) at the super-short period, and patient age and mentorship (inverse correlation) at the 1-month interval after HoLEP (OR, 3.952; P=0.002; OR, 1.084; P=0.015; and OR,1.084; P=0.015; OR, 0.358; P=0.003, respectively) were significant predictive factors for beginners, and first desire to void (FDV) at 1 month after HoLEP (OR, 1.009; P=0.012) was a significant predictive factor for experienced surgeons in multivariate analysis. Preoperative DO, IPSS, patient age, and surgeon mentorship were significant predictive factors of postoperative patient incontinence for beginner surgeons, while FDV was a significant predictive factors for experienced surgeons. These findings should be taken into account by surgeons performing HoLEP to maximize the patient's quality of life with regards to urinary continence.

  1. Ability of preoperative 3.0-Tesla magnetic resonance imaging to predict the absence of side-specific extracapsular extension of prostate cancer.

    Science.gov (United States)

    Hara, Tomohiko; Nakanishi, Hiroyuki; Nakagawa, Tohru; Komiyama, Motokiyo; Kawahara, Takashi; Manabe, Tomoko; Miyake, Mototaka; Arai, Eri; Kanai, Yae; Fujimoto, Hiroyuki

    2013-10-01

    Recent studies have shown an improvement in prostate cancer diagnosis with the use of 3.0-Tesla magnetic resonance imaging. We retrospectively assessed the ability of this imaging technique to predict side-specific extracapsular extension of prostate cancer. From October 2007 to August 2011, prostatectomy was carried out in 396 patients after preoperative 3.0-Tesla magnetic resonance imaging. Among these, 132 (primary sample) and 134 patients (validation sample) underwent 12-core prostate biopsy at the National Cancer Center Hospital of Tokyo, Japan, and at other institutions, respectively. In the primary dataset, univariate and multivariate analyses were carried out to predict side-specific extracapsular extension using variables determined preoperatively, including 3.0-Tesla magnetic resonance imaging findings (T2-weighted and diffusion-weighted imaging). A prediction model was then constructed and applied to the validation study sample. Multivariate analysis identified four significant independent predictors (P Tesla diffusion-weighted magnetic resonance imaging findings, ≥2 positive biopsy cores on each side and a maximum percentage of positive cores ≥31% on each side. The negative predictive value was 93.9% in the combination model with these four predictors, meanwhile the positive predictive value was 33.8%. Good reproducibility of these four significant predictors and the combination model was observed in the validation study sample. The side-specific extracapsular extension prediction by the biopsy Gleason score and factors associated with tumor location, including a positive 3.0-Tesla diffusion-weighted magnetic resonance imaging finding, have a high negative predictive value, but a low positive predictive value. © 2013 The Japanese Urological Association.

  2. Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores

    DEFF Research Database (Denmark)

    Lecarpentier, Julie; Silvestri, Valentina; Kuchenbaecker, Karoline B.

    2017-01-01

    Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated-for the first time to our knowledge-associations of common genetic variants with breast and prostate cancer risks...

  3. Prognostic and predictive value of intact and cleaved forms of the urokinase plasminogen activator receptor in metastatic prostate cancer

    DEFF Research Database (Denmark)

    Almasi, Charlotte E; Brasso, Klaus; Iversen, Peter

    2011-01-01

    The purpose of this study was to investigate the prognostic value of different forms of the urokinase receptor, uPAR, in serum from prostate cancer (PC) patients.......The purpose of this study was to investigate the prognostic value of different forms of the urokinase receptor, uPAR, in serum from prostate cancer (PC) patients....

  4. Pre-therapeutic dosimetry of normal organs and tissues of {sup 177}Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kabasakal, Levent; AbuQbeitah, Mohammad; Ayguen, Aslan; Yeyin, Nami [Istanbul University, Department of Nuclear Medicine, Cerrahpasa Medical Faculty, Istanbul (Turkey); Ocak, Meltem [Istanbul University, Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul (Turkey); Demirci, Emre [Sisli Etfal Training and Research Hospital, Department of Nuclear Medicine, Istanbul (Turkey); Toklu, Turkay [Yeditepe University Medical Faculty, Department of Nuclear Medicine, Istanbul (Turkey)

    2015-12-15

    {sup 177}Lu-617-prostate-specific membrane antigen (PSMA) ligand seems to be a promising tracer for radionuclide therapy of progressive prostate cancer. However, there are no published data regarding the radiation dose given to the normal tissues. The aim of the present study was to estimate the pretreatment radiation doses in patients who will undergo radiometabolic therapy using a tracer amount of {sup 177}Lu-labeled PSMA ligand. The study included seven patients with progressive prostate cancer with a mean age of 63.9 ± 3.9 years. All patients had prior PSMA positron emission tomography (PET) imaging and had intense tracer uptake at the lesions. The injected {sup 177}Lu-PSMA-617 activity ranged from 185 to 210 MBq with a mean of 192.6 ± 11.0 MBq. To evaluate bone marrow absorbed dose 2-cc blood samples were withdrawn in short variable times (3, 15, 30, 60, and 180 min and 24, 48, and 120 h) after injection. Whole-body images were obtained at 4, 24, 48, and 120 h post-injection (p.i.). The geometric mean of anterior and posterior counts was determined through region of interest (ROI) analysis. Attenuation correction was applied using PSMA PET/CT images. The OLINDA/EXM dosimetry program was used for curve fitting, residence time calculation, and absorbed dose calculations. The calculated radiation-absorbed doses for each organ showed substantial variation. The highest radiation estimated doses were calculated for parotid glands and kidneys. Calculated radiation-absorbed doses per megabecquerel were 1.17 ± 0.31 mGy for parotid glands and 0.88 ± 0.40 mGy for kidneys. The radiation dose given to the bone marrow was significantly lower than those of kidney and parotid glands (p < 0.05). The calculated radiation dose to bone marrow was 0.03 ± 0.01 mGy/MBq. Our first results suggested that {sup 177}Lu-PSMA-617 therapy seems to be a safe method. The dose-limiting organ seems to be the parotid glands rather than kidneys and bone marrow. The lesion radiation doses are

  5. PHI and PCA3 improve the prognostic performance of PRIAS and Epstein criteria in predicting insignificant prostate cancer in men eligible for active surveillance.

    Science.gov (United States)

    Cantiello, Francesco; Russo, Giorgio Ivan; Cicione, Antonio; Ferro, Matteo; Cimino, Sebastiano; Favilla, Vincenzo; Perdonà, Sisto; De Cobelli, Ottavio; Magno, Carlo; Morgia, Giuseppe; Damiano, Rocco

    2016-04-01

    To assess the performance of prostate health index (PHI) and prostate cancer antigen 3 (PCA3) when added to the PRIAS or Epstein criteria in predicting the presence of pathologically insignificant prostate cancer (IPCa) in patients who underwent radical prostatectomy (RP) but eligible for active surveillance (AS). An observational retrospective study was performed in 188 PCa patients treated with laparoscopic or robot-assisted RP but eligible for AS according to Epstein or PRIAS criteria. Blood and urinary specimens were collected before initial prostate biopsy for PHI and PCA3 measurements. Multivariate logistic regression analyses and decision curve analysis were carried out to identify predictors of IPCa using the updated ERSPC definition. At the multivariate analyses, the inclusion of both PCA3 and PHI significantly increased the accuracy of the Epstein multivariate model in pred