Ten-core versus 16-core transrectal ultrasonography guided prostate biopsy for detection of prostatic carcinoma: a prospective comparative study in Indian population.

PubMed

Prakash, V Surya; Mohan, G Chandra; Krishnaiah, S Venkata; Vijaykumar, V; Babu, G Ramesh; Reddy, G Vijaya Bhaskar; Mahaboob, V S

2013-01-01

To compare the cancer detection rate in patients with raised serum prostate-specific antigen (PSA) or abnormal digital rectal examination (DRE) results between the 10-core and the 16-core biopsy techniques in an Indian population. Between November 2010 and November 2012, 95 men aged >50 years who presented to the Urology Department with lower urinary tract symptoms, elevated serum PSA, and/or abnormal DRE findings underwent transrectal ultrasonography (TRUS)-guided prostate biopsy. A total of 53 patients underwent 10-core biopsy and 42 patients underwent 16-core biopsy. Of the 53 men in the 10-core group, 8 had cancer, whereas in the 16-core biopsy group, 23 of 42 men had cancer. Detection of prostate cancer was significantly higher in patients who underwent 16-core biopsy than in those who underwent 10-core biopsy (P<0.001). Among the 95 men, 44 men had abnormal DRE findings (46.3%), of whom 23 showed cancer (52.27%). Of 51 men with normal DRE findings and elevated PSA, 8 men had malignancy with a cancer detection rate of 15.68%. Among 20 men with PSA between 4.1 and 10 ng/mL, 2 (10%) had cancer. In 31 men with PSA between 10.1 and 20 ng/mL, 3 cancers (9.67%) were detected, and in 44 men with PSA >20 ng/mL, 26 cancers were detected (59.09%). The cancer detection rate with 16-core TRUS-guided biopsy is significantly higher than that with 10-core biopsy (54.76% vs. 15.09%, P<0.001). In patients with both normal and abnormal DRE findings, 16-core biopsy has a better detection rate than the 10-core biopsy protocol. With increasing PSA, there is a high rate of detection of prostate cancer in both 10-core and 16-core biopsy patients.

Prostate: techniques, results, and potential applications of color Doppler US scanning.

PubMed

Rifkin, M D; Sudakoff, G S; Alexander, A A

1993-02-01

Color Doppler ultrasound (US) scanning and conventional endorectal gray-scale US of the prostate were performed in 619 patients. Pathologic correlation was available in all cases after US-guided transrectal biopsy. There were 132 cancers in 121 men, 13 foci of atypia in 10 men, 33 foci of inflammation in 31 men, and 469 benign lesions in 457 men. Two hundred seventy patients with abnormal areas of flow identified at color Doppler scanning also underwent spectral waveform analysis of the area of potential concern. No statistical difference in the mean resistive indexes was identified in any patient (P = .25; Scheffe F test, analysis of variance). All malignant lesions had abnormalities demonstrated at gray-scale US and/or focal or diffuse abnormal flow demonstrated at color Doppler scanning. Of the 132 cancers, 123 (93%) had corresponding gray-scale abnormalities and 114 (86%) demonstrated abnormal flow at color Doppler imaging. Nine of the 132 cancers (7%) had no obviously identifiable abnormality at gray-scale scanning but had distinctly abnormal flow at color Doppler scanning. Abnormal findings at color scanning without abnormal findings at gray-scale scanning occurred in eight of the 33 cases of inflammatory foci (24%) and in 24 of the 469 (5%) benign lesions.

The role of blood neutrophil count and the neutrophil-to-lymphocyte ratio as a predictive factor for prostate biopsy results.

PubMed

Kamali, Koosha; Ashrafi, Mojtaba; Shadpour, Pejman; Ameli, Mojtaba; Khayyamfar, Amirmahdi; Abolhasani, Maryam; Azizpoor, Amin

2018-04-01

It is apparent that prostate cancer has harmful effects on the erythrocytes, leucocytes, and platelets. In addition, it has been suggested that the toxic granules in neutrophils lead to inflammation in the cancerous tissues besides the activation of monocytes, so in this study we aimed to evaluate the blood neutrophil count besides the neutrophil-to-lymphocyte ratio as a predictive factor for prostate biopsy results and their relationship with prostate cancer grade in patients undergoing biopsy of the prostate. For all men with irritative lower urinary tract symptoms visiting Hasheminezhad Hospital from January to July 2015, in case of having a suspicious digital rectal examination or aged above 40 years, prostate-specific antigen was requested and in case of abnormal results, they underwent prostate biopsy. In order to examine the study hypothesis, the blood neutrophil count and the neutrophil-to-lymphocyte ratio were measured and compared with the abnormal prostate-specific antigen results and suspicious digital rectal examination. Among the 500 referred samples for biopsy, 352 (70.4%) had a negative biopsy result, while it was positive in the other 148 (29.6). The mean neutrophil count showed no statistical difference regarding the biopsy results (p = 0.381). When measuring the neutrophil-to-lymphocyte ratio again with biopsy results, no statistically significant difference was obtained based on the biopsy results (p = 0.112). Neutrophil count and neutrophil-to-lymphocyte ratio cannot be predictive factors for positive prostate cancer biopsy.

Characterization of Prostate-Specific Membrane Antigen (PSMA) for Use in Therapeutic and Diagnostic Strategies Against Prostate Cancer

DTIC Science & Technology

2001-07-01

Rogers, H. Ragde, G. M. Kenny, et al. 1999. Follow-up evaluation of a phase II prostate cancer vaccine trial. Prostate 40: 125-129. 69. Troyer, J. K., M...Slusher, D. Price, and J. T. Coyle. 1993. Abnormal acidic amino acids and N-acetylaspartylglutamate in hereditary canine motoneuron disease. Brain Res...levels were at least 10-fold higher, re- promoter, that of the herpesvirus thymidine kinase flecting the greater basal activity of these promoters in gene

Plasma genetic and genomic abnormalities predict treatment response and clinical outcome in advanced prostate cancer.

PubMed

Xia, Shu; Kohli, Manish; Du, Meijun; Dittmar, Rachel L; Lee, Adam; Nandy, Debashis; Yuan, Tiezheng; Guo, Yongchen; Wang, Yuan; Tschannen, Michael R; Worthey, Elizabeth; Jacob, Howard; See, William; Kilari, Deepak; Wang, Xuexia; Hovey, Raymond L; Huang, Chiang-Ching; Wang, Liang

2015-06-30

Liquid biopsies, examinations of tumor components in body fluids, have shown promise for predicting clinical outcomes. To evaluate tumor-associated genomic and genetic variations in plasma cell-free DNA (cfDNA) and their associations with treatment response and overall survival, we applied whole genome and targeted sequencing to examine the plasma cfDNAs derived from 20 patients with advanced prostate cancer. Sequencing-based genomic abnormality analysis revealed locus-specific gains or losses that were common in prostate cancer, such as 8q gains, AR amplifications, PTEN losses and TMPRSS2-ERG fusions. To estimate tumor burden in cfDNA, we developed a Plasma Genomic Abnormality (PGA) score by summing the most significant copy number variations. Cox regression analysis showed that PGA scores were significantly associated with overall survival (p < 0.04). After androgen deprivation therapy or chemotherapy, targeted sequencing showed significant mutational profile changes in genes involved in androgen biosynthesis, AR activation, DNA repair, and chemotherapy resistance. These changes may reflect the dynamic evolution of heterozygous tumor populations in response to these treatments. These results strongly support the feasibility of using non-invasive liquid biopsies as potential tools to study biological mechanisms underlying therapy-specific resistance and to predict disease progression in advanced prostate cancer.

Androgen receptor and immune inflammation in benign prostatic hyperplasia and prostate cancer

PubMed Central

Izumi, Kouji; Li, Lei; Chang, Chawnshang

2014-01-01

Both benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are frequent diseases in middle-aged to elderly men worldwide. While both diseases are linked to abnormal growth of the prostate, the epidemiological and pathological features of these two prostate diseases are different. BPH nodules typically arise from the transitional zone, and, in contrast, PCa arises from the peripheral zone. Androgen deprivation therapy alone may not be sufficient to cure these two prostatic diseases due to its undesirable side effects. The alteration of androgen receptor-mediated inflammatory signals from infiltrating immune cells and prostate stromal/epithelial cells may play key roles in those unwanted events. Herein, this review will focus on the roles of androgen/androgen receptor signals in the inflammation-induced progression of BPH and PCa. PMID:26594314

[The value of PHI/PCA3 in the early diagnosis of prostate cancer].

PubMed

Tan, S J; Xu, L W; Xu, Z; Wu, J P; Liang, K; Jia, R P

2016-01-12

To investigate the value of prostate health index (PHI) and prostate cancer gene 3 (PCA3) in the early diagnosis of prostate cancer (PCa). A total of 190 patients with abnormal serum prostate specific antigen (PSA) or abnormal digital rectal examination were enrolled. They were all underwent initial biopsy and 11 of them were also underwent repeated biopsy. In addition, 25 healthy cases (with normal digital rectal examination and PSA<4 ng/ml) were the control group.The PHI and PCA3 were detected by using immunofluorescence and Loop-Mediated Isothermal Amplification (LAMP). The sensitivity and specificity of diagnosis were determined by ROC curve.In addition, the relationship between PHI/PSA and the Gleason score and clinical stage were analyzed. A total of 89 patients were confirmed PCa by Pathological diagnosis. The other 101 patients were diagnosed as benign prostatic hyperplasia (BPH). The sensitivity and specificity of PCA3 test were 85.4% was 92.1%. Area under curve (AUC) of PHI is higher than AUC of PSA (0.727>0.699). The PHI in peripheral blood was positively correlated with Gleason score and clinical stage. The detection of PCA3 and PHI shows excellent detecting effectiveness. Compared with single PSA, the combined detection of PHI and PCA3 improved the diagnostic specificity. It can provide a new method for the early diagnosis in prostate cancer and avoid unnecessary biopsies.

Reduced plasma levels of coagulation factors in relation to prostate cancer.

PubMed

Beecken, Wolf-Dietrich; Bentas, Wassilios; Engels, Knut; Glienke, Wolfgang; Urbschat, Anja; Jonas, Dietger; Binder, Jochen; Scharrer, Inge

2002-10-01

Prostate cancer has historically been associated with coagulation abnormalities. This study was undertaken to investigate the prevalence of abnormalities of coagulation factors in patients with prostate cancer before and after radical prostatectomy (RP). Because coagulation factors have been shown to be involved in tumor angiogenesis, the vascular density of the prostate tumors was assessed. Plasma of 40 consecutive patients with histologically proven prostate cancer was investigated pre-RP and post-RP. The antigen level for antithrombin, plasminogen activator inhibitor-1, and heparin cofactor-II, and the plasma activity of antithrombin and plasminogen were determined by using immunologic and chromogenic assays. The values of these assays were compared with a group of 28 male, age-matched patients without any evidence of cancer and 18 patients with orthopedic interventions preoperatively and postoperatively. The vascular density of the prostate tumors was assessed by staining paraffin sections with an antibody to CD34. The median plasma antigen levels and/or activities of the investigated factors were below normal in the prostate cancer patients before RP. Furthermore, coagulation factors were significantly lower than in the age-matched control group and patients before and after orthopedic surgery. In prostate cancer patients, the median values of all investigated factors went up to normal levels within 2 weeks after RP, whereas postsurgical levels in orthopedic patients remained stable. No correlations to tumor parameters have been observed. We assume that the reduction of these coagulation factors is a principle concept in prostate cancer that needs further investigation. Copyright 2002 Wiley-Liss, Inc.

Finding a Cure: HBCU Students, Researchers on Front Lines of Fight against Prostate Cancer

ERIC Educational Resources Information Center

Hayes, Dianne

2012-01-01

Prostate cancer is a disease in which abnormal cells in the body grow out of control in the walnut-sized prostate gland. According to the Centers for Disease Control and Prevention, African-American men have a higher rate of getting the disease and dying from it than any other racial or ethnic group. One in five African-American men has a chance…

Diagnosis and follow-up of chronic bacterial prostatitis with recurrent urinary tract infection detected by 67Ga scintigraphy and SPECT/CT.

PubMed

Kim, Jun Ho; Baek, Ji-Hyeon; Lee, Jin Soo; Hyun, In Young

2013-11-01

Half of male populations will have symptoms and signs of prostatitis in their lifetime. There is controversy concerning diagnosis of prostatitis with (67)Ga scintigraphy because the focal midline pelvic uptake is usually considered to be physiologic uptake in colon. The authors describe (67)Ga scintigraphy and SPECT/CT findings of a 58-year-old man with right flank pain and fever. The examination demonstrated abnormal uptake of Ga within the prostate and right kidney upper pole, suggesting prostatitis and acute pyelonephritis (APN) contemporary. After completion of antibiotic treatment, follow-up scintigraphy and SPECT/CT showed complete resolution of APN, but uptake remained within the prostate.

Detection rate of prostate cancer following biopsy among the northern Han Chinese population: a single-center retrospective study of 1022 cases.

PubMed

Jia, Yong; Zhu, Lei-Yi; Xian, Yu-Xin; Sun, Xiao-Qing; Gao, Jian-Gang; Zhang, Xin-Hong; Hou, Si-Chuan; Zhang, Chang-Cun; Liu, Zhao-Xu

2017-08-29

Prostate cancer is known to have ethnic and regional differences. The study aimed to clinically evaluate the detection rate of prostate cancer on transrectal ultrasonography (TRUS)-guided prostate biopsy and analyze its characteristics among the northern Han Chinese population at a single center. Between October 2009 and September 2016, a total of 1027 Chinese men, who had undergone TRUS-guided prostate biopsy at Qingdao Municipal Hospital, were retrospectively analyzed. Prostate biopsies were performed in the case of an abnormally elevated serum PSA level, and/or abnormal digital rectal examination (DRE) findings, and/or suspicious prostatic imaging findings. Of the 1022 men enrolled in the analysis, 438 patients (42.8%) were diagnosed with prostate adenocarcinoma histologically. When serum PSA levels were divided into five subgroups (less than 4.0, 4.0 to 10.0, 10.0 to 20.0, 20.0 to 100.0, and ≥ 100.0 ng/ml), the detection rates of prostate cancer were 12.4, 15.9, 34.1, 66.2, and 93.8%, respectively. With serum PSA levels of 4.0 to 10.0 ng/ml, the cancer detection rates for a normal DRE and a suspect DRE finding were 13.5 and 58.2%, respectively. Accordingly, the cancer detection rates for a normal imaging and a suspect imaging finding were 13.5 and 58.2%, respectively. Besides, a large proportion of the patients were in the clinically advanced stage. The present study data reported a relatively higher prostate cancer detection rate of 42.8% and that the majority of the patients presented with clinically advanced prostate cancers within a local clinical urologic practice. An early detection and screening program for prostate cancer is of great need to reduce the burden from this disease among the northern Han Chinese population.

A microdissection approach to detect molecular markers during progression of prostate cancer.

PubMed Central

Berthon, P.; Dimitrov, T.; Stower, M.; Cussenot, O.; Maitland, N. J.

1995-01-01

To investigate the underlying mechanisms of carcinogenesis, we have developed a technique to determine the frequency of genetic changes in prostatic carcinoma tissue. We have demonstrated that at a ratio of between 1:4 and 1:9 mutant-normal alleles, the signal from a mutant TP53 allele is not apparent after polymerase chain reaction (PCR) amplification and further direct sequencing or single-strand conformation polymorphism (SSCP) analysis. To bypass this problem, which is inherent in the heterogeneity of the prostate tissue and of the tumour, we selected areas of graded prostate tumours (Gleason score) from cryosectioned preparations and microdissected these cells (20-100 cells). After anionic resin removal of proteins, PCR amplification of TP53 gene exons 5/6 and SSCP analysis, an abnormal SSCP band shift was observed in suspected tumour cells, compared with microdissected stromal cells used as an internal control, while (1) a crude preparation of tissue DNA carrying the tumour did not show any abnormality and (2) immunostaining by a set of monoclonal antibodies against TP53 protein remained negative. Nucleotide sequence analysis of the different bands confirmed the presence of a mutation in the TP53 gene exon 6 position 13,336 in an abnormal band for one specimen, while no mutation was detected in the normal SSCP band. By targeting recognised tumour cells we can find DNA mutations which are undetectable using the standard technique of whole-tissue DNA extraction, particularly in a heterogeneous tumour such as carcinoma of the prostate. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7547246

Health perceptions in patients who undergo screening and workup for prostate cancer.

PubMed

Katz, David A; Jarrard, David F; McHorney, Colleen A; Hillis, Stephen L; Wiebe, Donald A; Fryback, Dennis G

2007-02-01

False-positive screening tests may induce persistent psychological distress. This study was designed to determine whether a positive screening test with negative biopsy findings for prostate cancer is associated with worsened mental health during short-term follow-up. We conducted a cross-sectional telephone survey of two groups of men approximately 2 months after testing: group 1, 109 men with an abnormal prostate-specific antigen level or digital rectal examination findings but with negative biopsy findings for prostate cancer; and group 2, 101 age-matched primary care patients with PSA screening levels in the reference range (less than 4 ng/mL). Primary outcomes included state anxiety and prostate cancer-related worry. Secondary outcomes included Medical Outcomes Study Short Form 36-item Health Survey subscales and sexual function items. Multivariate regression techniques were used to adjust for differences in baseline covariates. Group 1 patients were more worried than group 2 patients about getting prostate cancer (mean worry 3.9 versus 4.5, P = 0.0001, using a 5-point scale, with 1 indicating extreme worry and 5 no worry). Group 1 patients also perceived their risk of prostate cancer to be significantly greater than that of controls (P = 0.001). No significant differences were found across state anxiety or Medical Outcomes Study Short Form 36-item Health Survey subscales. Sexual bother was greater for group 1 patients, with 19% reporting that sexual function was a moderate to big problem compared with 10% of group 2 patients (P = 0.0001). Men with abnormal prostate cancer screening tests report increased cancer-related worry and more problems with sexual function, despite having a negative biopsy result. Effective counseling interventions are needed before prostate cancer screening and during follow-up.

The Diagnostic Performance of Multiparametric Magnetic Resonance Imaging to Detect Significant Prostate Cancer.

PubMed

Thompson, J E; van Leeuwen, P J; Moses, D; Shnier, R; Brenner, P; Delprado, W; Pulbrook, M; Böhm, M; Haynes, A M; Hayen, A; Stricker, P D

2016-05-01

We assess the accuracy of multiparametric magnetic resonance imaging for significant prostate cancer detection before diagnostic biopsy in men with an abnormal prostate specific antigen/digital rectal examination. A total of 388 men underwent multiparametric magnetic resonance imaging, including T2-weighted, diffusion weighted and dynamic contrast enhanced imaging before biopsy. Two radiologists used PI-RADS to allocate a score of 1 to 5 for suspicion of significant prostate cancer (Gleason 7 with more than 5% grade 4). PI-RADS 3 to 5 was considered positive. Transperineal template guided mapping biopsy of 18 regions (median 30 cores) was performed with additional manually directed cores from magnetic resonance imaging positive regions. The anatomical location, size and grade of individual cancer areas in the biopsy regions (18) as the primary outcome and in prostatectomy specimens (117) as the secondary outcome were correlated to the magnetic resonance imaging positive regions. Of the 388 men who were enrolled in the study 344 were analyzed. Multiparametric magnetic resonance imaging was positive in 77.0% of patients, 62.5% had prostate cancer and 41.6% had significant prostate cancer. The detection of significant prostate cancer by multiparametric magnetic resonance imaging had a sensitivity of 96%, specificity of 36%, negative predictive value of 92% and positive predictive value of 52%. Adding PI-RADS to the multivariate model, including prostate specific antigen, digital rectal examination, prostate volume and age, improved the AUC from 0.776 to 0.879 (p <0.001). Anatomical concordance analysis showed a low mismatch between the magnetic resonance imaging positive regions and biopsy positive regions (4 [2.9%]), and the significant prostate cancer area in the radical prostatectomy specimen (3 [3.3%]). In men with an abnormal prostate specific antigen/digital rectal examination, multiparametric magnetic resonance imaging detected significant prostate cancer with an excellent negative predictive value and moderate positive predictive value. The use of multiparametric magnetic resonance imaging to diagnose significant prostate cancer may result in a substantial number of unnecessary biopsies while missing a minimum of significant prostate cancers. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Left lobe of the prostate during clinical prostate cancer screening: the dark side of the gland for right-handed examiners.

PubMed

Ploussard, G; Nicolaiew, N; Mongiat-Artus, P; Terry, S; Allory, Y; Vacherot, F; Abbou, C-C; Desgrandchamps, F; Salomon, L; de la Taille, A

2014-06-01

The predictive value of the abnormality side during digital rectal examination (DRE) has never been studied, suggesting that physicians examined the left lobe of the gland as well as the right lobe. We aimed to assess the predictive value of the side of DRE abnormality for prostate cancer (PCa) detection and aggressiveness in right-handed urologists. An analysis of a prospective database was carried out that included all consecutive men undergoing prostate biopsies between 2001 and 2012. The main end point was the predictive value of the abnormality side during DRE for cancer detection in clinically suspicious unilateral T2 disease. The diagnostic performance of left- versus right-sided abnormality was also assessed in terms of sensitivity, specificity and negative/positive predictive values. Overall, 308 patients had a suspicious unilateral clinical disease (detection rate 57.5%). The cancer detection rate was significantly higher in case of left-sided compared with right-sided clinical T2 stage (odds ratio 2.1). In case of left-sided disease, the number of positive cores, the rate of perineural invasion, the rate of primary grade 4 pattern and the percentage of cancer involvement per core were significantly higher compared with those reported for right-sided disease. The predictive value of abnormality laterality for cancer detection and aggressiveness remained statistically independent in multivariate models. The positive predictive value for cancer detection was 64.6 in case of suspicious left-sided disease versus 46.9 in case of right-sided disease. The risks of detecting PCa and aggressive disease on biopsy are significantly higher when DRE reveals a suspicious left-sided clinical disease as compared with right-sided disease. Right-handed physicians should be aware of this variance in diagnostic performance and potential underdetection of left-sided clinical disease, and should improve their examination of the left lobe of the gland by conducting longer exams or changing the patient's position.

Vertebral Hemangioma Mimicking Bone Metastasis in 68Ga-PSMA Ligand PET/CT.

PubMed

Artigas, Carlos; Otte, François-Xavier; Lemort, Marc; van Velthoven, Roland; Flamen, Patrick

2017-05-01

Ga-PSMA PET/CT was performed in a 68-year-old man to evaluate recurrent prostate cancer due to elevated serum prostate-specific antigen level. Images showed a focal uptake in the prostatic gland, suggesting local relapse, and an intense uptake in the 12th thoracic vertebra, with no morphological abnormalities in CT slices. In order to confirm extraprostatic disease and before radiotherapy planning, a full-spine MRI was performed, resulting with the morphological pattern of a vertebral hemangioma. Hystological analysis confirmed the local relapse in the prostate. No radiotherapy treatment was given to the vertebra, and after 1 year of follow-up without systemic treatment, prostate-specific antigen is still undetectable.

False Positive Uptake in Bilateral Gynecomastia on 68Ga-PSMA PET/CT Scan.

PubMed

Sasikumar, Arun; Joy, Ajith; Nair, Bindu P; Pillai, M R A; Madhavan, Jayaprakash

2017-09-01

A 66-year-old man on hormonal therapy with prostate cancer was referred for Ga-PSMA PET/CT scan for biochemical recurrence. Ga-PSMA PET/CT scan detected moderate heterogeneous tracer concentration in bilateral breast parenchyma, in addition to the abnormal tracer concentration in enlarged prostate gland, right external iliac lymph node, and sclerotic lesion in L4 vertebra. On clinical examination, he was found to have bilateral gynecomastia. Abnormal concentration of Ga-PSMA in breast cancer is now well known, and in this context, it is important to know that tracer localization can occur in gynecomastia as well, as evidenced in this case.

Screening prostate cancer using a portable near infrared scanning imaging unit with an optical fiber-based rectal probe

NASA Astrophysics Data System (ADS)

Pu, Yang; Wang, Wubao; Tang, Guichen; Budansky, Yury; Sharonov, Mikhail; Xu, Min; Achilefu, Samuel; Eastham, James A.; Alfano, Robert R.

2012-01-01

A portable near infrared scanning polarization imaging unit with an optical fiber-based rectal probe, namely Photonic Finger, was designed and developed o locate the 3D position of abnormal prostate site inside normal prostate tissue. An inverse algorithm, Optical Tomography using Independent Component Analysis (OPTICA) was improved particularly to unmix the signal from targets (cancerous tissue) embedded in a turbid medium (normal tissue) in the backscattering imaging geometry. Photonic Finger combined with OPTICA was tested to characterize different target(s) inside different tissue medium, including cancerous prostate tissue embedded by large piece of normal tissue.

Investigation of factors affecting hypothermic pelvic tissue cooling using bio-heat simulation based on MRI-segmented anatomic models.

PubMed

Lin, Yuting; Lin, Wei-Ching; Fwu, Peter T; Shih, Tzu-Ching; Yeh, Lee-Ren; Su, Min-Ying; Chen, Jeon-Hor

2015-10-01

This study applied a simulation method to map the temperature distribution based on magnetic resonance imaging (MRI) of individual patients, and investigated the influence of different pelvic tissue types as well as the choice of thermal property parameters on the efficiency of endorectal cooling balloon (ECB). MR images of four subjects with different prostate sizes and pelvic tissue compositions, including fatty tissue and venous plexus, were analyzed. The MR images acquired using endorectal coil provided a realistic geometry of deformed prostate that resembled the anatomy in the presence of ECB. A single slice with the largest two-dimensional (2D) cross-sectional area of the prostate gland was selected for analysis. The rectal wall, prostate gland, peri-rectal fatty tissue, peri-prostatic fatty tissue, peri-prostatic venous plexus, and urinary bladder were manually segmented. Pennes' bioheat thermal model was used to simulate the temperature distribution dynamics, by using an in-house finite element mesh based solver written in MATLAB. The results showed that prostate size and periprostatic venous plexus were two major factors affecting ECB cooling efficiency. For cases with negligible amount of venous plexus and small prostate, the average temperature in the prostate and neurovascular bundles could be cooled down to 25 °C within 30 min. For cases with abundant venous plexus and large prostate, the temperature could not reach 25 °C at the end of 3 h cooling. Large prostate made the cooling difficult to propagate through. The impact of fatty tissue on cooling effect was small. The filling of bladder with warm urine during the ECB cooling procedure did not affect the temperature in the prostate or NVB. In addition to the 2D simulation, in one case a 3D pelvic model was constructed for volumetric simulation. It was found that the 2D slice with the largest cross-sectional area of prostate had the most abundant venous plexus, and was the most difficult slice to cool, thus it may provide a conservative prediction of the cooling effect. This feasibility study demonstrated that the simulation tool could potentially be used for adjusting the setting of ECB for individual patients during hypothermic radical prostatectomy. Further studies using MR thermometry are required to validate the in silico results obtained using simulation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Investigation of factors affecting hypothermic pelvic tissue cooling using bio-heat simulation based on MRI-segmented anatomic models

PubMed Central

Lin, Yuting; Lin, Wei-Ching; Fwu, Peter T.; Shih, Tzu-Ching; Yeh, Lee-Ren; Su, Min-Ying; Chen, Jeon-Hor

2015-01-01

This study applied a simulation method to map the temperature distribution based on magnetic resonance imaging (MRI) of individual patients, and investigated the influence of different pelvic tissue types as well as the choice of thermal property parameters on the efficiency of endorectal cooling balloon (ECB). MR images of four subjects with different prostate sizes and pelvic tissue compositions, including fatty tissue and venous plexus, were analyzed. The MR images acquired using endorectal coil provided a realistic geometry of deformed prostate that resembled the anatomy in the presence of ECB. A single slice with the largest two-dimensional (2D) cross-sectional area of the prostate gland was selected for analysis. The rectal wall, prostate gland, peri-rectal fatty tissue, peri-prostatic fatty tissue, peri-prostatic venous plexus, and urinary bladder were manually segmented. Pennes’ bioheat thermal model was used to simulate the temperature distribution dynamics, by using an in-house finite element mesh based solver written in Matlab. The results showed that prostate size and periprostatic venous plexus were two major factors affecting ECB cooling efficiency. For cases with negligible amount of venous plexus and small prostate, the averaged temperature in the prostate and neurovascular bundles could be cooled down to 25°C within 30 minutes. For cases with abundant venous plexus and large prostate, the temperature could not reach 25°C at the end of 3 hours cooling. Large prostate made the cooling difficult to propagate through. The impact of fatty tissue on cooling effect was small. The filling of bladder with warm urine during the ECB cooling procedure did not affect the temperature in the prostate or NVB. In addition to the 2D simulation, in one case a 3D pelvic model was constructed for volumetric simulation. It was found that the 2D slice with the largest cross-sectional area of prostate had the most abundant venous plexus, and was the most difficult slice to cool, thus it may provide a conservative prediction of the cooling effect. This feasibility study demonstrated that the simulation tool could potentially be used for adjusting the setting of ECB for individual patients during hypothermic radical prostatectomy. Further studies using MR thermometry are required to validate the in silico results obtained using simulation. PMID:26198131

Simulation-based training for prostate surgery.

PubMed

Khan, Raheej; Aydin, Abdullatif; Khan, Muhammad Shamim; Dasgupta, Prokar; Ahmed, Kamran

2015-10-01

To identify and review the currently available simulators for prostate surgery and to explore the evidence supporting their validity for training purposes. A review of the literature between 1999 and 2014 was performed. The search terms included a combination of urology, prostate surgery, robotic prostatectomy, laparoscopic prostatectomy, transurethral resection of the prostate (TURP), simulation, virtual reality, animal model, human cadavers, training, assessment, technical skills, validation and learning curves. Furthermore, relevant abstracts from the American Urological Association, European Association of Urology, British Association of Urological Surgeons and World Congress of Endourology meetings, between 1999 and 2013, were included. Only studies related to prostate surgery simulators were included; studies regarding other urological simulators were excluded. A total of 22 studies that carried out a validation study were identified. Five validated models and/or simulators were identified for TURP, one for photoselective vaporisation of the prostate, two for holmium enucleation of the prostate, three for laparoscopic radical prostatectomy (LRP) and four for robot-assisted surgery. Of the TURP simulators, all five have demonstrated content validity, three face validity and four construct validity. The GreenLight laser simulator has demonstrated face, content and construct validities. The Kansai HoLEP Simulator has demonstrated face and content validity whilst the UroSim HoLEP Simulator has demonstrated face, content and construct validity. All three animal models for LRP have been shown to have construct validity whilst the chicken skin model was also content valid. Only two robotic simulators were identified with relevance to robot-assisted laparoscopic prostatectomy, both of which demonstrated construct validity. A wide range of different simulators are available for prostate surgery, including synthetic bench models, virtual-reality platforms, animal models, human cadavers, distributed simulation and advanced training programmes and modules. The currently validated simulators can be used by healthcare organisations to provide supplementary training sessions for trainee surgeons. Further research should be conducted to validate simulated environments, to determine which simulators have greater efficacy than others and to assess the cost-effectiveness of the simulators and the transferability of skills learnt. With surgeons investigating new possibilities for easily reproducible and valid methods of training, simulation offers great scope for implementation alongside traditional methods of training. © 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.

Vinclozolin Exposure in Utero Induces Postpubertal Prostatitis and Reduces Sperm Production via a Reversible Hormone-Regulated Mechanism

PubMed Central

Cowin, Prue A.; Gold, Elspeth; Aleksova, Jasna; O'Bryan, Moira K.; Foster, Paul M. D.; Scott, Hamish S.; Risbridger, Gail P.

2010-01-01

Vinclozolin is an endocrine-disrupting chemical (EDC) that binds with high affinity to the androgen receptor (AR) and blocks the action of gonadal hormones on male reproductive organs. An alternative mechanism of action of Vinclozolin involves transgenerational effects on the male reproductive tract. We previously reported in utero Vinclozolin exposure-induced prostatitis (prostate inflammation) in postpubertal rats concurrent with down-regulation of AR and increased nuclear factor-κB activation. We postulated the male reproductive abnormalities induced by in utero Vinclozolin exposure could be reversed by testosterone supplementation, in contrast to the permanent modifications involving DNA methyltransferases (Dnmts) described by others. To test this hypothesis, we administered high-dose testosterone at puberty to Vinclozolin-treated rats and determined the effect on anogenital distance (AGD); testicular germ cell apoptosis, concentration of elongated spermatids, and the onset of prostatitis. Concurrently we examined Dnmt1, −3A, −3B, and −3L mRNA expression. Consistent with previous reports, in utero exposure to Vinclozolin significantly reduced AGD, increased testicular germ cell apoptosis 3-fold, reduced elongated spermatid number by 40%, and induced postpubertal prostatitis in 100% of exposed males. Administration of high-dose testosterone (25 mg/kg) at puberty normalized AGD, reduced germ cell apoptosis, and restored elongated spermatid number. Testosterone restored AR and nuclear factor-κB expression in the prostate and abolished Vinclozolin-induced prostatitis. Altered Dnmt expression was evident with in utero Vinclozolin exposure and was not normalized after testosterone treatment. These data demonstrate in utero Vinclozolin-induced male reproductive tract abnormalities are AR mediated and reversible and involve a mechanism independent of Dnmt expression. PMID:20056826

Vinclozolin exposure in utero induces postpubertal prostatitis and reduces sperm production via a reversible hormone-regulated mechanism.

PubMed

Cowin, Prue A; Gold, Elspeth; Aleksova, Jasna; O'Bryan, Moira K; Foster, Paul M D; Scott, Hamish S; Risbridger, Gail P

2010-02-01

Vinclozolin is an endocrine-disrupting chemical (EDC) that binds with high affinity to the androgen receptor (AR) and blocks the action of gonadal hormones on male reproductive organs. An alternative mechanism of action of Vinclozolin involves transgenerational effects on the male reproductive tract. We previously reported in utero Vinclozolin exposure-induced prostatitis (prostate inflammation) in postpubertal rats concurrent with down-regulation of AR and increased nuclear factor-kappaB activation. We postulated the male reproductive abnormalities induced by in utero Vinclozolin exposure could be reversed by testosterone supplementation, in contrast to the permanent modifications involving DNA methyltransferases (Dnmts) described by others. To test this hypothesis, we administered high-dose testosterone at puberty to Vinclozolin-treated rats and determined the effect on anogenital distance (AGD); testicular germ cell apoptosis, concentration of elongated spermatids, and the onset of prostatitis. Concurrently we examined Dnmt1, -3A, -3B, and -3L mRNA expression. Consistent with previous reports, in utero exposure to Vinclozolin significantly reduced AGD, increased testicular germ cell apoptosis 3-fold, reduced elongated spermatid number by 40%, and induced postpubertal prostatitis in 100% of exposed males. Administration of high-dose testosterone (25 mg/kg) at puberty normalized AGD, reduced germ cell apoptosis, and restored elongated spermatid number. Testosterone restored AR and nuclear factor-kappaB expression in the prostate and abolished Vinclozolin-induced prostatitis. Altered Dnmt expression was evident with in utero Vinclozolin exposure and was not normalized after testosterone treatment. These data demonstrate in utero Vinclozolin-induced male reproductive tract abnormalities are AR mediated and reversible and involve a mechanism independent of Dnmt expression.

A 'One Stop' Prostate Clinic for rural and remote men: a report on the first 200 patients.

PubMed

McCombie, Steve P; Hawks, Cynthia; Emery, Jon D; Hayne, Dickon

2015-10-01

To report on the structure and outcomes of a new 'One Stop' Prostate Clinic (OSPC) designed specifically for rural and remote men. Prospective cohort study of the first 200 rural or remote men to access a new OSPC at a public tertiary-level hospital in Western Australia between August 2011 and August 2014. Men attended for urological assessment, and proceeded to same-day transrectal ultrasonography-guided prostate biopsies, if appropriate. Referral criteria were either two abnormal age-related prostate-specific antigen (PSA) levels in the absence of urinary tract infection (UTI), or an abnormal digital rectal examination (DRE) regardless of PSA level. The median (range) distance travelled was 1545 (56-3229) km and median (range) time from referral to assessment was 33 (2-165) days. The median (range) age was 62 (38-85) years, PSA level was 6.7 (0.5-360) ng/mL and 39% (78/200) had a suspicious DRE. In all, 92% (184/200) of men proceeded to prostate biopsies, and 60% (111/184) of these men were diagnosed with prostate cancer. Our complication rate was 3.5% (6/172). Radical prostatectomy (46/111), active surveillance (28/111) and external beam radiation therapy (26/111) were the commonest subsequent treatment methods. A $1045 (Australian dollars) cost-saving per person was estimated based on the reduced need for travel with the OSPC model. The OSPC is an effective and efficient model for assessing men suspected of having prostate cancer living in rural and remote areas of Western Australia, and this model may be applicable to other areas. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

Expression of LIM kinase 1 is associated with reversible G1/S phase arrest, chromosomal instability and prostate cancer.

PubMed

Davila, Monica; Jhala, Darshana; Ghosh, Debashis; Grizzle, William E; Chakrabarti, Ratna

2007-06-08

LIM kinase 1 (LIMK1), a LIM domain containing serine/threonine kinase, modulates actin dynamics through inactivation of the actin depolymerizing protein cofilin. Recent studies have indicated an important role of LIMK1 in growth and invasion of prostate and breast cancer cells; however, the molecular mechanism whereby LIMK1 induces tumor progression is unknown. In this study, we investigated the effects of ectopic expression of LIMK1 on cellular morphology, cell cycle progression and expression profile of LIMK1 in prostate tumors. Ectopic expression of LIMK1 in benign prostatic hyperplasia cells (BPH), which naturally express low levels of LIMK1, resulted in appearance of abnormal mitotic spindles, multiple centrosomes and smaller chromosomal masses. Furthermore, a transient G1/S phase arrest and delayed G2/M progression was observed in BPH cells expressing LIMK1. When treated with chemotherapeutic agent Taxol, no metaphase arrest was noted in these cells. We have also noted increased nuclear staining of LIMK1 in tumors with higher Gleason Scores and incidence of metastasis. Our results show that increased expression of LIMK1 results in chromosomal abnormalities, aberrant cell cycle progression and alteration of normal cellular response to microtubule stabilizing agent Taxol; and that LIMK1 expression may be associated with cancerous phenotype of the prostate.

Anoctamin 1 (TMEM16A) is essential for testosterone-induced prostate hyperplasia.

PubMed

Cha, Joo Young; Wee, Jungwon; Jung, Jooyoung; Jang, Yongwoo; Lee, Byeongjun; Hong, Gyu-Sang; Chang, Beom Chul; Choi, Yoon-La; Shin, Young Kee; Min, Hye-Young; Lee, Ho-Young; Na, Tae-Young; Lee, Mi-Ock; Oh, Uhtaek

2015-08-04

Benign prostatic hyperplasia (BPH) is characterized by an enlargement of the prostate, causing lower urinary tract symptoms in elderly men worldwide. However, the molecular mechanism underlying the pathogenesis of BPH is unclear. Anoctamin1 (ANO1) encodes a Ca(2+)-activated chloride channel (CaCC) that mediates various physiological functions. Here, we demonstrate that it is essential for testosterone-induced BPH. ANO1 was highly amplified in dihydrotestosterone (DHT)-treated prostate epithelial cells, whereas the selective knockdown of ANO1 inhibited DHT-induced cell proliferation. Three androgen-response elements were found in the ANO1 promoter region, which is relevant for the DHT-dependent induction of ANO1. Administration of the ANO1 blocker or Ano1 small interfering RNA, inhibited prostate enlargement and reduced histological abnormalities in vivo. We therefore concluded that ANO1 is essential for the development of prostate hyperplasia and is a potential target for the treatment of BPH.

Anoctamin 1 (TMEM16A) is essential for testosterone-induced prostate hyperplasia

PubMed Central

Cha, Joo Young; Wee, Jungwon; Jung, Jooyoung; Jang, Yongwoo; Lee, Byeongjun; Hong, Gyu-Sang; Chang, Beom Chul; Choi, Yoon-La; Shin, Young Kee; Min, Hye-Young; Lee, Ho-Young; Na, Tae-Young; Lee, Mi-Ock; Oh, Uhtaek

2015-01-01

Benign prostatic hyperplasia (BPH) is characterized by an enlargement of the prostate, causing lower urinary tract symptoms in elderly men worldwide. However, the molecular mechanism underlying the pathogenesis of BPH is unclear. Anoctamin1 (ANO1) encodes a Ca2+-activated chloride channel (CaCC) that mediates various physiological functions. Here, we demonstrate that it is essential for testosterone-induced BPH. ANO1 was highly amplified in dihydrotestosterone (DHT)-treated prostate epithelial cells, whereas the selective knockdown of ANO1 inhibited DHT-induced cell proliferation. Three androgen-response elements were found in the ANO1 promoter region, which is relevant for the DHT-dependent induction of ANO1. Administration of the ANO1 blocker or Ano1 small interfering RNA, inhibited prostate enlargement and reduced histological abnormalities in vivo. We therefore concluded that ANO1 is essential for the development of prostate hyperplasia and is a potential target for the treatment of BPH. PMID:26153424

Analysis of Thermally Denatured Depth in Laser Vaporization for Benign Prostatic Hyperplasia using a Simulation of Light Propagation and Heat Transfer (secondary publication)

PubMed Central

Takada, Junya; Honda, Norihiro; Hazama, Hisanao; Ioritani, Naomasa

2016-01-01

Background and Aims: Laser vaporization of the prostate is expected as a less invasive treatment for benign prostatic hyperplasia (BPH), via the photothermal effect. In order to develop safer and more effective laser vaporization of the prostate, it is essential to set optimal irradiation parameters based on quantitative evaluation of temperature distribution and thermally denatured depth in prostate tissue. Method: A simulation model was therefore devised with light propagation and heat transfer calculation, and the vaporized and thermally denatured depths were estimated by the simulation model. Results: The results of the simulation were compared with those of an ex vivo experiment and clinical trial. Based on the accumulated data, the vaporized depth strongly depended on the distance between the optical fiber and the prostate tissue, and it was suggested that contact laser irradiation could vaporize the prostate tissue most effectively. Additionally, it was suggested by analyzing thermally denatured depth comprehensively that laser irradiation at the distance of 3 mm between the optical fiber and the prostate tissue was useful for hemostasis. Conclusions: This study enabled quantitative and reproducible analysis of laser vaporization for BPH and will play a role in clarification of the safety and efficacy of this treatment. PMID:28765672

Prognostic Value of Abnormal p53 Expression in Locally Advanced Prostate Cancer Treated With Androgen Deprivation and Radiotherapy: A Study Based on RTOG 9202

DOE Office of Scientific and Technical Information (OSTI.GOV)

Che Mingxin; DeSilvio, Michelle; Pollack, Alan

2007-11-15

Purpose: The goal of this study was to verify the significance of p53 as a prognostic factor in Radiation Therapy Oncology Group 9202, which compared short-term androgen deprivation (STAD) with radiation therapy (RT) to long-term androgen deprivation + RT in men with locally advanced prostate cancer (Pca). Methods and Materials: Tumor tissue was sufficient for p53 analysis in 777 cases. p53 status was determined by immunohistochemistry. Abnormal p53 expression was defined as 20% or more tumor cells with positive nuclei. Univariate and multivariate Cox proportional hazards models were used to evaluate the relationships of p53 status to patient outcomes. Results:more » Abnormal p53 was detected in 168 of 777 (21.6%) cases, and was significantly associated with cause-specific mortality (adjusted hazard ratio [HR] = 1.89; 95% confidence interval (CI) 1.14 - 3.14; p = 0.014) and distant metastasis (adjusted HR = 1.72; 95% CI 1.13-2.62; p = 0.013). When patients were divided into subgroups according to assigned treatment, only the subgroup of patients who underwent STAD + RT showed significant correlation between p53 status and cause-specific mortality (adjusted HR = 2.43; 95% CI = 1.32-4.49; p = 0.0044). When patients were divided into subgroups according to p53 status, only the subgroup of patients with abnormal p53 showed significant association between assigned treatment and cause-specific mortality (adjusted HR = 3.81; 95% CI 1.40-10.37; p = 0.0087). Conclusions: Abnormal p53 is a significant prognostic factor for patients with prostate cancer who undergo short-term androgen deprivation and radiotherapy. Long-term androgen deprivation may significantly improve the cause-specific survival for those with abnormal p53.« less

PREDICTIVE SIMULATION MODELING FOR ANTIANDROGEN IMPACTS ON RODENT PROSTATE

EPA Science Inventory

Predictive simulation modeling for antiandrogen impacts on rodent prostate
HA Barton1, RW Setzer1, LK Potter1,2
1US EPA, ORD, NHEERL, ETD, PKB, Research Triangle Park, NC and 2Curriculum in Toxicology, UNC, Chapel Hill, NC

Changes in rodent prostate weight and functi...

Cancer telomeres and white crows.

PubMed

Meeker, Alan K

2018-01-01

This mini-review article discusses past and present prostate-focused research on telomere and telomerase biology conducted at Johns Hopkins, through the eyes of a Donald S Coffey trainee. Included are past discoveries of abnormalities in telomere biology in the context of prostate cancer and its pre-malignant precursor prostatic intraepithelial neoplasia (PIN); the finding that telomerase activity is androgen-regulated in the prostate, and the potential role of telomerase in prostate epithelial stem cells. Also reviewed are more recent results showing that in situ telomere length measurements in patient tissue specimens may have utility in risk assessment and as a prognostic biomarker. Highlighted throughout the article are some of the training and mentorship approaches employed by the late Dr. Coffey, former Director of Urologic Research at the Brady Urological Research Institute, which inspired new research ideas, team science, and discovery.

DEVELOPING A PREDICTIVE SIMULATION MODEL FOR ANTIANDROGEN IMPACTS ON RODENT PROSTATE

EPA Science Inventory

Developing a predictive simulation model for antiandrogen impacts on rodent prostate
HA Barton1, RW Setzer1, LK Potter1,2
1US EPA, ORD, NHEERL, ETD, PKB, Research Triangle Park, NC and 2Curriculum in Toxicology, UNC, Chapel Hill, NC

Alterations in rodent prostate wei...

Simulating intrafraction prostate motion with a random walk model.

PubMed

Pommer, Tobias; Oh, Jung Hun; Munck Af Rosenschöld, Per; Deasy, Joseph O

2017-01-01

Prostate motion during radiation therapy (ie, intrafraction motion) can cause unwanted loss of radiation dose to the prostate and increased dose to the surrounding organs at risk. A compact but general statistical description of this motion could be useful for simulation of radiation therapy delivery or margin calculations. We investigated whether prostate motion could be modeled with a random walk model. Prostate motion recorded during 548 radiation therapy fractions in 17 patients was analyzed and used for input in a random walk prostate motion model. The recorded motion was categorized on the basis of whether any transient excursions (ie, rapid prostate motion in the anterior and superior direction followed by a return) occurred in the trace and transient motion. This was separately modeled as a large step in the anterior/superior direction followed by a returning large step. Random walk simulations were conducted with and without added artificial transient motion using either motion data from all observed traces or only traces without transient excursions as model input, respectively. A general estimate of motion was derived with reasonable agreement between simulated and observed traces, especially during the first 5 minutes of the excursion-free simulations. Simulated and observed diffusion coefficients agreed within 0.03, 0.2 and 0.3 mm 2 /min in the left/right, superior/inferior, and anterior/posterior directions, respectively. A rapid increase in variance at the start of observed traces was difficult to reproduce and seemed to represent the patient's need to adjust before treatment. This could be estimated somewhat using artificial transient motion. Random walk modeling is feasible and recreated the characteristics of the observed prostate motion. Introducing artificial transient motion did not improve the overall agreement, although the first 30 seconds of the traces were better reproduced. The model provides a simple estimate of prostate motion during delivery of radiation therapy.

Smooth muscle cell-specific knockout of androgen receptor: a new model for prostatic disease.

PubMed

Welsh, Michelle; Moffat, Lindsey; McNeilly, Alan; Brownstein, David; Saunders, Philippa T K; Sharpe, Richard M; Smith, Lee B

2011-09-01

Androgen-driven stromal-epithelial interactions play a key role in normal prostate development and function as well as in the progression of common prostatic diseases such as benign prostatic hyperplasia and prostate cancer. However, exactly how, and via which cell type, androgens mediate their effects in the adult prostate remains unclear. This study investigated the role for smooth muscle (SM) androgen signaling in normal adult prostate homeostasis and function using mice in which androgen receptor was selectively ablated from prostatic SM cells. In adulthood the knockout (KO) mice displayed a 44% reduction in prostate weight and exhibited histological abnormalities such as hyperplasia, inflammation, fibrosis, and reduced expression of epithelial, SM, and stem cell identify markers (e.g. p63 reduced by 27% and Pten by 31%). These changes emerged beyond puberty and were not explained by changes in serum hormones. Furthermore, in response to exogenous estradiol, adult KO mice displayed an 8.5-fold greater increase in prostate weight than controls and developed urinary retention. KO mice also demonstrated a reduced response to castration compared with controls. Together these results demonstrate that prostate SM cells are vital in mediating androgen-driven stromal-epithelial interactions in adult mouse prostates, determining cell identity and function and limiting hormone-dependent epithelial cell proliferation. This novel mouse model provides new insight into the possible role for SM androgen action in prostate disease.

Lessons Learned from Implementing a Prostate Cancer Risk Assessment Program for Underserved High-Risk Men in the Community: the Prostate REACH Project.

PubMed

Fleisher, Linda; Davis, Stacy N; Gross, Laura; Bagden, Loretta; Zakrzewski, Debra; González, Evelyn; Kandadai, Venk; Rusten, Cheryl; Baskett, Jerilyn; Obeid, Elias; Giri, Veda N

2016-03-01

Prostate cancer disproportionately affects Black men, who may also encounter barriers to participation in prostate cancer risk assessment. The Prostate Risk, Education and Assessment in the Community with Help (REACH) project was a community-based extension of a comprehensive prostate cancer risk assessment program at a comprehensive cancer center. The goals of the REACH project were the following: (1) establish a community prostate cancer risk assessment clinic, (2) conduct targeted recruitment, and (3) provide navigation services including follow-up for uninsured men. Key implementation steps included the following: (1) choosing a clinic site, (2) establishing patient access procedures, (3) establishing navigator services, (4) developing subsidy fund use guidelines, and (5) designing recruitment and promotion. Through community-based promotion, 64 men inquired about the program and 26 (41 %) participated. Of those screened, 46 % had abnormal results, and 2 men were diagnosed with prostate cancer. Here, we describe a unique demonstration project to implement a comprehensive prostate cancer risk assessment program in an underserved Black community and describe successes and challenges to inform future efforts to promote access to underserved men.

Does imprint cytology improve the accuracy of transrectal prostate needle biopsy?

PubMed

Sayar, Hamide; Bulut, Burak Besir; Bahar, Abdulkadir Yasir; Bahar, Mustafa Remzi; Seringec, Nurten; Resim, Sefa; Çıralık, Harun

2015-02-01

To evaluate the accuracy of imprint cytology of core needle biopsy specimens in the diagnosis of prostate cancer. Between December 24, 2011 and May 9, 2013, patients with an abnormal DRE and/or serum PSA level of >2.5 ng/mL underwent transrectal prostate needle biopsy. Samples with positive imprint cytology but negative initial histologic exam underwent repeat sectioning and histological examination. 1,262 transrectal prostate needle biopsy specimens were evaluated from 100 patients. Malignant imprint cytology was found in 236 specimens (18.7%), 197 (15.6%) of which were confirmed by histologic examination, giving an initial 3.1% (n = 39) rate of discrepant results by imprint cytology. Upon repeat sectioning and histologic examination of these 39 biopsy samples, 14 (1.1% of the original specimens) were then diagnosed as malignant, 3 (0.2%) as atypical small acinar proliferation (ASAP), and 5 (0.4%) as high-grade prostatic intraepithelial neoplasia (HGPIN). Overall, 964 (76.4%) specimens were negative for malignancy by imprint cytology. Seven (0.6%) specimens were benign by cytology but malignant cells were found on histological evaluation. On imprint cytology examination, nonmalignant but abnormal findings were seen in 62 specimens (4.9%). These were all due to benign processes. After reexamination, the accuracy, sensitivity, specificity, positive predictive value, negative predictive value, false-positive rate, false-negative rate of imprint preparations were 98.1, 96.9, 98.4, 92.8, 99.3, 1.6, 3.1%, respectively. Imprint cytology is valuable tool for evaluating TRUS-guided core needle biopsy specimens from the prostate. Use of imprint cytology in combination with histopathology increases diagnostic accuracy when compared with histopathologic assessment alone. © 2014 Wiley Periodicals, Inc.

Careful assessment key in managing prostatitis.

PubMed

Gujadhur, Rahul; Aning, Jonathan

2015-04-01

Prostatitis is a common condition estimated to affect up to 30% of men in their lifetime, it is most prevalent in men aged between 35 and 50. Prostatitis is subclassified into: acute bacterial prostatitis, chronic bacterial prostatitis, chronic pelvic pain and asymptomatic inflammatory prostatitis. Acute bacterial prostatitis presents with acute onset pelvic pain which may or may not be related to voiding, lower urinary tract symptoms, sometimes haematuria or haematospermia and systemic symptoms such as fever and rigors. A documented history of recurrent urinary tract infections is the key feature of chronic bacterial prostatitis. Duration of symptoms > 3 months defines chronicity. The key symptom of chronic pelvic pain syndrome is pain. Patients may describe pain during or after ejaculation as their predominant symptom. Clinical assessment includes a thorough history and examination. A digital rectal examination should be performed after a midstream urine (MSU) sample has been collected for urine dipstick, microscopy and culture. The prostate should be checked for nodules. In acute bacterial prostatitis the MSU is the only laboratory investigation required. Chronic pelvic pain syndrome may be multifactorial and part of a more generalised pain disorder. Pelvic floor muscle abnormalities, altered neuroendocrine pathways, chemically induced inflammation, bacterial infection, autoimmune processes, dysfunctional voiding as well intraprostatic ductal reflux mechanisms have all been identified in men with chronic pelvic pain syndrome.

The epigenome as a therapeutic target in prostate cancer.

PubMed

Perry, Antoinette S; Watson, R William G; Lawler, Mark; Hollywood, Donal

2010-12-01

During cancer development and progression, tumor cells undergo abnormal epigenetic modifications, including DNA methylation, histone deacetylation and nucleosome remodeling. Collectively, these aberrations promote genomic instability and lead to silencing of tumor-suppressor genes and reactivation of oncogenic retroviruses. Epigenetic modifications, therefore, provide exciting new avenues for prostate cancer research. Promoter hypermethylation is widespread during neoplastic transformation of prostate cells, which suggests that restoration of a 'normal' epigenome through treatment with inhibitors of the enzymes involved could be clinically beneficial. Global patterns of histone modifications are also being defined and have been associated with clinical and pathologic predictors of prostate cancer outcome. Although treatment for localized prostate cancer can be curative, the development of successful therapies for the management of castration-resistant metastatic disease is urgently needed. Reactivation of tumor-suppressor genes by demethylating agents and histone deacetylase inhibitors could be a potential treatment option for patients with advanced disease.

Detecting prostate cancer and prostatic calcifications using advanced magnetic resonance imaging

PubMed Central

Dou, Shewei; Bai, Yan; Shandil, Ankit; Ding, Degang; Shi, Dapeng; Haacke, E Mark; Wang, Meiyun

2017-01-01

Prostate cancer and prostatic calcifications have a high incidence in elderly men. We aimed to investigate the diagnostic capabilities of susceptibility-weighted imaging in detecting prostate cancer and prostatic calcifications. A total number of 156 men, including 34 with prostate cancer and 122 with benign prostate were enrolled in this study. Computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging, and susceptibility-weighted imaging were performed on all the patients. One hundred and twelve prostatic calcifications were detected in 87 patients. The sensitivities and specificities of the conventional magnetic resonance imaging, apparent diffusion coefficient, and susceptibility-filtered phase images in detecting prostate cancer and prostatic calcifications were calculated. McNemar's Chi-square test was used to compare the differences in sensitivities and specificities between the techniques. The results showed that the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic cancer were greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). In addition, the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic calcifications were comparable to that of computed tomography and greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). Given the high incidence of susceptibility-weighted imaging (SWI) abnormality in prostate cancer, we conclude that susceptibility-weighted imaging is more sensitive and specific than conventional magnetic resonance imaging, diffusion-weighted imaging, and computed tomography in detecting prostate cancer. Furthermore, susceptibility-weighted imaging can identify prostatic calcifications similar to computed tomography, and it is much better than conventional magnetic resonance imaging and diffusion-weighted imaging. PMID:27004542

Detecting prostate cancer and prostatic calcifications using advanced magnetic resonance imaging.

PubMed

Dou, Shewei; Bai, Yan; Shandil, Ankit; Ding, Degang; Shi, Dapeng; Haacke, E Mark; Wang, Meiyun

2017-01-01

Prostate cancer and prostatic calcifications have a high incidence in elderly men. We aimed to investigate the diagnostic capabilities of susceptibility-weighted imaging in detecting prostate cancer and prostatic calcifications. A total number of 156 men, including 34 with prostate cancer and 122 with benign prostate were enrolled in this study. Computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging, and susceptibility-weighted imaging were performed on all the patients. One hundred and twelve prostatic calcifications were detected in 87 patients. The sensitivities and specificities of the conventional magnetic resonance imaging, apparent diffusion coefficient, and susceptibility-filtered phase images in detecting prostate cancer and prostatic calcifications were calculated. McNemar's Chi-square test was used to compare the differences in sensitivities and specificities between the techniques. The results showed that the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic cancer were greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). In addition, the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic calcifications were comparable to that of computed tomography and greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). Given the high incidence of susceptibility-weighted imaging (SWI) abnormality in prostate cancer, we conclude that susceptibility-weighted imaging is more sensitive and specific than conventional magnetic resonance imaging, diffusion-weighted imaging, and computed tomography in detecting prostate cancer. Furthermore, susceptibility-weighted imaging can identify prostatic calcifications similar to computed tomography, and it is much better than conventional magnetic resonance imaging and diffusion-weighted imaging.

Goserelin Implant

MedlinePlus

Goserelin implant is used in combination with radiation therapy and other medications to treat localized prostate cancer ... and other symptoms) and to help with the treatment of abnormal bleeding of the uterus. Goserelin implant ...

Being screened for prostate cancer: a simple blood test or a commitment to treatment?

PubMed

Oliffe, John

2006-01-01

The virtues of screening men for prostate cancer continue to be debated in political and public health, as well as clinical forums. Science has been unable to accurately predict screening benefits, yet many men are required to make informed decisions about prostate cancer screening. Clinicians' screening practices have been reported, but little research attention has been given to patients' experiences. The purpose of this study was to describe patients' perspectives of being screened and subsequently diagnosed with prostate cancer. Thirty-five Anglo-Australian men were interviewed, and the data were analyzed using ethnographic content analysis. The findings indicated that most participants experienced screening as a continuum of 3 tests, rather than the simple prostate-specific antigen blood test they had often anticipated. Commitment to a definitive diagnosis when abnormality was detected through screening and uptake of active treatment(s) when prostate cancer was confirmed were strongly represented in this study. The findings offer insight to the complex and often rapid sequence of events that can accompany prostate cancer screening. This has implications for the information that needs to be discussed with men before, rather than after prostate cancer screening has commenced.

Prostate cancer diagnosis in a resource-poor setting: the changing role of digital rectal examination.

PubMed

Ahmed, Muhammed

2011-07-01

We undertook this study in order to determine the current role of digital rectal examination (DRE) in the diagnosis of prostate cancer in a resource-poor setting. The diagnosis of prostate cancer has been revolutionized by the introduction of prostate-specific antigen (PSA), transrectal ultrasound (TRUS) for biopsy guidance and more efficient biopsy equipment, but they are not readily available in most developing countries. This is a prospective study of 131 patients with suspected prostate cancer based on clinical presentation, DRE and elevated PSA. The presence or absence of cancer was confirmed by biopsy and histologic examination. Patients with screen- or incidentally-detected prostate cancer were excluded. The most common symptom was the development of lower urinary tract symptoms (LUTS). All patients had abnormal DRE and indurated prostate was the most frequent finding (50%). The mean PSA was 33.9 ng/mL: of the 131 patients, 80 (61.1%) had a malignant histology following biopsy, 47 (35.9%) were benign and four (3.0%) were prostate intraepithelial neoplasia (PIN). The low specificity of DRE in the diagnosis of prostate cancer requires that it should be combined with other diagnostic modalities such as PSA and TRUS-guided prostate biopsy. Thus government and health-care providers in resource-poor countries must strive to make these facilities available in order to improve prostate cancer diagnosis.

Comparison between target magnetic resonance imaging (MRI) in-gantry and cognitively directed transperineal or transrectal-guided prostate biopsies for Prostate Imaging-Reporting and Data System (PI-RADS) 3-5 MRI lesions.

PubMed

Yaxley, Anna J; Yaxley, John W; Thangasamy, Isaac A; Ballard, Emma; Pokorny, Morgan R

2017-11-01

To compare the detection rates of prostate cancer (PCa) in men with Prostate Imaging-Reporting and Data System (PI-RADS) 3-5 abnormalities on 3-Tesla multiparametric (mp) magnetic resonance imaging (MRI) using in-bore MRI-guided biopsy compared with cognitively directed transperineal (cTP) biopsy and transrectal ultrasonography (cTRUS) biopsy. This was a retrospective single-centre study of consecutive men attending the private practice clinic of an experienced urologist performing MRI-guided biopsy and an experienced urologist performing cTP and cTRUS biopsy techniques for PI-RADS 3-5 lesions identified on 3-Tesla mpMRI. There were 595 target mpMRI lesions from 482 men with PI-RADS 3-5 regions of interest during 483 episodes of biopsy. The abnormal mpMRI target lesion was biopsied using the MRI-guided method for 298 biopsies, the cTP method for 248 biopsies and the cTRUS method for 49 biopsies. There were no significant differences in PCa detection among the three biopsy methods in PI-RADS 3 (48.9%, 40.0% and 44.4%, respectively), PI-RADS 4 (73.2%, 81.0% and 85.0%, respectively) or PI-RADS 5 (95.2, 92.0% and 95.0%, respectively) lesions, and there was no significant difference in detection of significant PCa among the biopsy methods in PI-RADS 3 (42.2%, 30.0% and 33.3%, respectively), PI-RADS 4 (66.8%, 66.0% and 80.0%, respectively) or PI-RADS 5 (90.5%, 89.8% and 90.0%, respectively) lesions. There were also no differences in PCa or significant PCa detection based on lesion location or size among the methods. We found no significant difference in the ability to detect PCa or significant PCa using targeted MRI-guided, cTP or cTRUS biopsy methods. Identification of an abnormal area on mpMRI appears to be more important in increasing the detection of PCa than the technique used to biopsy an MRI abnormality. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Risk of Clinically Significant Prostate Cancer Associated With Prostate Imaging Reporting and Data System Category 3 (Equivocal) Lesions Identified on Multiparametric Prostate MRI.

PubMed

Sheridan, Alison D; Nath, Sameer K; Syed, Jamil S; Aneja, Sanjay; Sprenkle, Preston C; Weinreb, Jeffrey C; Spektor, Michael

2018-02-01

The objective of this study is to determine the frequency of clinically significant cancer (CSC) in Prostate Imaging Reporting and Data System (PI-RADS) category 3 (equivocal) lesions prospectively identified on multiparametric prostate MRI and to identify risk factors (RFs) for CSC that may aid in decision making. Between January 2015 and July 2016, a total of 977 consecutively seen men underwent multiparametric prostate MRI, and 342 underwent MRI-ultrasound (US) fusion targeted biopsy. A total of 474 lesions were retrospectively reviewed, and 111 were scored as PI-RADS category 3 and were visualized using a 3-T MRI scanner. Multiparametric prostate MR images were prospectively interpreted by body subspecialty radiologists trained to use PI-RADS version 2. CSC was defined as a Gleason score of at least 7 on targeted biopsy. A multivariate logistic regression model was constructed to identify the RFs associated with CSC. Of the 111 PI-RADS category 3 lesions, 81 (73.0%) were benign, 11 (9.9%) were clinically insignificant (Gleason score, 6), and 19 (17.1%) were clinically significant. On multivariate analysis, three RFs were identified as significant predictors of CSC: older patient age (odds ratio [OR], 1.13; p = 0.002), smaller prostate volume (OR, 0.94; p = 0.008), and abnormal digital rectal examination (DRE) findings (OR, 3.92; p = 0.03). For PI-RADS category 3 lesions associated with zero, one, two, or three RFs, the risk of CSC was 4%, 16%, 62%, and 100%, respectively. PI-RADS category 3 lesions for which two or more RFs were noted (e.g., age ≥ 70 years, gland size ≤ 36 mL, or abnormal DRE findings) had a CSC detection rate of 67% with a sensitivity of 53%, a specificity of 95%, a positive predictive value of 67%, and a negative predictive value of 91%. Incorporating clinical parameters into risk stratification algorithms may improve the ability to detect clinically significant disease among PI-RADS category 3 lesions and may aid in the decision to perform biopsy.

Is there a link between BPH and prostate cancer?

PubMed

Chang, R T M; Kirby, Roger; Challacombe, B J

2012-04-01

BPH is one of the most common diseases of older men, with more than 70% of men over 70 years affected, and prostate cancer is the most common cancer in men in the UK. Prostate cancer generally presents in one of three ways: asymptomatic patients who are screened (usually by a PSA test); men with LUTS who are investigated and undergo prostate biopsy; or patients with symptoms of metastasis such as bone pain. Men can be reassured that the main cause of LUTS is BPH. Only a small proportion of men have LUTS that are directly attributable to prostate cancer. Digital rectal examination (DRE) gives an evaluation of prostate size, which is relevant in particular to BPH management, and along with PSA testing it is one of the only ways of differentiating clinically between BPH and prostate cancer. If a nodular abnormality is present there is around a 50% chance of a diagnosis of prostate cancer being made on biopsy. Raised levels of serum PSA may be suggestive of prostate cancer, but diagnosis requires histological confirmation in almost every case. A normal PSA, PSA density and DRE can give reasonable confidence with regards to excluding clinically significant prostate cancer. BPH is not a known risk factor for prostate cancer, although the two frequently coexist. Age is the strongest predictor of prostate cancer risk, along with family history. BPH is not considered to be a precursor of prostate cancer. It is likely that although BPH may not make prostate cancer more likely to occur, it may increase the chance of diagnosing an incidental cancer.

Mechanisms of Abnormal Growth Regulation in Prostatic Adenocarcinoma Using Abi1/Hssh3bp1 Conditional Knockout Mouse Model

DTIC Science & Technology

2009-06-01

density lipoprotein uptake and cholesterol accumulation by macrophages differentiated from human monocytes with macrophage-colony-stimulating factor (M...model will likely have high impact on the prostate cancer research field including development of novel potential drug therapies. Our model will...Shin, and B.J. Mayer. 2007. High -throughput phosphotyrosine profiling using SH2 domains. Mol Cell. 26:899-915. Macoska, J.A., J. Xu, D. Ziemnicka, T.S

Mono or bilateral inflammatory postmicrobial prostato-vesciculo-epididymitis: differences in semen parameters and reactive oxygen species production.

PubMed

La Vignera, S; Calogero, A E; Cannizzaro, M A; Vicari, E

2006-12-01

The aim of this study was to analyse possible differences in sperm characteristics (including seminal leukocyte concentration, number of spermiophagies, and sperm reactive oxygen species [ROS] production) between patients with monolateral and bilateral prostate-vesciculo-epididymitis (PVE). Seventy-eight selected consecutively enrolled patients (mean age 34 years, range 24-40) with chronic inflammatory postmicrobial PVE and 30 infertile (aged-matched) patients (control group) with inflammatory postmicrobial prostatitis underwent sperm analysis, including seminal leukocyte concentration, number of spermiophages, and ROS production. Sperm concentration and total sperm number were significantly lower in the patients with bilateral PVE than in those with monolateral PVE. The percentage of cases with oligozoospermia or hyperspermia was significantly higher among patients with bilateral PVE with than those with monolateral PVE. Although the remaining cytologic and physicochemical sperm characteristics and ROS production (both in 45% and 90% Percoll fractions) were not significantly different between the 2 PVE groups, both groups showed median and relative percentages of frequency of abnormal sperm characteristics worse than those in the control group. Although sperm abnormalities (including seminal leukocyte concentration, number of spermiophages, and ROS production) can distinguish patients with PVE from those with prostatitis alone, the abnormalities did not discriminate between unilateral and bilateral PVE. In diagnostic suspicion of PVE, didymo-epididymal and prostato-vescicular ultrasonography can help discriminate monolateral from bilateral forms of PVE, and is a useful aid in the follow-up of these patients.

Retrospective review of clinical practice in chronic pelvic pain syndrome i.e. category III chronic prostatitis at two hospital sites over five years 2000-2005 (an audit).

PubMed

Evans, D T P; Jaleel, H; Keefe, A

2007-04-01

All category III chronic prostatitis cases in two hospital sites were retrospectively reviewed from the year 2000 until 2005. The mean age of the patients was 38.7 years. Of these, 56.6% were St Bartholomew's Genitourinary Medicine Department patients and 43.5% were Southend Genitourinary Medicine Clinic patients. We observed that 33.1% of these had at least one transrectal ultrasound of the prostate. The commonest abnormal findings in transrectal ultrasounds of the prostate of the series were focal calcification (16.2%), calculi (9.3%) and inflammatory changes (5.4%). Of this series, 35% were lost to follow-up. The vast majority of the remainder got better over periods ranging from approximately two weeks to approximately three years.

Clinical implications of prostate-specific antigen in men and women.

PubMed

Yu, H

2000-01-01

Prostate-specific antigen (PSA) is a valuable tumor marker for prostate cancer. Although it is indeed produced at an extremely high level by the prostate, PSA is also expressed in many female tissues, especially those regulated by sex steroid hormones. PSA is detected in both normal and abnormal breast tissue, as well as in various breast fluids, including milk, nipple aspirate, and cyst fluid. Clinical studies suggest that the presence of PSA in breast tissue may indicate a favorable prognosis for breast cancer patients. Levels of PSA in nipple aspirate fluid, however, may be indicative of breast cancer risk. Concentrations of PSA in serum are elevated in pregnant women as well as in women who have excess androgens. More studies are necessary to determine the clinical implications of the presence of PSA in amniotic fluid and female serum.

Monte Carlo investigation of I-125 interseed attenuation for standard and thinner seeds in prostate brachytherapy with phantom validation using a MOSFET.

PubMed

Mason, J; Al-Qaisieh, B; Bownes, P; Henry, A; Thwaites, D

2013-03-01

In permanent seed implant prostate brachytherapy the actual dose delivered to the patient may be less than that calculated by TG-43U1 due to interseed attenuation (ISA) and differences between prostate tissue composition and water. In this study the magnitude of the ISA effect is assessed in a phantom and in clinical prostate postimplant cases. Results are compared for seed models 6711 and 9011 with 0.8 and 0.5 mm diameters, respectively. A polymethyl methacrylate (PMMA) phantom was designed to perform ISA measurements in a simple eight-seed arrangement and at the center of an implant of 36 seeds. Monte Carlo (MC) simulation and experimental measurements using a MOSFET dosimeter were used to measure dose rate and the ISA effect. MC simulations of 15 CT-based postimplant prostate treatment plans were performed to compare the clinical impact of ISA on dose to prostate, urethra, rectum, and the volume enclosed by the 100% isodose, for 6711 and 9011 seed models. In the phantom, ISA reduced the dose rate at the MOSFET position by 8.6%-18.3% (6711) and 7.8%-16.7% (9011) depending on the measurement configuration. MOSFET measured dose rates agreed with MC simulation predictions within the MOSFET measurement uncertainty, which ranged from 5.5% to 7.2% depending on the measurement configuration (k = 1, for the mean of four measurements). For 15 clinical implants, the mean ISA effect for 6711 was to reduce prostate D90 by 4.2 Gy (3%), prostate V100 by 0.5 cc (1.4%), urethra D10 by 11.3 Gy (4.4%), rectal D2cc by 5.5 Gy (4.6%), and the 100% isodose volume by 2.3 cc. For the 9011 seed the mean ISA effect reduced prostate D90 by 2.2 Gy (1.6%), prostate V100 by 0.3 cc (0.7%), urethra D10 by 8.0 Gy (3.2%), rectal D2cc by 3.1 Gy (2.7%), and the 100% isodose volume by 1.2 cc. Differences between the MC simulation and TG-43U1 consensus data for the 6711 seed model had a similar impact, reducing mean prostate D90 by 6 Gy (4.2%) and V100 by 0.6 cc (1.8%). ISA causes the delivered dose in prostate seed implant brachytherapy to be lower than the dose calculated by TG-43U1. MC simulation of phantom seed arrangements show that dose at a point can be reduced by up to 18% and this has been validated using a MOSFET dosimeter. Clinical simulations show that ISA reduces DVH parameter values, but the reduction is less for thinner seeds.

[The role of a single PCA3 test before a first negative prostate biopsy: 5-year follow-up].

PubMed

Bernardeau, S; Charles, T; Fromont-Hankard, G; Irani, J

2017-04-01

We report a 5-year follow-up of a cohort of patients who underwent a first prostate biopsy following a prostate cancer antigen 3 (PCA3) test. We reviewed consecutive patients who had in 2008 a single urinary PCA3 test using the Gen-Probe ® assay before a first prostate biopsy for a prostate-specific antigen (PSA) between 3 and 20ng/mL and/or a suspicious digital rectal examination. PCA3 performances were analyzed in 2008 and then in 2013 after taking into account the results of repeat biopsies. At initial biopsy in 2008, among the 125 patients study cohort, prostate cancer was diagnosed in 47 patients (37.6%). Abnormal digital rectal exam, PSA density, prostate volume and PCA3 score were significantly associated with prostate cancer diagnosis. PCA3 area under the curve of the receiver operating curve was 0.67 [95%CI: 0.57-0.76] with an optimal threshold of PCA3 in this sample of 24 units. During the 5-year follow-up, among the 78 patients with a negative prostate biopsy in 2008, 23 (29.5%) had a repeat prostate biopsy of whom 14 were diagnosed with prostate cancer. PCA3 score measured in 2008 was associated with prostate cancer diagnosis (P=0.002). All 9 patients with a negative repeat prostate biopsy had a PCA3 score below the cut-off while this was the case in only 2 patients among the 14 with a positive repeat prostate biopsy. The results of a single PCA3 test before a first prostate biopsy seems to be a useful aid in deciding whether to perform a repeat biopsy. 4. Copyright © 2017. Published by Elsevier Masson SAS.

Evaluation of Genomic Instability in the Abnormal Prostate

DTIC Science & Technology

2006-12-01

array CGH maps copy number aberrations relative to the genome sequence by using arrays of BAC or cDNA clones as the hybridization target instead of...data produced from these analyses complicate the interpretation of results . For these reasons, and as outlined by Davies et al., 22 it is desirable...There have been numerous studies of these abnormalities and several techniques, including 9 chromosome painting, array CGH and SNP arrays , have

The Role of Polycomb Group Gene Bmi-1 in the Development of Prostate Cancer

DTIC Science & Technology

2011-09-01

new tricks. Cell Div. 2006 Jul 24;1:15. 17. Fu M, Wang C, Li Z, Sakamaki T, Pestell RG. Minireview: Cyclin D1: normal and abnormal functions... Pestell RG. Signal transduction mediated by cyclin D1: from mitogens to cell proliferation: a molecular target with therapeutic potential. Cancer...Datar 22 R, Cote R, Pestell R, Albanese C. ErbB-2 induces the cyclin D1 gene in prostate epithelial cells in vitro and in vivo. Cancer Res. 2007

Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non-Neoplastic Prostate Tissue

DTIC Science & Technology

2014-10-01

in rare cells. Also, we tested several methods for multiplex analyses of transcriptome and DNA methylation changes. Further, we have secured...11 4 Introduction: Each year in the U.S. more than a million men with an elevated serum PSA or abnormal digital rectal exam...selective enrichment of un-methylated DNA, a phenomena which has long been recognized as ‘ PCR bias’ 6. We proposed a simple modification to the RRBS

Precision Medicine and Men's Health.

PubMed

Mata, Douglas A; Katchi, Farhan M; Ramasamy, Ranjith

2017-07-01

Precision medicine can greatly benefit men's health by helping to prevent, diagnose, and treat prostate cancer, benign prostatic hyperplasia, infertility, hypogonadism, and erectile dysfunction. For example, precision medicine can facilitate the selection of men at high risk for prostate cancer for targeted prostate-specific antigen screening and chemoprevention administration, as well as assist in identifying men who are resistant to medical therapy for prostatic hyperplasia, who may instead require surgery. Precision medicine-trained clinicians can also let couples know whether their specific cause of infertility should be bypassed by sperm extraction and in vitro fertilization to prevent abnormalities in their offspring. Though precision medicine's role in the management of hypogonadism has yet to be defined, it could be used to identify biomarkers associated with individual patients' responses to treatment so that appropriate therapy can be prescribed. Last, precision medicine can improve erectile dysfunction treatment by identifying genetic polymorphisms that regulate response to medical therapies and by aiding in the selection of patients for further cardiovascular disease screening.

Fetal alcohol exposure increases susceptibility to carcinogenesis and promotes tumor progression in prostate gland.

PubMed

Sarkar, Dipak K

2015-01-01

The idea that exposure to adverse environmental conditions and lifestyle choices during pregnancy can result in fetal programming that underlies disease susceptibility in adulthood is now widely accepted. Fetal alcohol exposed offspring displays many behavioral and physiological abnormalities including neuroendocrine-immune functions, which often carry over into their adult life. Since the neuroendocrine-immune system plays an important role in controlling tumor surveillance, fetal alcohol exposed offspring can be vulnerable to develop cancer. Animal studies have recently showed increased cancer growth and progression in various tissues of fetal alcohol exposed offspring. I will detail in this chapter the recent evidence for increased prostate carcinogenesis in fetal alcohol exposed rats. I will also provide evidence for a role of excessive estrogenization during prostatic development in the increased incidence of prostatic carcinoma in these animals. Furthermore, I will discuss the additional possibility of the involvement of impaired stress regulation and resulting immune incompetence in the increased prostatic neoplasia in the fetal alcohol exposed offspring.

Prevalence and characteristics of prostate cancer among participants of a community-based screening in Nigeria using serum prostate specific antigen and digital rectal examination.

PubMed

Ikuerowo, Stephen Odunayo; Omisanjo, Olufunmilade Adefolarin; Bioku, Muftau Jimoh; Ajala, Michael Olawale; Mordi, Victor Patrick Nonyelim; Esho, Julius Olusanmi

2013-01-01

Prostate cancer (CaP) is the most commonly diagnosed cancer among Nigerian men but CaP screening is not a common practice. The true burden of the disease in Nigeria is not known. The study was aimed at studying the community burden of CaP in Lagos. During a community-based prostate cancer awareness program in 13 local government areas of Lagos, men aged >40 years had serum total PSA (tPSA) test and digital rectal examination (DRE). Those with abnormal DRE or tPSA >95th percentile of the cohort or both were selected for prostate biopsy (TRPB). 4172 men were screened and complete data was available for 4110 (98.5%). The mean age was 60.8 years. DRE was abnormal in 410 men and was significantly correlated with the age of the patient and tPSA (p<0.001). The tPSA ranged from 0 to 438.3 ng/ml with a median, mean and 95th percentile of 1.5, 2.5 and 10.0 ng/ml respectively. 341 out of the 438 (78%) men selected were subjected to TRBP. Forty-three men had histological diagnosis of CaP, giving an estimated prevalence rate of at least 1.046% or 1046 per 100,000 men of age ≥40. Only 11 (26%) had organ-confined disease while 17 (40%) had locally advanced disease and 15 (35%) men had metastatic disease. The majority of the men, 32 (74%) were reported to have Gleason's score of ≥7. The prevalence rate of CaP among men aged ≥40 years in Lagos is higher than previously reported in hospital-based study. Majority have advanced and high-grade disease.

Differential expression of cytokeratin mRNA and protein in normal prostate, prostatic intraepithelial neoplasia, and invasive carcinoma.

PubMed Central

Yang, Y.; Hao, J.; Liu, X.; Dalkin, B.; Nagle, R. B.

1997-01-01

The expression of cytokeratin (CK) mRNA for CK5, -8, -14, -16, and -19 was investigated in normal prostate, prostatic intraepithelial neoplasia (PIN) lesions, and invasive carcinoma using in situ hybridization. Protein localization was carried out in adjacent sections using immunohistochemistry and correlated with mRNA expression. Snap-frozen human prostate samples including 22 examples of normal glands, 20 cases of PIN lesions, and 12 cases of invasive carcinoma were examined. CK5 and -14 mRNA and protein were prominently expressed only in the basal cells of normal glands and PIN lesions. CK14 mRNA was absent in the luminal cells of the most of the PIN lesions but was seen at a low level in some PIN lesions. CK14 protein was not detected in any PIN lesion, suggesting that, if the cell that makes up the PIN lesions is derived from a basal cell, CK14 translation is depressed although a low level of CK14 mRNA may persist. CK8 mRNA and protein were constitutively expressed in all epithelia of normal and abnormal prostate tissues. CK19 mRNA and protein were persistently expressed in both basal and luminal cells of the tubular portion of normal glands as well as PIN lesions, but were expressed heterogeneously in both basal and luminal cells of normal alveoli. CK16 mRNA was expressed in a similar pattern as CK19, but CK16 protein was not detected either in normal or in abnormal prostate tissues. In conclusion, the expression of CK19 in PIN lesions is similar to its tubular expression and would support an origin of PIN lesions from this structure rather than the alveolar portion of the glands. The similar cytokeratin expression between PIN lesions and invasive carcinoma further supports the concept that PIN is a precursor lesion of invasive carcinoma. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:9033282

Immortalization of human prostate epithelial cells by HPV 16 E6/E7 open reading frames.

PubMed

Choo, C K; Ling, M T; Chan, K W; Tsao, S W; Zheng, Z; Zhang, D; Chan, L C; Wong, Y C

1999-08-01

The exact pathogenesis for prostate cancer is not known. Progress made in prostate cancer research has been slow, largely due to the lack of suitable in vitro models. Here, we report our work on the immortalization of a human prostate epithelial cell line and show that it can be used as a model to study prostate tumorigenesis. Replication-defective retrovirus harboring the human papillomavirus (HPV) type 16 E6 and E7 open reading frames was used to infect primary human prostate epithelial cells. Polymerase chain reaction, followed by Southern hybridization for the HPV 16 E6/E7, Western blot for prostatic acid phosphatase, telomeric repeat amplification protocol assay for telomerase activity, two-dimensional gels for cytokeratins, and cytogenetic analysis were undertaken to characterized the infected cells. The retrovirus-infected cell line, HPr-1, continued to grow in culture for more than 80 successive passages. Normal primary cells failed to proliferate after passage 6. HPr-1 cells bore close resemblance to normal primary prostate epithelial cells, both morphologically and biochemically. However, they possessed telomerase activity and proliferated indefinitely. Cytogenetic analysis of HPr-1 cells revealed a human male karyotype with clonal abnormalities and the appearance of multiple double minutes. The HPr-1 cells expressed prostatic acid phosphatase and cytokeratins K8 and K18, proving that they were prostate epithelial cells. They were benign in nude mice tumor formation and soft agar colony formation assay. The HPr-1 cell line is an in vitro representation of early prostate neoplastic progression. Copyright 1999 Wiley-Liss, Inc.

Does prolonged anti-inflammatory therapy reduce number of unnecessary repeat saturation prostate biopsy?

PubMed

Candiano, Giuseppe; Pepe, Pietro; Pietropaolo, Francesco; Aragona, Francesco

2013-06-24

The effect of a prolonged oral anti-inflammatory therapy on PSA values in patients with persistent abnormal PSA values after negative prostate biopsy (PBx) was evaluated. From September 2011 to September 2012, 70 patients (medi- an age 62 years), with persistent abnormal PSA values after negative extended PBx, were given an herbal extract with anti-inflammatory activity for 3 months (Lenidase®; 1 tablet daily constituted of baicalina, bromelina and escina). All patients were submitted to prostate biopsy for: abnormal DRE; PSA > 10 ng/mL, PSA values between 4.1-10 or 2.6-4 ng/mL with free/total PSA < 25% and < 20%, respectively. Three months after the end of anti-inflammato- ry therapy all patients were revaluated; indication for repeat saturation biopsy (SPBx) and detection rate for PCa were compared with those previously recorded in our Department using the same inclusions criteria for biopsy. Oral administration of Lenidase® was well tolerated and no side effects were observed; PSA values decreased in 54 (77.8%) out 70 patients with a median PSA reduction of 20.5% (from 8.8 to 7 ng/mL) and remained unchanged in 16 patients (22.2%); the repeat SPBx rate resulted significantly lower (22.8% vs 35.5%; p < 0.05) showing a superimposable detection rate for PCa (3 cases) in comparison with our previous data (18.7% vs 22%). In our preliminary data a prolonged oral anti-inflammatory therapy reduced PSA levels in patients with negative PBx and persistent suspicious for PCa decreasing the indication to perform repeat SPBx (about 30% of the cases).

Sonoelastographic evaluation with the determination of compressibility ratio for symmetrical prostatic regions in the diagnosis of clinically significant prostate cancer

PubMed Central

Słapa, Rafał Z.; Jakubowski, Wiesław S.; Migda, Bartosz; Dmowski, Tadeusz

2014-01-01

Aim Sonoelastography is a technique that assesses tissue hardness/compressibility. Utility and sensitivity of the method in prostate cancer diagnostics were assessed compared to the current gold standard in prostate cancer diagnostics i.e. systematic biopsy. Material and methods The study involved 84 patients suspected of prostate cancer based on elevated PSA levels or abnormal per rectal examination findings. Sonoelastography was used to evaluate the prostate gland. In the case of regions with hardness two-fold greater than that of symmetric prostate area (strain ratio >2), targeted biopsy was used; which was followed by an ultrasound-guided 8- or 10-core systematic biopsy (regardless of sonoelastography-indicated sites) as a reference point. Results The mean age of patients was 69 years. PSA serum levels ranged between 1.02 and 885 ng/dl. The mean prostate volume was 62 ml (19–149 ml). Prostate cancer was found in 39 out of 84 individuals. Statistically significant differences in strain ratios between cancers and benign lesions were shown. Sonoelastography guided biopsy revealed 30 lesions – overall sensitivity 77% (sensitivity of the method – 81%). Sonoelastographic sensitivity increased depending on cancer stage according to the Gleason grading system: 6–60%, 7–75%, 8–83%, 9/10–100%. The estimated sensitivity of systematic biopsy was 92%. Conclusions Sonoelastography shows higher diagnostic sensitivity in prostate cancer diagnostics compared to conventional imaging techniques, i.e. grey-scale TRUS, Doppler ultrasound. It allows to reduce the number of collected tissue cores, and thus limit the incidence of complications as well as the costs involved. Sonoelastography using the determination of compressibility ratio for symmetrical prostatic regions may prove useful in the detection of clinically significant prostate cancer. PMID:26674065

Association between HIV status and Positive Prostate Biopsy in a Study of U.S. Veterans

PubMed Central

Hsiao, Wayland; Anastasia, Katrina; Hall, John; Goodman, Michael; Rimland, David; Ritenour, Chad W. M.; Issa, Muta M.

2009-01-01

HIV infection is associated with increased incidence of malignancies, such as lymphomas and testicular cancers. We reviewed the relationship between HIV infection and prostate cancer in a contemporary series of prostate biopsy patients. The study is a retrospective analysis of consecutive prostate biopsies performed at a VA Medical Center. The indications for performing a prostate biopsy included an abnormal digital rectal examination and/or an elevated PSA. Patients were categorized according to their HIV status, biopsy results, and various demographic and clinical characteristics. Univariate and multivariate analyses compared distributions of HIV status, and various clinical and demographic characteristics. The adjusted measures of association between HIV status and positive biopsy were expressed as odds ratios (ORs) and corresponding 95% confidence intervals (CI). The likelihood of positive biopsy was significantly higher among 18 HIV-positive patients compared to patients with negative HIV tests (adjusted OR = 3.9; 95% CI: 1.3–11.5). In analyses restricted to prostate cancer patients, HIV-positive patients were not different from the remaining group with respect to their prostate cancer stage, PSA level, PSA velocity, PSA density, or Gleason grade. There is an association between HIV infection and prostate biopsy positive for carcinoma in a population referred for urologic workup. Further confirmation of this association by prospective studies may impact the current screening practices in HIV patients. PMID:19219374

Theoretical Analysis of the Accuracy and Safety of MRI-Guided Transurethral 3-D Conformal Ultrasound Prostate Therapy

NASA Astrophysics Data System (ADS)

Burtnyk, Mathieu; Chopra, Rajiv; Bronskill, Michael

2009-04-01

MRI-guided transurethral ultrasound therapy is a promising new approach for the treatment of localized prostate cancer. Several studies have demonstrated the feasibility of producing large regions of thermal coagulation adequate for prostate therapy; however, the quantitative assessment of shaping these regions to complex 3-D human prostate geometries has not been fully explored. This study used numerical simulations and twenty manually-segmented pelvic anatomical models derived from high-quality MR images of prostate cancer patients to evaluate the treatment accuracy and safety of 3-D conformal MRI-guided transurethral ultrasound therapy. The simulations incorporated a rotating multi-element planar dual-frequency ultrasound transducer (seventeen 4×3 mm elements) operating at 4.7/9.7 MHz and 10 W/cm2 maximum acoustic power. Results using a novel feedback control algorithm which modulated the ultrasound frequency, power and device rate of rotation showed that regions of thermal coagulation could be shaped to predefined prostate volumes within 1.0 mm across the vast majority of these glands. Treatment times were typically 30 min and remained below 60 min for large 60 cc prostates. With a rectal cooling temperature of 15° C, the rectal wall did not exceed 30EM43 in half of the twenty patient models with only a few 1 mm3 voxels above this threshold in the other cases. At 4.7 MHz, heating of the pelvic bone can become significant when it is located less than 10 mm from the prostate. Numerical simulations show that MRI-guided transurethral ultrasound therapy can thermally coagulate whole prostate glands accurately and safely in 3-D.

Prostate histotripsy for BPH: initial canine results

NASA Astrophysics Data System (ADS)

Roberts, William W.; Hall, Timothy L.; Hempel, Christopher R.; Cain, Charles A.

2009-02-01

Histotripsy is an extracorporeal ablative technology that utilizes microsecond pulses of intense ultrasound (< 1% duty cycle) to produce nonthermal, mechanical fractionation of targeted tissue. We have previously demonstrated the feasibility of histotripsy prostate ablation. In this study we sought to assess the chronic tissue response, tolerability and safety of histotripsy in a chronic in vivo canine model. Five acute and thirteen chronic canine subjects were anesthetized and treated with histotripsy targeting the prostate. Pulses consisted of 3 cycle bursts of 750 kHz ultrasound at a repetition rate of 300 Hz delivered transabdominally from a highly focused 15 cm aperture array. Transrectal ultrasound imaging provided accurate targeting and real-time monitoring of histotripsy treatment. Prostates were harvested at 0, 7, 28, or 56 days after treatment. Consistent mechanical tissue fractionation and debulking of prostate tissue was seen acutely and at delayed time points without collateral injury. Urothelialization of the treatment cavity was apparent 28 days after treatment. Canine subjects tolerated histotripsy with minimal hematuria or discomfort. Only mild transient lab abnormalities were noted. Histotripsy is a promising non-invasive therapy for prostate tissue fractionation and debulking that appears safe and well tolerated without systemic side effects in the canine model.

Laboratory evaluations of erectile dysfunction: an evidence based approach.

PubMed

Bodie, Joshua; Lewis, Jean; Schow, Doug; Monga, Manoj

2003-06-01

We evaluate the prevalence of laboratory abnormalities in men presenting for initial evaluation and therapy of erectile dysfunction. The computerized charts of men receiving treatment for erectile dysfunction from 1987 to 2002 were retrospectively reviewed. We pooled laboratory data for 3,547 men with erectile dysfunction to assess the prevalence of laboratory abnormalities. Values of the common laboratory screening tests for erectile dysfunction were recorded for testosterone, prolactin, luteinizing hormone, thyroid-stimulating hormone, hemoglobin A(Ic), prostate specific antigen, hemoglobin, cholesterol and creatinine. Of those patients evaluated 18.7% had low testosterone, 4.6% had increased prolactin, 14.6% had abnormal luteinizing hormone, 4.0% had increased thyroid-stimulating hormone, 8.3% had increased prostate specific antigen, 26.5% had anemia and 11.9% tested had renal insufficiency. A high percentage of patients presenting with a primary complaint of erectile dysfunction had increased hemoglobin A(Ic) and total serum cholesterol levels (52.9% and 48.4%, respectively). An evidence based approach to standardization of laboratory evaluations for men presenting with erectile dysfunction is recommended. Laboratory screening should be directed to identify those risk factors that may benefit from lifestyle modification and pharmacological intervention.

The Role of Polycomb Group Gene BMI-1 in the Development of Prostate Cancer

DTIC Science & Technology

2010-09-01

2006 Jul 24;1:15. 17. Fu M, Wang C, Li Z, Sakamaki T, Pestell RG. Minireview: Cyclin D1: normal and abnormal functions. Endocrinology. 2004 Dec;145...and cyclin D1:connecting development to breast cancer. Cell Cycle. 2004 Feb;3(2):145-8. 32. Wang C, Li Z, Fu M, Bouras T, Pestell RG. Signal... Pestell R, Albanese C. ErbB-2 induces the cyclin D1 gene in prostate epithelial cells in vitro and in vivo. Cancer Res. 2007 May 1;67(9):4364-72. 36

Prostate-specific Antigen (PSA) Density and Free to Total PSA Ratio in Diagnosing Prostate Cancer with Prostate-Specific Antigen Levels of 4.0 ng/ml or Less.

PubMed

Liu, Xin; Tang, Jie; Fei, Xiang; Li, Qiu-Yang

2015-11-01

We aimed to value the usefulness of free to total prostate-specific antigen and Prostate-specific antigen (PSA) density for prostate cancer in the patients with PSA levels of 4.0 ng/ml or less. A total of 343 subjects with PSA levels of 4.0 ng/ml or less were biopsied. All patients were divided into four groups according to the PSA levels: 0 to 1.0 ng/ml, 1.1 to 2.0 ng/ml, 2.1 to 3.0 ng/ml, and 3.1 to 4.0 ng/ml. The reliability of cancer detection in relation to the f/t PSA ratio and PSAD were estimated. Overall, 65 people were diagnosed with prostate cancer. The detection rate was 16.28%、17.17%, 21.82%, 25.00% in subjects with PSA levels of 0 to 1.0 ng/ml, 1.1 to 2.0 ng/ml, 2.1 to 3.0 ng/ml, and 3.1 to 4.0 ng/ml, respectively. The f/t PSA ratio was significantly lower in patients with prostate cancer and PSA levels of 2.1 to 4.0 ng/ml (P<0.05). The PSAD had no statistical significance between the two groups. Routine prostate biopsy should be undertaken if the f/t PSA ratio less than 15% with /without abnormal DRE/TRUS findings.

Method of constructing a microwave antenna

NASA Technical Reports Server (NTRS)

Ngo, Phong (Inventor); Arndt, G. Dickey (Inventor); Carl, James (Inventor)

2003-01-01

A method, simulation, and apparatus are provided that are highly suitable for treatment of benign prostatic hyperplasia (BPH). A catheter is disclosed that includes a small diameter disk loaded monopole antenna surrounded by fusion material having a high heat of fusion and a melting point preferably at or near body temperature. Microwaves from the antenna heat prostatic tissue to promote necrosing of the prostatic tissue that relieves the pressure of the prostatic tissue against the urethra as the body reabsorbs the necrosed or dead tissue. The fusion material keeps the urethra cool by means of the heat of fusion of the fusion material. This prevents damage to the urethra while the prostatic tissue is necrosed. A computer simulation is provided that can be used to predict the resulting temperature profile produced in the prostatic tissue. By changing the various control features of the catheter and method of applying microwave energy a temperature profile can be predicted and produced that is similar to the temperature profile desired for the particular patient.

Method of Constructing a Microwave Antenna

NASA Technical Reports Server (NTRS)

Arndt, G. Dickey (Inventor); Carl, James (Inventor); Ngo, Phong (Inventor)

2003-01-01

A method, simulation, and apparatus are provided that are highly suitable for treatment of benign prostatic hyperplasia (BPH). A catheter is disclosed that includes a small diameter disk loaded monopole antenna surrounded by fusion material having a high heat of fusion and a melting point preferably at or near body temperature. Microwaves from the antenna heat prostatic tissue to promote necrosing of the prostatic tissue that relieves the pressure of the prostatic tissue against the urethra as the body reabsorbs the necrosed or dead tissue. The fusion material keeps the urethra cool by means of the heat of fusion of the fusion material. This prevents damage to the urethra while the prostatic tissue is necrosed. A computer simulation is provided that can be used to predict the resulting temperature profile produced in the prostatic tissue. By changing the various control features of the catheter and method of applying microwave energy a temperature profile can be predicted and produced that is similar to the temperature profile desired for the particular patient.

Method for selective thermal ablation

NASA Technical Reports Server (NTRS)

Ngo, Phong (Inventor); Arndt, G. Dickey (Inventor); Raffoul, George W. (Inventor); Carl, James (Inventor)

2003-01-01

A method, simulation, and apparatus are provided that are highly suitable for treatment of benign prostatic hyperplasia (BPH). A catheter is disclosed that includes a small diameter disk loaded monopole antenna surrounded by fusion material having a high heat of fusion and a melting point preferably at or near body temperature. Microwaves from the antenna heat prostatic tissue to promote necrosing of the prostatic tissue that relieves the pressure of the prostatic tissue against the urethra as the body reabsorbs the necrosed or dead tissue. The fusion material keeps the urethra cool by means of the heat of fusion of the fusion material. This prevents damage to the urethra while the prostatic tissue is necrosed. A computer simulation is provided that can be used to predict the resulting temperature profile produced in the prostatic tissue. By changing the various control features of the catheter and method of applying microwave energy a temperature profile can be predicted and produced that is similar to the temperature profile desired for the particular patient.

Method for Selective Thermal Ablation

NASA Technical Reports Server (NTRS)

Arndt, G. Dickey (Inventor); Carl, James (Inventor); Ngo, Phong (Inventor); Raffoul, George W. (Inventor)

2003-01-01

A method, simulation, and apparatus are provided that are highly suitable for treatment of benign prostatic hyperplasia (BPH). A catheter is disclosed that includes a small diameter disk loaded monopole antenna surrounded by fusion material having a high heat of fusion and a melting point preferably at or near body temperature. Microwaves from the antenna heat prostatic tissue to promote necrosing of the prostatic tissue that relieves the pressure of the prostatic tissue against the urethra as the body reabsorbs the necrosed or dead tissue. The fusion material keeps the urethra cool by means of the heat of fusion of the fusion material. This prevents damage to the urethra while the prostatic tissue is necrosed. A computer simulation is provided that can be used to predict the resulting temperature profile produced in the prostatic tissue. By changing the various control features of the catheter and method of applying microwave energy a temperature profile can be predicted and produced that is similar to the temperature profile desired for the particular patient.

Transcatheter Microwave Antenna

NASA Technical Reports Server (NTRS)

Arndt, Dickey G. (Inventor); Carl, James R. (Inventor); Ngo, Phong (Inventor); Raffoul, George W. (Inventor)

2001-01-01

A method, simulation, and apparatus are provided that are highly suitable for treatment of benign prostatic hyperplasia (BPH). A catheter is disclosed that includes a small diameter disk loaded monopole antenna surrounded by fusion material having a high heat of fusion and a melting point preferably at or near body temperature. Microwaves from the antenna heat prostatic tissue to promote necrosing of the prostatic tissue that relieves the pressure of the prostatic tissue against the urethra as the body reabsorbs the necrosed or dead tissue. The fusion material keeps the urethra cool by means of the heat of fusion of the fusion material. This prevents damage to the urethra while the prostatic tissue is necrosed. A computer simulation is provided that can be used to predict the resulting temperature profile produced in the prostatic tissue. By changing the various control features of the catheter and method of applying microwave energy a temperature profile can be predicted and produced that is similar to the temperature profile desired for the particular patient.

Prostate Mechanical Imaging: A New Method For Prostate Assessment

PubMed Central

Weiss, Robert E; Egorov, Vladimir; Ayrapetyan, Suren; Sarvazyan, Noune; Sarvazyan, Armen

2008-01-01

Objectives To evaluate the ability of Prostate Mechanical Imaging (PMI) technology to provide an objective and reproducible image and to assess the prostate nodularity. Methods The PMI device developed by Artann Laboratories was evaluated in a pilot clinical study. For the 168 patients (ages 44 to 94) presented to an urologist for prostate evaluation, PMI-produced images and assessment of prostate size, shape, consistency/hardness, mobility, nodularity, and was compared with digital rectal examination (DRE) findings. The PMI and DRE results were further tested for correlation against a transrectal ultrasound of the prostate (TRUS) guided biopsy for a sub-group of 21 patients with an elevated PSA level. Results In 84% of the cases the PMI device was able to reconstruct 3-D and 2-D cross-sectional images of the prostate. The PMI System and DRE pre-tests were able to determine malignant nodules in 10 and 6 patients, respectively, of the 13 patients with biopsy-confirmed malignant inclusions. The PMI System findings were consistent with all 8 biopsy negative cases, while the DRE had 1 abnormal reading for this group. The correlation between PMI and DRE detection of palpable nodularity was 81%, as indicated by the area under the receiver operating characteristic (ROC) curve. Estimates of the prostate size provided by PMI and DRE were found to be statistically significantly correlated. Conclusions The PMI has the potential to enable a physician to obtain, examine and store a three dimensional image of the prostate based on mechanical and geometrical characteristics of the gland and its internal structures. PMID:18342178

SU-G-TeP1-01: A Simulation Study to Investigate Maximum Allowable Deformations of Implant Geometry Before Plan Objectives Are Violated in Prostate HDR Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Babier, A; Joshi, C; Cancer Center of Southeastern Ontario, Kingston General Hospital, Kingston, Ontario

Purpose: In prostate HDR brachytherapy dose distributions are highly sensitive to changes in prostate volume and catheter displacements. We investigate the maximum deformations in implant geometry before planning objectives are violated. Methods: A typical prostate Ir-192 HDR brachytherapy reference plan was calculated on the Oncentra planning system, which used CT images from a tissue equivalent prostate phantom (CIRS Model 053S) embedded inside a pelvis wax phantom. The prostate was deformed and catheters were displaced in simulations using a code written in MATLAB. For each deformation dose distributions were calculated, based on TG43 methods, using the MATLAB code. The calculations weremore » validated through comparison with Oncentra calculations for the reference plan, and agreed within 0.12%SD and 0.3%SD for dose and volume, respectively. Isotropic prostate volume deformations of up to +34% to −27% relative to its original volume, and longitudinal catheter displacements of 7.5 mm in superior and inferior directions were simulated. Planning objectives were based on American Brachytherapy Society guidelines for prostate and urethra volumes. A plan violated the planning objectives when less than 90% of the prostate volume received the prescribed dose or higher (V{sub 100}), or the urethral volume receiving 125% of prescribed dose or higher was more than 1 cc (U{sub 125}). Lastly, the dose homogeneity index (DHI=1-V{sub 150}/V{sub 100}) was evaluated; a plan was considered sub-optimal when the DHI fell below 0.62. Results and Conclusion: Planning objectives were violated when the prostate expanded by 10.7±0.5% or contracted by 11.0±0.2%; objectives were also violated when catheters were displaced by 4.15±0.15 mm and 3.70±0.15 mm in the superior and inferior directions, respectively. The DHI changes did not affect the plan optimality, except in the case of prostate compression. In general, catheter displacements have a significantly larger impact on plan optimality than prostate volume changes.« less

Comparison of semen parameters in samples collected by masturbation at a clinic and at home.

PubMed

Elzanaty, Saad; Malm, Johan

2008-06-01

To investigate differences in semen quality between samples collected by masturbation at a clinic and at home. Cross-sectional study. Fertility center. Three hundred seventy-nine men assessed for infertility. None. Semen was analyzed according to World Health Organization guidelines. Seminal markers of epididymal (neutral alpha-glucosidase), prostatic (prostate-specific antigen and zinc), and seminal vesicle (fructose) function were measured. Two patient groups were defined according to sample collection location: at a clinic (n = 273) or at home (n = 106). Compared with clinic-collected semen, home-collected samples had statistically significantly higher values for sperm concentration, total sperm count, rapid progressive motility, and total count of progressive motility. Semen volume, proportion of normal sperm morphology, neutral alpha-glucosidase, prostate-specific antigen, zinc, and fructose did not differ significantly between groups. An abnormal sperm concentration (<20 x 10(6)/mL) was seen in statistically significantly fewer of the samples obtained at home (19/106, 18%) than at the clinic (81/273, 30%), and the same applied to proportions of samples with abnormal (< 25%) rapid progressive motility (68/106 [64%] and 205/273 [75%], respectively). The present results demonstrate superior semen quality in samples collected by masturbation at home compared with at a clinic. This should be taken into consideration in infertility investigations.

The eternal enigma in prostatic biopsy access route.

PubMed

Fabiani, Andrea; Principi, Emanuele; Filosa, Alessandra; Servi, Lucilla

2017-10-03

Dear Editors,We read with interest the article by Di Franco and co-workers (1). The introduction of prostatic magnetic resonance and the relative fusion-biopsy have not yet allowed the expected improvements in prostate biopsy. To our knowledge, there are no works that demonstrate the superiority of fusion techniques on the remaining ultrasound guided prostate biopsies that are still the widely used in the diagnosis of prostate cancer. Furthemore, these technologies are expensive exams and they are not yet available in all centers, especially in those minors. We work at a "minor" center and we always keep in mind that the goal of  prostatic biopsy is the diagnosis and the staging of prostatic neoplasms.. However, it remains uncertain which of the two techniques, transperineal (TP) or transrectal (TR), is superior in terms of detection rate during first biopsy setting. Several studies have compared the prostate cancer detection rate but TR and TP access route in prostatic gland sampling seems to be equivalent in terms of efficiency and complications, as reported by Shen PF et al. (2), despite several methodological limitations recognized in their work. The results reported by Di Franco CA et al. represent the real life experience of most urologists that perform the PB based on their own training experience and available technical devices. From an historical viewpoint, the TP route has been the first one to be used to reach the prostate, both for diagnostic and therapeutic purposes. To date, because it seems to be more invasive and difficult, the TP route is less used worldwide than the TR one (2). Theoretically, the TP approach should detect more prostate cancer than the TR way  because the cores of the TP approach are directed longitudinally to the peripheral zone and the anterior part of the prostate (4). The results reported by Di Franco et al. seems to confirm these considerations. However, our real life experience differ from the conclusions reached in their work. We recently conducted a prospective evaluation of 352 patients who underwent their first prostate biopsy because of a suspicious of prostate cancer (elevated prostate specific antigen (PSA) and/or abnormal digital rectal examination and/or abnormal findings on transrectal prostatic ultrasound). Patients was randomized as following. A total of 187 patients (Group A) underwent a prostatic biopsy with a transperineal approach in a lithotomic position,  using a biplane probe (8818 BK Medical, Denmark) and a fan technique with a single perineal median access (5). The remnants 165 patients (Group B) underwent a transrectal ultrasound guided prostate biopsy in a left lateral position, using a end fire probe configuration (8818 BK Medical, Denmark) and a sagittal technique. The bioptic prostatic mapping was performed with a 12-core scheme sec. Gore (3) by a single experienced operator and the histopathologic evaluation was performed by a single dedicated uro-pathologist. Statistical evaluations were made with a T Student test  (p<0,005). Group A and Group B was similar in term of mean patient age (67,9 years and 67 years respectively), mean total PSA (12,1 ng/ml vs 12 ng/ml) and digital rectal examination positivity (22% vs 29%).  The global cancer detection rate was 33,69% (63/187) in the transperineal prostate biopsy group and 48,48 % (80/165) in the transrectal approach (p=0.0047).  No significant statistical differences were found in the complications rates between the two groups. Statistical evaluation of site of tumor localization reveal only a trend to statistical significance in apical site tumors diagnosed with the TR approach versus the TP technique. The TR approach had a better diagnostic accuracy than TP technique in case of PSA<4 ng/ml, intermediate prostate volume (30 and 50 ml), normal digital rectal examination without any relationship with the patient age. In our experience, two aspect may explain the difference between the two group in term of global detection rate. First, we usually perform transrectal biopsy with a sagittal technique that simulates the transperineal way of needle incidence with the prostatic gland. The lateral and anterior gland portions may be sampled more accurately. Second, our transperineal approach consists in a single perineal median access that can make more difficult the gland sampling between the two lobes. However, there was no significant difference in core positivity rate at the peripheral zone, medium gland, apex or any other site such as reported in many randomized clinical trials (2). Unlike the conclusions reported by Di Franco et al., in our experience we found a statistically significant difference between the TR and TP approach, at the first biopsy setting, in term of global cancer detection rate. No differences were found in terms of complications. Moreover, our data suggest that TR approach had a better diagnostic accuracy than TP technique in case of  PSA<4 ng/ml, prostate volume 30-50 ml, normal digital rectal examination without any relationship with the patient age. The further step of the statistical evaluation of our data will be the definition of the possibility that the TR biopsy determine a better staging of prostate cancer than TP approach as first procedure.    REFERENCES 1)      Di Franco CA, Jallous H., Porru D. et al. A retrospective comparison between transrectal and transperineal prostate biopsy in the detection of prostate cancer Arch Ital Urol Androl 2017; 89(1), 55-92)      Shen FP, Zhu YC, Wei WR et al. The results of transperineal vs transrectal prostate biopsy: a systematic review and meta-analysis. Asian Journal of Androl 2012; 14: 310-15.3)      Gore JL., Shariat SF, Miles BJ., et al. Optimal combinations of systematic sextant and laterally directed biopsies for the detection of prostate cancer. J Urol 2001; 165: 1554-59.  4)      Abdollah F., Novara G., Briganti A. et al. Trasrectal versus transperineal saturation re biopsy of the prostate: is there a difference in cancer detection rate? Urology 2011; 77:9215)      Novella G, Ficarra V, Galfano A, et al. Pain assessment after original transperineal prostate biopsy using a coaxial needle. Urology. 2003; 62 : 689-92.

A retrospective study: correlation of histologic inflammation in biopsy specimens of Chinese men undergoing surgery for benign prostatic hyperplasia with serum prostate-specific antigen.

PubMed

Song, Lingmin; Zhu, Yuchun; Han, Ping; Chen, Ni; Lin, Dao; Lai, Jianyu; Wei, Qiang

2011-03-01

To reveal the correlation between benign prostatic hyperplasia (BPH) histologic inflammation and serum prostate-specific antigen (sPSA) concentrations, and the possible mechanism. Patients underwent surgery at the Urology Department of West China Hospital of Sichuan University were retrospectively studied. Preoperative sPSA and transrectal ultrasonography were measured. According to the histopathological classification system for chronic prostatic inflammation proposed by the Chronic Prostatitis Collaborative Research Network (CPCRN) and the International Prostatitis Collaborative Network (IPCN), we classified the histologic sections of prostatic biopsy into glandular, periglandular, and stromal inflammation by the anatomical location of inflammatory infiltration. The glandular inflammation was graded according to the inflammatory aggressiveness. The periglandular and stromal inflammation were graded according to the inflammatory density. The correlation between histologic inflammation and sPSA was studied by a multiple regression model in conjunction with age and total prostatic volume. A total of 454 patients with exclusively BPH were analyzed. The periglandular inflammatory infiltration was the most common pattern (95.6%). Single regression analysis revealed that total prostatic volume, the aggressiveness of glandular inflammation, and the intensity of periglandular and stromal inflammation were correlated with sPSA. However, the multiple regression analysis revealed that only the total prostatic volume and the aggressiveness of glandular inflammation were correlated significantly with sPSA (R = .389, 0.289; P = .000). The aggressiveness of glandular inflammatory infiltration in BPH is a significant contributor to elevated sPSA levels. The theory of leakage may be the most reasonable mechanism to reveal the correlation morphologically. We should take inflammation into consideration when interpreting the abnormal elevating of sPSA levels. Copyright © 2011 Elsevier Inc. All rights reserved.

Association of serum prostate-specific antigen levels with the results of the prostate needle biopsy.

PubMed

Janbaziroudsari, Hamid; Mirzaei, Arezoo; Maleki, Nasrollah

2016-09-01

To investigate the relationship of serum prostate-specific antigen (PSA) levels with outcomes of prostate needle biopsy in men 50 or more years old. We measured serum PSA levels in 1472 healthy men 50 or more years old. Men who had serum PSA values 4.0ng/mL or higher underwent digital rectal examination. If there were either an elevated PSA level (≥4ng/mL) or abnormal digital rectal examination, a transrectal ultrasound-guided prostate biopsy was performed. The mean serum total PSA level was 13.73±11.44ng/mL, and the mean serum free PSA level was 4.99±0.97ng/mL. Of the 260 men who had serum total PSA levels of≥4ng/mL, 139 underwent biopsy. Of these 139 men, 45 (32.4%) had prostate cancer. Benign prostatic hyperplasia with or without prostatitis was diagnosed in 94 patients (67.6%). There was no significant correlation between age and histologic results of prostate needle biopsy (P-value=0.469). The serum free PSA showed no significant correlation with histologic results of prostate needle biopsy, whereas the serum total PSA level had a significant correlation in patients with adenocarcinoma compared with other diagnosis. The overall frequency of detection of prostate adenocarcinoma was 32.4%. This study revealed that no level of PSA was associated with a 100% positive predictive value and negative biopsy can occur virtually at any PSA level. There is a need to create awareness among the general population and health professionals for an early diagnosis of this common form of cancer. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Effect of Pulsed Electromagnetic Field Therapy on Prostate Volume and Vascularity in the Treatment of Benign Prostatic Hyperplasia: A Pilot Study in a Canine Model

PubMed Central

Leoci, Raffaella; Aiudi, Giulio; Silvestre, Fabio; Lissner, Elaine; Lacalandra, Giovanni Michele

2014-01-01

BACKGROUND Benign prostatic hyperplasia (BPH) is a result of urogenital aging. Recent studies suggest that an age-related impairment of the blood supply to the lower urinary tract plays a role in the development of BPH and thus may be a contributing factor in the pathogenesis of BPH. The canine prostate is a model for understanding abnormal growth of the human prostate gland. We studied the efficacy of pulsed electromagnetic field therapy (PEMF) in dogs to modify prostate blood flow and evaluated its effect on BPH. METHODS PEMF (5 min, twice a day for 3 weeks) was performed on 20 dogs affected by BPH. Prostatic volume, Doppler assessment by ultrasonography, libido, semen quality, testosterone levels, and seminal plasma volume, composition and pH were evaluated before and after treatment. RESULTS The 3 weeks of PEMF produced a significant reduction in prostatic volume (average 57%) without any interference with semen quality, testosterone levels or libido. Doppler parameters showed a reduction of peripheral resistances and a progressive reduction throughout the trial of the systolic peak velocity, end-diastolic velocity, mean velocity, mean, and peak gradient of the blood flow in the dorsal branch of the prostatic artery. The pulsatility index and the resistance index did not vary significantly over time. CONCLUSIONS The efficacy of PEMF on BPH in dogs, with no side effects, suggests the suitability of this treatment in humans and supports the hypothesis that impairment of blood supply to the lower urinary tract may be a causative factor in the development of BPH. Prostate 74:1132–1141, 2014. © 2014 The Authors. The Prostate published by Wiley Periodicals, Inc. PMID:24913937

A novel SPECT camera for molecular imaging of the prostate

NASA Astrophysics Data System (ADS)

Cebula, Alan; Gilland, David; Su, Li-Ming; Wagenaar, Douglas; Bahadori, Amir

2011-10-01

The objective of this work is to develop an improved SPECT camera for dedicated prostate imaging. Complementing the recent advancements in agents for molecular prostate imaging, this device has the potential to assist in distinguishing benign from aggressive cancers, to improve site-specific localization of cancer, to improve accuracy of needle-guided prostate biopsy of cancer sites, and to aid in focal therapy procedures such as cryotherapy and radiation. Theoretical calculations show that the spatial resolution/detection sensitivity of the proposed SPECT camera can rival or exceed 3D PET and further signal-to-noise advantage is attained with the better energy resolution of the CZT modules. Based on photon transport simulation studies, the system has a reconstructed spatial resolution of 4.8 mm with a sensitivity of 0.0001. Reconstruction of a simulated prostate distribution demonstrates the focal imaging capability of the system.

Computation of restoration of ligand response in the random kinetics of a prostate cancer cell signaling pathway.

PubMed

Dana, Saswati; Nakakuki, Takashi; Hatakeyama, Mariko; Kimura, Shuhei; Raha, Soumyendu

2011-01-01

Mutation and/or dysfunction of signaling proteins in the mitogen activated protein kinase (MAPK) signal transduction pathway are frequently observed in various kinds of human cancer. Consistent with this fact, in the present study, we experimentally observe that the epidermal growth factor (EGF) induced activation profile of MAP kinase signaling is not straightforward dose-dependent in the PC3 prostate cancer cells. To find out what parameters and reactions in the pathway are involved in this departure from the normal dose-dependency, a model-based pathway analysis is performed. The pathway is mathematically modeled with 28 rate equations yielding those many ordinary differential equations (ODE) with kinetic rate constants that have been reported to take random values in the existing literature. This has led to us treating the ODE model of the pathways kinetics as a random differential equations (RDE) system in which the parameters are random variables. We show that our RDE model captures the uncertainty in the kinetic rate constants as seen in the behavior of the experimental data and more importantly, upon simulation, exhibits the abnormal EGF dose-dependency of the activation profile of MAP kinase signaling in PC3 prostate cancer cells. The most likely set of values of the kinetic rate constants obtained from fitting the RDE model into the experimental data is then used in a direct transcription based dynamic optimization method for computing the changes needed in these kinetic rate constant values for the restoration of the normal EGF dose response. The last computation identifies the parameters, i.e., the kinetic rate constants in the RDE model, that are the most sensitive to the change in the EGF dose response behavior in the PC3 prostate cancer cells. The reactions in which these most sensitive parameters participate emerge as candidate drug targets on the signaling pathway. 2011 Elsevier Ireland Ltd. All rights reserved.

Karyometry detects subvisual differences in chromatin organization state between cribriform and flat high-grade prostatic intraepithelial neoplasia.

PubMed

Montironi, Rodolfo; Thompson, Deborah; Scarpelli, Marina; Mazzucchelli, Roberta; Peketi, Prasanthi; Hamilton, Peter W; Bostwick, David G; Bartels, Peter H

2004-08-01

This digital texture analysis-based study evaluates the chromatin organization state in flat and cribriform high-grade prostatic intraepithelial neoplasia (PIN), in the adjacent normal looking secretory epithelium and in the co-occurring adenocarcinoma. Digital texture analysis (karyometry) was carried out on hematoxylin and eosin-stained sections from 24 radical prostatectomy specimens with high-grade PIN (12 with flat and 12 with cribriform architectural pattern, respectively) and cancer. Quantification was also conducted on the normal looking secretory epithelium. Discriminant analysis and the nonsupervised learning algorithm P-index were used to identify suitable subsets of features useful for the discrimination and classification of pathological groups and to explore multivariate data structure in the pathological subgroups. The average nuclear abnormality increases monotonically from the histologically normal appearing secretory epithelium to high-grade PIN and to adenocarcinoma. The nuclei from the so-called perimeter compartment of the flat high-grade PIN lesions show a higher nuclear abnormality compared to the nuclei of the cribriform high-grade PINs. Discriminant analysis shows that flat and cribriform high-grade PINs fall into two populations. Processing by the nonsupervised learning algorithm P-index revealed the existence of three well-defined, distinct subpopulations of nuclei of different chromatin phenotype. In the flat high-grade PIN lesions the proportions of nuclei in the three subpopulations are 16.5% (low abnormality), 25.0% (mid abnormality) and 58.5% (high abnormality), respectively. In the cribriform high-grade PIN lesions, 100% of the nuclei are in the mid-abnormality subpopulation. These differences are also discernible in the co-occurring adenocarcinoma and the histologically normal appearing secretory epithelium. To conclude, karyometry and statistical analysis detect the existence of distinct cell subpopulations of different chromatin packaging and phenotype, with the nuclei from the flat high-grade PIN lesions, adjacent normal looking epithelium and co-occurring adenocarcinoma expressing a greater nuclear abnormality than in the specimens with cribriform high-grade PIN.

Comparison of Dosimetric and Biologic Effective Dose Parameters for Prostate and Urethra Using {sup 131}Cs and {sup 125}I for Prostate Permanent Implant Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sahgal, Arjun; Department of Radiation Oncology, Odette Cancer Centre at Sunnybrook Hospital, University of Toronto, Toronto, ON; Jabbari, Siavash

2008-09-01

Purpose: To compare the urethral and prostate absolute and biologic effective doses (BEDs) for {sup 131}Cs and {sup 125}I prostate permanent implant brachytherapy (PPI). Methods and Materials: Eight previously implanted manually planned {sup 125}I PPI patients were replanned manually with {sup 131}Cs, and re-planned using Inverse Planning Simulated Annealing. {sup 131}Cs activity and the prescribed dose (115 Gy) were determined from that recommended by IsoRay. The BED was calculated for the prostate and urethra using an {alpha}/{beta} ratio of 2 and was also calculated for the prostate using an {alpha}/{beta} ratio of 6 and a urethral {alpha}/{beta} ratio of 2.more » The primary endpoints of this study were the prostate D{sub 90} BED (pD{sub 90}BED) and urethral D{sub 30} BED normalized to the maximal potential prostate D{sub 90} BED (nuD{sub 30}BED). Results: The manual plan comparison ({alpha}/{beta} = 2) yielded no significant difference in the prostate D{sub 90} BED (median, 192 Gy{sub 2} for both isotopes). No significant difference was observed for the nuD{sub 30}BED (median, 199 Gy{sub 2} and 202 Gy{sub 2} for {sup 125}I and {sup 131}Cs, respectively). For the inverse planning simulated annealing plan comparisons ({alpha}/{beta} 2), the prostate D{sub 90} BED was significantly lower with {sup 131}Cs than with {sup 125}I (median, 177 Gy{sub 2} vs. 187 Gy{sub 2}, respectively; p = 0.01). However, the nuD{sub 30}BED was significantly greater with {sup 131}Cs than with {sup 125}I (median, 192 Gy{sub 2} vs. 189 Gy{sub 2}, respectively; p = 0.01). Both the manual and the inverse planning simulated annealing plans resulted in a significantly lower prostate D{sub 90} BED (p = 0.01) and significantly greater nuD{sub 30}BED for {sup 131}Cs (p = 0.01), compared with {sup 125}I, when the prostate {alpha}/{beta} ratio was 6 and the urethral {alpha}/{beta} ratio was 2. Conclusion: This report highlights the controversy in comparing the dose to both the prostate and the organs at risk with different radionuclides.« less

Racial differences in clinically localized prostate cancers of black and white men.

PubMed

deVere White, R W; Deitch, A D; Jackson, A G; Gandour-Edwards, R; Marshalleck, J; Soares, S E; Toscano, S N; Lunetta, J M; Stewart, S L

1998-06-01

Tumor grade, deoxyribonucleic acid (DNA) ploidy, proliferation, p53 and bcl-2 expression were examined in clinically localized prostate cancers of black and white American men to learn whether these features showed racial differences. A total of 117 prostate cancers (43 black and 74 white patients) obtained at radical prostatectomy for clinically localized disease were assigned Gleason scores by a single pathologist. Enzymatically dissociated nuclei from archival prostate cancers were examined by DNA flow cytometry using propidium iodide staining and the multicycle program to remove debris and sliced nuclei and to perform cell cycle analysis. For immunostaining after microwave antigen retrieval we used a DO-1/DO-7 monoclonal antibody cocktail for p53 and the clone 124 antibody for bcl-2. Significantly more black than white men had Gleason score 7 tumors. The DNA ploidy distribution of Gleason 6 or less tumors was similar for both races. As anticipated, the ploidy distribution of higher grade prostate cancer in white men was more abnormal but, unexpectedly, this was not found for higher grade prostate cancer in black men. No significant racial differences were found in S phase fractions, p53 or bcl-2 immunopositivity. However, for prostate cancer in black men there was a significant association between bcl-2 immunopositivity and higher S-phase fractions. The aggressive prostate cancers of black men may be characterized by the 2 features of high proliferation and a block to programmed cell death.

Prostate-specific antigen density values among patients with symptomatic prostatic enlargement in Nigeria.

PubMed

Udeh, Emeka I; Nnabugwu, Ikenna I; Ozoemena, Francis O; Ugwumba, Fred O; Aderibigbe, Adesina S O; Ohayi, Samuel R; Echetabu, Kevin N

2016-06-29

This study aims to estimate the prostate-specific antigen density (PSAD) cutoff level for detecting prostate cancer (CAP) in Nigerian men with "grey zone PSA" (4-10 ng/ml) and normal digital rectal examination findings. We addressed this research question: Is the international PSAD cutoff of 0.15 ideal for detecting CAP in our symptomatic patients with "grey zone PSA?" To estimate the prostate-specific antigen density (PSAD) cutoff level for detecting CAP in Nigerian men with "grey zone PSA" (4-10 ng/ml) and normal digital rectal examination findings. Prospective. A tertiary medical center in Enugu, Nigeria. Two hundred and fifty-four men with either benign prostatic hyperplasia (BPH) or CAP were recruited. Patients with PSA above 4 ng/ml or abnormal digital rectal examination or hypoechoic lesion in the prostate were biopsied. PSAD and histology report of BPH or CAP. Ninety-seven patients had CAP while 157 had benign prostatic hyperplasia (BPH). Seventy-two patients had their serum PSA value within the range of 4.0 and 10 ng/ml. PSAD cutoff level to detect CAP was 0.04 (sensitivity 95.88 %; specificity 28.7 %). The PSAD cutoff level generated for Nigerian men in this study is 0.04 which is relatively different from international consensus. This PSAD cutoff level has a positive correlation with histology and could detect patients with CAP who have "grey zone PSA."

The change in serum Thiol/Disulphide homeostasis after transrectal ultrasound guided prostate biopsy

PubMed Central

Tokgöz, Hüsnü; Taş, Selim; Giray, Özlem; Yalçınkaya, Soner; Tokgöz, Özlem; Koca, Cemile; Savaş, Murat; Erel, Özcan

2017-01-01

ABSTRACT Objectives The aim of this prospective clinical study was to investigate variations in a novel oxidative stress marker (thiol/disulphide homeostasis) in men who underwent transrectal ultrasound guided prostate biopsy (TRUSB). Materials and Methods A total of 22 men undergoing TRUSB of the prostate were enrolled in the study. Patients with abnormal digital rectal examination and/or total prostate specific antigen (PSA) over 4ng/mL underwent TRUSB with 12 cores. Serum samples were obtained before and just after the procedure to evaluate the possible changes in thiol/disulphide homeostasis. Mean age, total PSA and free PSA, prostate volume and histopathological data were also recorded. Results Mean age of the study population was 65.05±8.89 years. Significant decreases in native and total thiol levels were documented after the biopsy procedure. However, serum disulphide levels and disulphide/native thiol, disulphide/total thiol and native/total thiol ratios did not significantly change after TRUSB. No correlation was observed between oxidative parameters and total PSA and free PSA levels, prostate volume and histopathology of the prostate. However, mean patient age was significantly correlated with mean native and total thiol levels. Conclusion Significant decreases in serum native and total thiol levels related to the prostate biopsy procedure suggest that TRUSB causes acute oxidative stress in the human body. Since our trial is the first in the current literature to investigate these oxidative stress markers in urology practice, additional studies are warranted. PMID:28128906

The change in serum Thiol/Disulphide homeostasis after transrectal ultrasound guided prostate biopsy.

PubMed

Tokgöz, Hüsnü; Taş, Selim; Giray, Özlem; Yalçınkaya, Soner; Tokgöz, Özlem; Koca, Cemile; Savaş, Murat; Erel, Özcan

2017-01-01

The aim of this prospective clinical study was to investigate variations in a novel oxidative stress marker (thiol/disulphide homeostasis) in men who underwent transrectal ultrasound guided prostate biopsy (TRUSB). A total of 22 men undergoing TRUSB of the prostate were enrolled in the study. Patients with abnormal digital rectal examination and/or total prostate specific antigen (PSA) over 4ng/mL underwent TRUSB with 12 cores. Serum samples were obtained before and just after the procedure to evaluate the possible changes in thiol/disulphide homeostasis. Mean age, total PSA and free PSA, prostate volume and histopathological data were also recorded. Mean age of the study population was 65.05±8.89 years. Significant decreases in native and total thiol levels were documented after the biopsy procedure. However, serum disulphide levels and disulphide/native thiol, disulphide/total thiol and native / total thiol ratios did not significantly change after TRUSB. No correlation was observed between oxidative parameters and total PSA and free PSA levels, prostate volume and histopathology of the prostate. However, mean patient age was significantly correlated with mean native and total thiol levels. Significant decreases in serum native and total thiol levels related to the prostate biopsy procedure suggest that TRUSB causes acute oxidative stress in the human body. Since our trial is the first in the current literature to investigate these oxidative stress markers in urology practice, additional studies are warranted. Copyright® by the International Brazilian Journal of Urology.

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

PubMed

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.

Metabolic syndrome, endocrine disruptors and prostate cancer associations: biochemical and pathophysiological evidences

PubMed Central

Quagliariello, Vincenzo; Rossetti, Sabrina; Cavaliere, Carla; Di Palo, Rossella; Lamantia, Elvira; Castaldo, Luigi; Nocerino, Flavia; Ametrano, Gianluca; Cappuccio, Francesca; Malzone, Gabriella; Montanari, Micaela; Vanacore, Daniela; Romano, Francesco Jacopo; Piscitelli, Raffaele; Iovane, Gelsomina; Pepe, Maria Filomena; Berretta, Massimiliano; D'Aniello, Carmine; Perdonà, Sisto; Muto, Paolo; Botti, Gerardo; Ciliberto, Gennaro; Veneziani, Bianca Maria; De Falco, Francesco; Maiolino, Piera; Caraglia, Michele; Montella, Maurizio; Iaffaioli, Rosario Vincenzo; Facchini, Gaetano

2017-01-01

This review summarizes the main pathophysiological basis of the relationship between metabolic syndrome, endocrine disruptor exposure and prostate cancer that is the most common cancer among men in industrialized countries. Metabolic syndrome is a cluster of metabolic and hormonal factors having a central role in the initiation and recurrence of many western chronic diseases including hormonal-related cancers and it is considered as the worlds leading health problem in the coming years. Many biological factors correlate metabolic syndrome to prostate cancer and this review is aimed to focus, principally, on growth factors, cytokines, adipokines, central obesity, endocrine abnormalities and exposure to specific endocrine disruptors, a cluster of chemicals, to which we are daily exposed, with a hormone-like structure influencing oncogenes, tumor suppressors and proteins with a key role in metabolism, cell survival and chemo-resistance of prostate cancer cells. Finally, this review will analyze, from a molecular point of view, how specific foods could reduce the relative risk of incidence and recurrence of prostate cancer or inhibit the biological effects of endocrine disruptors on prostate cancer cells. On the basis of these considerations, prostate cancer remains a great health problem in terms of incidence and prevalence and interventional studies based on the treatment of metabolic syndrome in cancer patients, minimizing exposure to endocrine disruptors, could be a key point in the overall management of this disease. PMID:28389628

Metabolic syndrome, endocrine disruptors and prostate cancer associations: biochemical and pathophysiological evidences.

PubMed

Quagliariello, Vincenzo; Rossetti, Sabrina; Cavaliere, Carla; Di Palo, Rossella; Lamantia, Elvira; Castaldo, Luigi; Nocerino, Flavia; Ametrano, Gianluca; Cappuccio, Francesca; Malzone, Gabriella; Montanari, Micaela; Vanacore, Daniela; Romano, Francesco Jacopo; Piscitelli, Raffaele; Iovane, Gelsomina; Pepe, Maria Filomena; Berretta, Massimiliano; D'Aniello, Carmine; Perdonà, Sisto; Muto, Paolo; Botti, Gerardo; Ciliberto, Gennaro; Veneziani, Bianca Maria; De Falco, Francesco; Maiolino, Piera; Caraglia, Michele; Montella, Maurizio; Iaffaioli, Rosario Vincenzo; Facchini, Gaetano

2017-05-02

This review summarizes the main pathophysiological basis of the relationship between metabolic syndrome, endocrine disruptor exposure and prostate cancer that is the most common cancer among men in industrialized countries. Metabolic syndrome is a cluster of metabolic and hormonal factors having a central role in the initiation and recurrence of many western chronic diseases including hormonal-related cancers and it is considered as the world's leading health problem in the coming years. Many biological factors correlate metabolic syndrome to prostate cancer and this review is aimed to focus, principally, on growth factors, cytokines, adipokines, central obesity, endocrine abnormalities and exposure to specific endocrine disruptors, a cluster of chemicals, to which we are daily exposed, with a hormone-like structure influencing oncogenes, tumor suppressors and proteins with a key role in metabolism, cell survival and chemo-resistance of prostate cancer cells. Finally, this review will analyze, from a molecular point of view, how specific foods could reduce the relative risk of incidence and recurrence of prostate cancer or inhibit the biological effects of endocrine disruptors on prostate cancer cells. On the basis of these considerations, prostate cancer remains a great health problem in terms of incidence and prevalence and interventional studies based on the treatment of metabolic syndrome in cancer patients, minimizing exposure to endocrine disruptors, could be a key point in the overall management of this disease.

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

PubMed

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.

Early diagnostic role of PSA combined miR-155 detection in prostate cancer.

PubMed

Guo, T; Wang, X-X; Fu, H; Tang, Y-C; Meng, B-Q; Chen, C-H

2018-03-01

As a kind of malignant tumor in the male genitourinary system, prostate cancer exhibits significantly increased occurrence. Prostate-specific antigen (PSA) expression can be seen in the prostate cancer, prostatitis, and other diseases, therefore, lack of diagnostic specificity. The miR-155 expression is abnormally increased in the tumors. Therefore, this study aims to explore the clinical significance of PSA combined miR-155 detection in the early diagnosis of prostate cancer. A total of 86 patients diagnosed with prostate cancer were enrolled in this study. PSA and miR-155 gene expression in tumor tissue were detected by using Real-time PCR. The serum levels of PSA were measured by using enzyme-linked immunosorbent assay (ELISA). The correlation of PSA and miR-155 expression with age, body mass index (BMI), tumor volume, tumor-node-metastasis (TNM) stage, lymph node metastasis (LNM), and other clinicopathological features were analyzed, respectively. Serum PSA expression and PSA gene in tumor tissue were significantly higher compared to that in adjacent tissues (p<0.05). PSA gene and protein increased significantly with the clinical stage of TNM and decreased following the increase of grade (p<0.05). The miR-155 level was significantly elevated in the tumor tissue compared with para-carcinoma tissue (p<0.05). PSA and miR-155 expressions were positively correlated with TNM stage, tumor volume, and LNM, and negatively correlated with grade (p<0.05). PSA and miR-155 were closely related to the clinicopathological features of prostate cancer. Combined detection is helpful for the early diagnosis of prostate cancer.

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

PubMed

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 <20 ng/ml and underwent initial transrectal ultrasound-guided prostate biopsy with at least 10 cores sampling for suspicious exam and/or elevated PSA. Covariates were collected for the nomogram and included age, ethnicity, family history (FH) of 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 < 0.001). Despite the differences in 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.

Cellular and molecular effects of developmental exposure to diethylstilbestrol: implications for other environmental estrogens.

PubMed Central

Newbold, R

1995-01-01

Concerns have been raised regarding the role of environmental and dietary estrogens as possible contributors to an increased incidence of various abnormalities in estrogen-target tissues of both sexes. These abnormalities include breast cancer, endometriosis, fibroids, and uterine adenocarcinoma in females, as well as alterations in sex differentiation, decreased sperm concentrations, benign prostatic hyperplasia, prostatic cancer, testicular cancer, and reproductive problems in males. Whether these concerns are valid remains to be determined; however, studies with the potent synthetic estrogen diethylstilbestrol (DES) suggest that exogenous estrogen exposure during critical stages of development can result in permanent cellular and molecular alterations in the exposed organism. These alterations manifest themselves in the female and male as structural, functional, or long-term pathological changes including neoplasia. Although DES has potent estrogenic activity, it may be used as a model compound to study the effects of weaker environmental estrogens, many of which may fit into the category of endocrine disruptors. PMID:8593881

Establishing High-Quality Prostate Brachytherapy Using a Phantom Simulator Training Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thaker, Nikhil G.; Kudchadker, Rajat J.; Swanson, David A.

2014-11-01

Purpose: To design and implement a unique training program that uses a phantom-based simulator to teach the process of prostate brachytherapy (PB) quality assurance and improve the quality of education. Methods and Materials: Trainees in our simulator program were practicing radiation oncologists, radiation oncology residents, and fellows of the American Brachytherapy Society. The program emphasized 6 core areas of quality assurance: patient selection, simulation, treatment planning, implant technique, treatment evaluation, and outcome assessment. Using the Iodine 125 ({sup 125}I) preoperative treatment planning technique, trainees implanted their ultrasound phantoms with dummy seeds (ie, seeds with no activity). Pre- and postimplant dosimetric parametersmore » were compared and correlated using regression analysis. Results: Thirty-one trainees successfully completed the simulator program during the period under study. The mean phantom prostate size, number of seeds used, and total activity were generally consistent between trainees. All trainees met the V100 >95% objective both before and after implantation. Regardless of the initial volume of the prostate phantom, trainees' ability to cover the target volume with at least 100% of the dose (V100) was not compromised (R=0.99 pre- and postimplant). However, the V150 had lower concordance (R=0.37) and may better reflect heterogeneity control of the implant process. Conclusions: Analysis of implants from this phantom-based simulator shows a high degree of consistency between trainees and uniformly high-quality implants with respect to parameters used in clinical practice. This training program provides a valuable educational opportunity that improves the quality of PB training and likely accelerates the learning curve inherent in PB. Prostate phantom implantation can be a valuable first step in the acquisition of the required skills to safely perform PB.« less

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

PubMed

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 0.1 ± 0.6 °C, inside and outside the prostate respectively, and the treatment time to within 6.8 min. The simulations also showed excellent agreement in regions of sharp temperature gradients near the transurethral and endorectal cooling devices. Conformal 3D volumes of thermal coagulation can be precisely matched to prostate shapes with transurethral ultrasound devices and active MRI temperature feedback. The accuracy of numerical simulations for MRI-controlled transurethral ultrasound prostate therapy was validated experimentally, reinforcing their utility as an effective treatment planning tool.

Androgen receptor-related diseases: what do we know?

PubMed

Shukla, G C; Plaga, A R; Shankar, E; Gupta, S

2016-05-01

The androgen receptor (AR) and the androgen-AR signaling pathway play a significant role in male sexual differentiation and the development and function of male reproductive and non-reproductive organs. Because of AR's widely varied and important roles, its abnormalities have been identified in various diseases such as androgen insensitivity syndrome, spinal bulbar muscular atrophy, benign prostatic hyperplasia, and prostate cancer. This review provides an overview of the function of androgens and androgen-AR mediated diseases. In addition, the diseases delineated above are discussed with respect to their association with mutations and other post-transcriptional modifications in the AR. Finally, we present an introduction to the potential therapeutic application of most recent pharmaceuticals including miRNAs in prostate cancer that specifically target the transactivation function of the AR at post-transcriptional stages. © 2016 American Society of Andrology and European Academy of Andrology.

Surface-based prostate registration with biomechanical regularization

NASA Astrophysics Data System (ADS)

van de Ven, Wendy J. M.; Hu, Yipeng; Barentsz, Jelle O.; Karssemeijer, Nico; Barratt, Dean; Huisman, Henkjan J.

2013-03-01

Adding MR-derived information to standard transrectal ultrasound (TRUS) images for guiding prostate biopsy is of substantial clinical interest. A tumor visible on MR images can be projected on ultrasound by using MRUS registration. A common approach is to use surface-based registration. We hypothesize that biomechanical modeling will better control deformation inside the prostate than a regular surface-based registration method. We developed a novel method by extending a surface-based registration with finite element (FE) simulation to better predict internal deformation of the prostate. For each of six patients, a tetrahedral mesh was constructed from the manual prostate segmentation. Next, the internal prostate deformation was simulated using the derived radial surface displacement as boundary condition. The deformation field within the gland was calculated using the predicted FE node displacements and thin-plate spline interpolation. We tested our method on MR guided MR biopsy imaging data, as landmarks can easily be identified on MR images. For evaluation of the registration accuracy we used 45 anatomical landmarks located in all regions of the prostate. Our results show that the median target registration error of a surface-based registration with biomechanical regularization is 1.88 mm, which is significantly different from 2.61 mm without biomechanical regularization. We can conclude that biomechanical FE modeling has the potential to improve the accuracy of multimodal prostate registration when comparing it to regular surface-based registration.

Microwave Medical Treatment Apparatus and Method

NASA Technical Reports Server (NTRS)

Arndt, G. Dickey (Inventor); Ngo, Phong H. (Inventor); Carl, James R. (Inventor); George, W. Rflfoul (Inventor)

2005-01-01

Methods, simulations, and apparatus are provided that may be utilized for medical treatments which are especially suitable for treatment of benign prostatic hyperplasia (BPH). In a preferred embodiment, a plurality of separate microwave antennas are utilized to heat prostatic tissue to promote necrosing of the prostatic tissue that relieves the pressure of the prostatic tissue against the urethra as the body reabsorbs the necrosed or dead tissue. By utilizing constructive and destructive interference of the microwave transmission, the energy can be deposited on the tissues to be necrosed while protecting other tissues such as the urethra. Saline injections to alter the conductivity of the tissues may also be used to further focus the energy deposits. A computer simulation is Provided that can be used to Predict the resulting temperature profile produced in the prostatic tissue. By changing the various control features of one or more catheters and the methods of applying microwave energy, a temperature profile can be predicted and produced that is similar to the temperature profile desired for the particular patient.

Comparisons of urodynamic findings and voiding habits in patients with concomitant benign prostatic hyperplasia and detrusor overactivity presenting with or without the symptom of urgency.

PubMed

Tong, Yat-Ching

2007-01-01

The urodynamic findings and voiding habits in patients with concomitant clinical benign prostatic hyperplasia (BPH) and detrusor overactivity (DO) presenting with or without the symptom of urgency were compared. 84 BPH patients with an urodynamic diagnosis of DO by conventional cystometry were included in the study. The patients were grouped according to the presence or absence of the symptom of urgency. The urodynamic findings, urinary diary and clinical information were analyzed. Among the 84 BPH-DO patients, 52 reported the symptom of urgency while 32 did not. There were no significant differences in mean age, International Prostate Symptom Score and flow rate between the two groups. Patients without urgency had a higher incidence of terminal DO and abnormal bladder sensation. The occurrence of unfelt phasic DO was also significantly higher in this group. Sphincter electromyography showed conscious and subconscious sphincter contractions associated with DO. The urinary diary showed lower 24-hour urinary output, smaller bladder functional capacity and average voided volume in the BPH-DO patients without urgency. BPH patients with DO may neglect the symptom of urgency due to abnormal bladder sensation, or negate the symptom by subconscious sphincter contraction to abort the overactivity. Some may avoid the symptom by drinking less fluid and emptying the bladder at a smaller volume. Copyright 2007 S. Karger AG, Basel.

A monte carlo study of restricted diffusion: Implications for diffusion MRI of prostate cancer.

PubMed

Gilani, Nima; Malcolm, Paul; Johnson, Glyn

2017-04-01

Diffusion MRI is used frequently to assess prostate cancer. The prostate consists of cellular tissue surrounding fluid filled ducts. Here, the diffusion properties of the ductal fluid alone were studied. Monte Carlo simulations were used to investigate ductal residence times to determine whether ducts can be regarded as forming a separate compartment and whether ductal radius could determine the Apparent Diffusion Coefficient (ADC) of the ductal fluid. Random walks were simulated in cavities. Average residence times were estimated for permeable cavities. Signal reductions resulting from application of a Stejskal-Tanner pulse sequence were calculated in impermeable cavities. Simulations were repeated for cavities of different radii and different diffusion times. Residence times are at least comparable with diffusion times even in relatively high grade tumors. ADCs asymptotically approach theoretical limiting values. At large radii and short diffusion times, ADCs are similar to free diffusion. At small radii and long diffusion times, ADCs are reduced toward zero, and kurtosis approaches a value of -1.2. Restricted diffusion in cavities of similar sizes to prostate ducts may reduce ductal ADCs. This may contribute to reductions in total ADC seen in prostate cancer. Magn Reson Med 77:1671-1677, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Frequency of Unnecessarily Biopsies among Patients with Suspicion of Prostate Cancer in Syrian Men.

PubMed

Bachour, Dala-Maria; Chahin, Emil; Al-Fahoum, Sahar

2015-01-01

The prevalence of prostate cancer is considered high in many countries, and screening tests are very important in order to detect prostate cancer in its early stages; however false positivity with these screening tests means that a lot of patients undergo unnecessary biopsy, which is an invasive procedure, for the confirmatory test. The purpose of this study was to estimate the frequency of unnecessary biopsy cases in patients referred for prostate biopsy in one of the most important and overload cancer centers in Syria. Retrospective data for a period of four years between January 2009 and December 2012 were collected in Al- Bayrouni University Medical hospital in Damascus, Syria. The patients from whom data were collected were referred to our histopathological department because of elevated prostate specific antigen (PSA) serum or an abnormal digital rectal examination (DRE). All patients underwent prostatic TRUS-guided biopsies. Diagnosis of prostate cancer (PCa) or benign prostatic hyperplasia (BPH) was based on histopathological examination and prostate cancers cases were graded and scored according to the Gleason score system. For the 406 patients referred to biopsy, the mean±SD age was 58.4 ±23.3 years. The mean ± SD PSA level was 49.2±21.5 ng/ ml. Of the total we found 237 patients diagnosed with PCa (58. 4%), 166 patients with BPH (40.9%) and 3 cases were unable to be diagnosed (0.7%) because of biopsy collection errors. Our study shows that a high percentage of patients are undergoing unnecessary biopsy, which suggests that the performed screening tests had a high level of false positive and may need re-evaluation.

The diagnostic test accuracy of rectal examination for prostate cancer diagnosis in symptomatic patients: a systematic review.

PubMed

Jones, Daniel; Friend, Charlotte; Dreher, Andreas; Allgar, Victoria; Macleod, Una

2018-06-02

Prostate cancer is the most common cancer in men in the UK. NICE guidelines on recognition and referral of suspected cancer, recommend performing digital rectal examination (DRE) on patients with urinary symptoms and urgently referring if the prostate feels malignant. However, this is based on the results of one case control study, so it is not known if DRE performed in primary care is an accurate method of detecting prostate cancer. The aim of this review is to ascertain the sensitivity, specificity, positive and negative predictive value of DRE for the detection of prostate cancer in symptomatic patients in primary care. CENTRAL, MEDLINE, EMBASE and CINAHL databases were searched in august 2015 for studies in which a DRE was performed in primary care on symptomatic patients and compared against a reference diagnostic procedure. Four studies were included with a total of 3225 patients. The sensitivity and specificity for DRE as a predictor of prostate cancer in symptomatic patients was 28.6 and 90.7%, respectively. The positive and negative predictive values were 42.3 and 84.2%, respectively. This review found that DRE performed in general practice is accurate, and supports the UK NICE guidelines that patients with a malignant prostate on examination are referred urgently for suspected prostate cancer. Abnormal DRE carried a 42.3% chance of malignancy, above the 3% risk threshold which NICE guidance suggests warrants an urgent referral. However this review questions the benefit of performing a DRE in primary care in the first instance, suggesting that a patient's risk of prostate cancer based on symptoms alone would warrant urgent referral even if the DRE feels normal.

Global Characterization of Protein-Altering Mutations in Prostate Cancer

DTIC Science & Technology

2013-08-01

abnormal signals are marked as horizontal dashed lines on each plot. (A) Average number of AR per nucleus. (B) Average PTEN/CEP10 ratio. doi:10.1371...1060. 20. Hankinson SE, Manson JE, Spiegelman D, Willett WC, Longcope C, et al. (1995) Reproducibility of plasma hormone levels in postmenopausal

A multiparametric magnetic resonance imaging-based risk model to determine the risk of significant prostate cancer prior to biopsy.

PubMed

van Leeuwen, Pim J; Hayen, Andrew; Thompson, James E; Moses, Daniel; Shnier, Ron; Böhm, Maret; Abuodha, Magdaline; Haynes, Anne-Maree; Ting, Francis; Barentsz, Jelle; Roobol, Monique; Vass, Justin; Rasiah, Krishan; Delprado, Warick; Stricker, Phillip D

2017-12-01

To develop and externally validate a predictive model for detection of significant prostate cancer. Development of the model was based on a prospective cohort including 393 men who underwent multiparametric magnetic resonance imaging (mpMRI) before biopsy. External validity of the model was then examined retrospectively in 198 men from a separate institution whom underwent mpMRI followed by biopsy for abnormal prostate-specific antigen (PSA) level or digital rectal examination (DRE). A model was developed with age, PSA level, DRE, prostate volume, previous biopsy, and Prostate Imaging Reporting and Data System (PIRADS) score, as predictors for significant prostate cancer (Gleason 7 with >5% grade 4, ≥20% cores positive or ≥7 mm of cancer in any core). Probability was studied via logistic regression. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap resampling. In all, 393 men had complete data and 149 (37.9%) had significant prostate cancer. While the variable model had good accuracy in predicting significant prostate cancer, area under the curve (AUC) of 0.80, the advanced model (incorporating mpMRI) had a significantly higher AUC of 0.88 (P < 0.001). The model was well calibrated in internal and external validation. Decision analysis showed that use of the advanced model in practice would improve biopsy outcome predictions. Clinical application of the model would reduce 28% of biopsies, whilst missing 2.6% significant prostate cancer. Individualised risk assessment of significant prostate cancer using a predictive model that incorporates mpMRI PIRADS score and clinical data allows a considerable reduction in unnecessary biopsies and reduction of the risk of over-detection of insignificant prostate cancer at the cost of a very small increase in the number of significant cancers missed. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Mechatronics Interface for Computer Assisted Prostate Surgery Training

NASA Astrophysics Data System (ADS)

Altamirano del Monte, Felipe; Padilla Castañeda, Miguel A.; Arámbula Cosío, Fernando

2006-09-01

In this work is presented the development of a mechatronics device to simulate the interaction of the surgeon with the surgical instrument (resectoscope) used during a Transurethral Resection of the Prostate (TURP). Our mechatronics interface is part of a computer assisted system for training in TURP, which is based on a 3D graphics model of the prostate which can be deformed and resected interactively by the user. The mechatronics interface, is the device that the urology residents will manipulate to simulate the movements performed during surgery. Our current prototype has five degrees of freedom, which are enough to have a realistic simulation of the surgery movements. Two of these degrees of freedom are linear, to determinate the linear displacement of the resecting loop and the other three are rotational to determinate three directions and amounts of rotation.

Role of GPR30 in estrogen-induced prostate epithelial apoptosis and benign prostatic hyperplasia.

PubMed

Yang, Deng-Liang; Xu, Jia-Wen; Zhu, Jian-Guo; Zhang, Yi-Lin; Xu, Jian-Bang; Sun, Qing; Cao, Xiao-Nian; Zuo, Wu-Lin; Xu, Ruo-Shui; Huang, Jie-Hong; Jiang, Fu-Neng; Zhuo, Yang-Jia; Xiao, Bai-Quan; Liu, Yun-Zhong; Yuan, Dong-Bo; Sun, Zhao-Lin; He, Hui-Chan; Lun, Zhao-Rong; Zhong, Wei-De; Zhou, Wen-Liang

2017-06-03

Several studies have implicated estrogen and the estrogen receptor (ER) in the pathogenesis of benign prostatic hyperplasia (BPH); however, the mechanism underlying this effect remains elusive. In the present study, we demonstrated that estrogen (17β-estradiol, or E2)-induced activation of the G protein-coupled receptor 30 (GPR30) triggered Ca 2+ release from the endoplasmic reticulum, increased the mitochondrial Ca 2+ concentration, and thus induced prostate epithelial cell (PEC) apoptosis. Both E2 and the GPR30-specific agonist G1 induced a transient intracellular Ca 2+ release in PECs via the phospholipase C (PLC)-inositol 1, 4, 5-triphosphate (IP 3 ) pathway, and this was abolished by treatment with the GPR30 antagonist G15. The release of cytochrome c and activation of caspase-3 in response to GPR30 activation were observed. Data generated from the analysis of animal models and human clinical samples indicate that treatment with the GPR30 agonist relieves testosterone propionate (TP)-induced prostatic epithelial hyperplasia, and that the abundance of GPR30 is negatively associated with prostate volume. On the basis of these results, we propose a novel regulatory mechanism whereby estrogen induces the apoptosis of PECs via GPR30 activation. Inhibition of this activation is predicted to lead to abnormal PEC accumulation, and to thereby contribute to BPH pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Acoustic-based proton range verification in heterogeneous tissue: simulation studies

NASA Astrophysics Data System (ADS)

Jones, Kevin C.; Nie, Wei; Chu, James C. H.; Turian, Julius V.; Kassaee, Alireza; Sehgal, Chandra M.; Avery, Stephen

2018-01-01

Acoustic-based proton range verification (protoacoustics) is a potential in vivo technique for determining the Bragg peak position. Previous measurements and simulations have been restricted to homogeneous water tanks. Here, a CT-based simulation method is proposed and applied to a liver and prostate case to model the effects of tissue heterogeneity on the protoacoustic amplitude and time-of-flight range verification accuracy. For the liver case, posterior irradiation with a single proton pencil beam was simulated for detectors placed on the skin. In the prostate case, a transrectal probe measured the protoacoustic pressure generated by irradiation with five separate anterior proton beams. After calculating the proton beam dose deposition, each CT voxel’s material properties were mapped based on Hounsfield Unit values, and thermoacoustically-generated acoustic wave propagation was simulated with the k-Wave MATLAB toolbox. By comparing the simulation results for the original liver CT to homogenized variants, the effects of heterogeneity were assessed. For the liver case, 1.4 cGy of dose at the Bragg peak generated 50 mPa of pressure (13 cm distal), a 2×  lower amplitude than simulated in a homogeneous water tank. Protoacoustic triangulation of the Bragg peak based on multiple detector measurements resulted in 0.4 mm accuracy for a δ-function proton pulse irradiation of the liver. For the prostate case, higher amplitudes are simulated (92-1004 mPa) for closer detectors (<8 cm). For four of the prostate beams, the protoacoustic range triangulation was accurate to  ⩽1.6 mm (δ-function proton pulse). Based on the results, application of protoacoustic range verification to heterogeneous tissue will result in decreased signal amplitudes relative to homogeneous water tank measurements, but accurate range verification is still expected to be possible.

Testosterone and dihydrotestosterone levels in the transition zone correlate with prostate volume.

PubMed

Pejčić, Tomislav; Tosti, Tomislav; Tešić, Živoslav; Milković, Borivoj; Dragičević, Dejan; Kozomara, Milutin; Čekerevac, Milica; Džamić, Zoran

2017-07-01

There is still no consensus regarding intraprostatic androgen levels and the accumulation of androgens in the hyperplastic prostatic tissue. The current opinion is that intraprostatic dihydrotestosterone (DHT) concentrations are maintained but not elevated in benign prostatic hyperplasia (BPH), while there is no similar data concerning intraprostatic testosterone (T). Tissue T (tT) and tissue DHT (tDHT) concentration were determined in 93 patients scheduled for initial prostate biopsy. The criteria for biopsy were abnormal DRE and/or PSA > 4 ng/mL. Total prostate volume (TPV) was determined by transrectal ultrasound (TRUS). During TRUS- guided prostate biopsy, 10-12 samples were collected from the peripheral zone (PZ) and two additional samples were collected from the transition zone (TZ). The samples from the TZ were immediately frozen in liquid nitrogen at -70°C, and transported for tissue androgen determination, using liquid chromatography mass spectrometry (LC-MS). Pathological analysis revealed that prostate cancer (PCa) was present in 45 and absent in 48 patients. In the whole group, there were 42 men with small prostate (TPV < 30 mL) and 51 with enlarged prostate (TPV ≥ 31 mL). The overall average tT level was 0.79 ± 0.66 ng/g, while the average tDHT level was 10.27 ± 7.15 ng/g. There were no differences in tT and tDHT level in prostates with and without PCa. However, tT and tDHT levels were significantly higher in larger, than in smaller prostates (tT: 1.05 ± 0.75 and 0.46 ± 0.29 ng/g, and tDHT: 15.0 ± 6.09 and 4.51 ± 2.75 ng/g, respectively). There were strong correlations between tT and TPV (r = 0.71), and tDHT and TPV (r = 0.74). The present study confirmed that both T and DHT accumulated in the stroma of enlarged prostates; the degree of accumulation correlated with prostate volume. © 2017 Wiley Periodicals, Inc.

Laser Illumination Modality of Photoacoustic Imaging Technique for Prostate Cancer

NASA Astrophysics Data System (ADS)

Peng, Dong-qing; Peng, Yuan-yuan; Guo, Jian; Li, Hui

2016-02-01

Photoacoustic imaging (PAI) has recently emerged as a promising imaging technique for prostate cancer. But there was still a lot of challenge in the PAI for prostate cancer detection, such as laser illumination modality. Knowledge of absorbed light distribution in prostate tissue was essential since the distribution characteristic of absorbed light energy would influence the imaging depth and range of PAI. In order to make a comparison of different laser illumination modality of photoacoustic imaging technique for prostate cancer, optical model of human prostate was established and combined with Monte Carlo simulation method to calculate the light absorption distribution in the prostate tissue. Characteristic of light absorption distribution of transurethral and trans-rectal illumination case, and of tumor at different location was compared with each other.The relevant conclusions would be significant for optimizing the light illumination in a PAI system for prostate cancer detection.

The Difficult Task of Diagnosing Prostate Cancer Metastases on Dry Bone.

PubMed

Castoldi, Elisa; Cappella, Annalisa; Gibelli, Daniele; Sforza, Chiarella; Cattaneo, Cristina

2018-05-01

The interpretation of pathology on skeletal remains is mandatory for implementing the biological profile and for disease recognition. Prostate cancer is one of the most common tumors, with a high preference for the skeleton as a primary site of metastasis. Its diagnosis on bone is however still ambiguous, due to its "osteoblastic" and resorptive manifestation. This study investigates distribution and appearance of prostate cancer metastases on dry bone on six known cases (selected from the Milano Cemetery Skeletal Collection) and one healthy individual. A macroscopic inspection was performed highlighting the abnormalities observed, describing location, shape, dimension, and aspect. A great amount of proliferative and mixed lesions was noticed, but also cases of pure lytic lesions were displayed. The multiple appearances of the manifestations observed display the difficulty in correctly identifying such a pathology, but also the potential and advantages provided by investigating a study sample with known antemortem history. © 2017 American Academy of Forensic Sciences.

Simulation of a pulsed light propagation in the prostate phantom

NASA Astrophysics Data System (ADS)

Guo, Jian; Li, Zhifang; Xie, Wenming; Chen, Haiyu; Weng, Guo-Xing; Li, Hui

2014-09-01

In recent years, more and more Americans are diagnosed with prostate cancer, and the current detection methods still have some disadvantages. Photoacoustic imaging, as a new non-invasive imaging technique, has the capable of imaging complex tissue and owns the ability of early tumor imaging. And the photoacoustic signal of the tumor is bound up with its light energy distribution. In this paper, Monte Carlo method was used to simulate the light propagation in the prostate phantom. The pictures of light energy distribution by the irradiation of a pulsed laser were obtained. With the pulsed laser, according to the absorption coefficient of tumor, the local energy temporal changes in prostate can be illustrated. As we known, the local photoacoustic signal has a relationship with the change of light energy. Then we can see the influence of photoacoustic signal under the changes of the absorption coefficient of tumor.

Modulus reconstruction from prostate ultrasound images using finite element modeling

NASA Astrophysics Data System (ADS)

Yan, Zhennan; Zhang, Shaoting; Alam, S. Kaisar; Metaxas, Dimitris N.; Garra, Brian S.; Feleppa, Ernest J.

2012-03-01

In medical diagnosis, use of elastography is becoming increasingly more useful. However, treatments usually assume a planar compression applied to tissue surfaces and measure the deformation. The stress distribution is relatively uniform close to the surface when using a large, flat compressor but it diverges gradually along tissue depth. Generally in prostate elastography, the transrectal probes used for scanning and compression are cylindrical side-fire or rounded end-fire probes, and the force is applied through the rectal wall. These make it very difficult to detect cancer in prostate, since the rounded contact surfaces exaggerate the non-uniformity of the applied stress, especially for the distal, anterior prostate. We have developed a preliminary 2D Finite Element Model (FEM) to simulate prostate deformation in elastography. The model includes a homogeneous prostate with a stiffer tumor in the proximal, posterior region of the gland. A force is applied to the rectal wall to deform the prostate, strain and stress distributions can be computed from the resultant displacements. Then, we assume the displacements as boundary condition and reconstruct the modulus distribution (inverse problem) using linear perturbation method. FEM simulation shows that strain and strain contrast (of the lesion) decrease very rapidly with increasing depth and lateral distance. Therefore, lesions would not be clearly visible if located far away from the probe. However, the reconstructed modulus image can better depict relatively stiff lesion wherever the lesion is located.

Transperineal ultrasound-guided implantation of electromagnetic transponders in the prostatic fossa for localization and tracking during external beam radiation therapy.

PubMed

Garsa, Adam A; Verma, Vivek; Michalski, Jeff M; Gay, Hiram A

2014-01-01

To describe a transperineal ultrasound-guided technique for implantation of electromagnetic transponders into the prostatic fossa. Patients were placed in the dorsal lithotomy position, and local anesthetic was administered. On ultrasound, the bladder, urethra, vesicourethral anastomosis, rectum, and the prostatic fossa were carefully identified. Three transponders were implanted into the prostatic fossa under ultrasound guidance in a triangular configuration and implantation was verified by fluoroscopy. Patients underwent computed tomography (CT) simulation approximately 1 week later. All patients in this study were subsequently treated with intensity modulated radiation therapy (IMRT) to the prostatic fossa. From 2008 to 2012, 180 patients received transperineal implantation of electromagnetic transponders into the prostatic fossa and subsequently received IMRT. There were no cases of severe hematuria or rectal bleeding requiring intervention. There were no grade 3 or 4 toxicities. Three patients (1.7%) had a transponder missing on the subsequent CT simulation. Thirteen patients (7.3%) had transponder migration with a geometric residual that exceeded 2 mm for 3 consecutive days (5.6%) or rotation that exceeded 10 degrees for 5 consecutive days (1.7%). These patients underwent a resimulation CT scan to identify the new transponder coordinates. A transperineal technique for implantation of electromagnetic transponders into the prostatic fossa is safe and well tolerated, with no severe toxicity after implantation. There is a low rate of transponder loss or migration.

[Efficacy and safety of Longjintonglin Capsule for the treatment of type III prostatitis].

PubMed

Shang, Xue-Jun; Geng, Qiang; Duan, Jian-Min; Zheng, De-Quan; Xie, Lei; Guo, Jun

2014-12-01

To study the therapeutic effect and safety of Longjintonglin Capsule in the treatment of type III prostatitis (chronic prostatitis/chronic pelvic pain syndrome, CP/CPPS). We selected 240 patients with type III prostatitis according to the diagnostic standards of the American National Institute of Health (NIH) and treated them with Longjintonglin Capsule orally 3 capsules once tid for 12 weeks. Based on the NIH chronic prostatitis symptom index (NIH-CPSI), traditional Chinese medicine (TCM) syndrome score, and leukocyte count in the expressed prostatic secretion (EPS), we evaluated the results of treatment. Totally 238 patients completed the treatment, including 108 IIIA and 120 III B prostatitis cases. Before and after 4, 8, and 12 weeks of treatment, the total NIH-CPSI scores were 23.12 ± 6.99, 18.22 ± 6.39, 14.12 ± 5.88, and 12.36 ± 6.04 (P < 0.01) in the IIIA prostatitis patients and 22.01 ± 6.28, 17.56 ± 5.89, 13.67 ± 5.18, and 11.45 ± 5.22 in the III prostatitis patients (P < 0.01), the TCM syndrome scores were 52.12 ± 13.08, 48.13 ± 12.11, 43.05 ± 11.19, and 40.78 ± 10. 59 in the former (P < 0.01) and 53.02 ± 12.12, 49.32 ± 12.78, 44.01 ± 11.79, and 39.67 ± 10.26 in the latter (P < 0.01), and the leukocyte counts were 26.09 ± 21.55, 23.02 ± 18.61, 18.25 ± 17.79, and 15.36 ± 16.38 in the IIIA cases (P < 0.01). Neither abnormalities in liver and renal function nor obvious adverse events were observed during the experiment. Longjintonglin Capsule, with its advantages of safety, effectiveness, and no obvious adverse reactions in the treatment of type III prostatitis, deserves to be recommended for clinical application.

Virtual reality simulator for training on photoselective vaporization of the prostate with 980 nm diode laser and learning curve of the technique.

PubMed

Angulo, J C; Arance, I; García-Tello, A; Las Heras, M M; Andrés, G; Gimbernat, H; Lista, F; Ramón de Fata, F

2014-09-01

The utility of a virtual reality simulator for training of the photoselective vaporization of the prostate with diode laser was studied. Two experiments were performed with a simulator (VirtaMed AG, Zürich, Switzerland) with software for specific training in prostate vaporization in contact mode with Twister fiber (Biolitec AG, Jena, German). Eighteen surgeons performed ablation of the prostate (55 cc) twice and compared the score obtained (190 points efficacy and 80 safety) in the second one of them by experience groups (medical students, residents, specialists). They also performed a spatial orientation test with scores of 0 to 6. After, six of these surgeons repeated 15 ablations of the prostate (55 and 70 ml). Improvement of the parameters obtained was evaluated to define the learning curve and how experience, spatial orientation skills and type of sequences performed affects them. Global efficacy and safety score was different according to the grade of experience (P=.005). When compared by pairs, specialist-student differences were detected (p=0.004), but not specialist-resident (P=.12) or resident-student (P=.2). Regarding efficacy of the procedure, specialist-student (p=0.0026) and resident-student (P=.08) differences were detected. The different partial indicators in terms of efficacy were rate of ablation (P=.01), procedure time (P=.03) and amount of unexposed capsule (p=0.03). Differences were not observed between groups in safety (P=.5). Regarding the learning curve, percentage median on the total score exceeded 90% after performing 4 procedures for prostates of 55 ml and 10 procedures for prostate glands of 70 ml. This course was not modified by previous experience (resident-specialist; P=.6). However, it was modified according to the repetition sequence (progressive-random; P=.007). Surgeons whose spatial orientation was less than the median of the group (value 2.5) did not surpass 90% of the score in spite of repetition of the procedure. Simulation for ablation of the prostate with contact diode laser is a good learning model with discriminative validity, as it correlates the metric results with levels of experience and sills. The sequential repetition of the procedure on growing levels of difficulty favors learning. Copyright © 2014 AEU. Published by Elsevier Espana. All rights reserved.

The economic effect of using magnetic resonance imaging and magnetic resonance ultrasound fusion biopsy for prostate cancer diagnosis.

PubMed

Hutchinson, Ryan C; Costa, Daniel N; Lotan, Yair

2016-07-01

Prostate magnetic resonance imaging (MRI) is a maturing imaging modality that has been used to improve detection and staging of prostate cancer. The goal of this review is to evaluate the economic effect of the use of MRI and MRI fusion in the diagnosis of prostate cancer. A literature review was used to identify articles regarding efficacy and cost of MRI and MRI-guided biopsies. There are currently a limited number of studies evaluating cost of incorporating MRI into clinical practice. These studies are primarily models projecting cost estimates based on meta-analyses of the literature. There is considerable variance in the effectiveness of MRI-guided biopsies, both cognitive and fusion, based on user experience, type of MRI (3T vs. 1.5T), use of endorectal coil and type of scoring system for abnormalities such that there is still potential for improvement in accuracy. There is also variability in assumed costs of incorporating MRI into clinical practice. The addition of MRI to the diagnostic algorithm for prostate cancer has caused a shift in how we understand the disease and in what tumors are found on initial and repeat biopsies. Further risk stratification may allow more men to pursue noncurative therapy, which in and of itself is cost-effective in properly selected men. As prostate cancer care comes under increasing scrutiny on a national level, there is pressure on providers to be more accurate in their diagnoses. This in turn can lead to additional testing including Multiparametric MRI, which adds upfront cost. Whether the additional cost of prostate MRI is warranted in detection of prostate cancer is an area of intense research. Copyright © 2016 Elsevier Inc. All rights reserved.

Investigation of scattering coefficients and anisotropy factors of human cancerous and normal prostate tissues using Mie theory

NASA Astrophysics Data System (ADS)

Pu, Yang; Chen, Jun; Wang, Wubao

2014-02-01

The scattering coefficient, μs, the anisotropy factor, g, the scattering phase function, p(θ), and the angular dependence of scattering intensity distributions of human cancerous and normal prostate tissues were systematically investigated as a function of wavelength, scattering angle and scattering particle size using Mie theory and experimental parameters. The Matlab-based codes using Mie theory for both spherical and cylindrical models were developed and applied for studying the light propagation and the key scattering properties of the prostate tissues. The optical and structural parameters of tissue such as the index of refraction of cytoplasm, size of nuclei, and the diameter of the nucleoli for cancerous and normal human prostate tissues obtained from the previous biological, biomedical and bio-optic studies were used for Mie theory simulation and calculation. The wavelength dependence of scattering coefficient and anisotropy factor were investigated in the wide spectral range from 300 nm to 1200 nm. The scattering particle size dependence of μs, g, and scattering angular distributions were studied for cancerous and normal prostate tissues. The results show that cancerous prostate tissue containing larger size scattering particles has more contribution to the forward scattering in comparison with the normal prostate tissue. In addition to the conventional simulation model that approximately considers the scattering particle as sphere, the cylinder model which is more suitable for fiber-like tissue frame components such as collagen and elastin was used for developing a computation code to study angular dependence of scattering in prostate tissues. To the best of our knowledge, this is the first study to deal with both spherical and cylindrical scattering particles in prostate tissues.

Evaluation of the learning curve for thulium laser enucleation of the prostate with the aid of a simulator tool but without tutoring: comparison of two surgeons with different levels of endoscopic experience.

PubMed

Saredi, Giovanni; Pirola, Giacomo Maria; Pacchetti, Andrea; Lovisolo, Jon Alexander; Borroni, Giacomo; Sembenini, Federico; Marconi, Alberto Mario

2015-06-09

The aim of this study was to determine the learning curve for thulium laser enucleation of the prostate (ThuLEP) for two surgeons with different levels of urological endoscopic experience. From June 2012 to August 2013, ThuLEP was performed on 100 patients in our institution. We present the results of a prospective evaluation during which we analyzed data related to the learning curves for two surgeons of different levels of experience. The prostatic adenoma volumes ranged from 30 to 130 mL (average 61.2 mL). Surgeons A and B performed 48 and 52 operations, respectively. Six months after surgery, all patients were evaluated with the International Prostate Symptom Score questionnaire, uroflowmetry, and prostate-specific antigen test. Introduced in 2010, ThuLEP consists of blunt enucleation of the prostatic apex and lobes using the sheath of the resectoscope. This maneuver allows clearer visualization of the enucleation plane and precise identification of the prostatic capsule. These conditions permit total resection of the prostatic adenoma and coagulation of small penetrating vessels, thereby reducing the laser emission time. Most of the complications in this series were encountered during morcellation, which in some cases was performed under poor vision because of venous bleeding due to surgical perforation of the capsule during enucleation. Based on this analysis, we concluded that it is feasible for laser-naive urologists with endoscopic experience to learn to perform ThuLEP without tutoring. Those statements still require further validation in larger multicentric study cohort by several surgeon. The main novelty during the learning process was the use of a simulator that faithfully reproduced all of the surgical steps in prostates of various shapes and volumes.

Tissue-scale, personalized modeling and simulation of prostate cancer growth

NASA Astrophysics Data System (ADS)

Lorenzo, Guillermo; Scott, Michael A.; Tew, Kevin; Hughes, Thomas J. R.; Zhang, Yongjie Jessica; Liu, Lei; Vilanova, Guillermo; Gomez, Hector

2016-11-01

Recently, mathematical modeling and simulation of diseases and their treatments have enabled the prediction of clinical outcomes and the design of optimal therapies on a personalized (i.e., patient-specific) basis. This new trend in medical research has been termed “predictive medicine.” Prostate cancer (PCa) is a major health problem and an ideal candidate to explore tissue-scale, personalized modeling of cancer growth for two main reasons: First, it is a small organ, and, second, tumor growth can be estimated by measuring serum prostate-specific antigen (PSA, a PCa biomarker in blood), which may enable in vivo validation. In this paper, we present a simple continuous model that reproduces the growth patterns of PCa. We use the phase-field method to account for the transformation of healthy cells to cancer cells and use diffusion-reaction equations to compute nutrient consumption and PSA production. To accurately and efficiently compute tumor growth, our simulations leverage isogeometric analysis (IGA). Our model is shown to reproduce a known shape instability from a spheroidal pattern to fingered growth. Results of our computations indicate that such shift is a tumor response to escape starvation, hypoxia, and, eventually, necrosis. Thus, branching enables the tumor to minimize the distance from inner cells to external nutrients, contributing to cancer survival and further development. We have also used our model to perform tissue-scale, personalized simulation of a PCa patient, based on prostatic anatomy extracted from computed tomography images. This simulation shows tumor progression similar to that seen in clinical practice.

Prostate cancer: how assessment of QoL can improve delivery of care.

PubMed

Brown, Michelle

Prostate cancer treatments often affect quality of life and problems may present at any point during treatment. Measuring and identifying issues of quality of life (QoL) may create an opportunity for the patient to discuss problems and induce information transfer from health professional to patient and vice versa. Many practitioners already assess QoL in patients with prostate cancer because treatment for the disease can have a dramatic impact on lifestyle. QoL may facilitate a more holistic approach to patient care. Using a QoL assessment tool may promote and enhance the current service provision and aid identification of bothersome side-effects, for example loss of libido, gynaecomastia (i.e. abnormal over-development of the breasts in a man), and hot flushes. The Functional Assessment of Cancer Therapy-Prostate scale (FACT-P) (Cella et al, 1993) is a prostate-specific QoL assessment tool, which can be self-administered and takes little time to complete. This may be a useful tool in the ongoing management of patients with advanced prostate cancer. With the emphasis on quality of service for cancer patients (Department of Health (DH), 2000; DH, 2007a; National Health Service Improvement, 2009), it is paramount that health professionals continually examine practice and the quality of the service delivered. Addressing QoL issues for the patient with cancer should be a priority. This article will outline the significant side-effects that a patient with advanced prostate cancer may sustain and attempts to indicate how QoL assessment tools may contribute to care management and delivery.

Expression of hemidesmosomal and extracellular matrix proteins by normal and malignant human prostate tissue.

PubMed Central

Nagle, R. B.; Hao, J.; Knox, J. D.; Dalkin, B. L.; Clark, V.; Cress, A. E.

1995-01-01

The progression of prostate carcinoma may be influenced by the biochemical nature of the basal lamina surrounding the primary carcinoma cells. As a first step toward understanding this process, the composition and structure of the basal lamina in normal prostate, prostatic intraepithelial neoplasia, and human carcinoma were determined. In addition, a comparison was made between the attachments of the normal basal cell to its underlying basal lamina and those made by primary prostate carcinoma. The normal basal cells form both focal adhesions and hemidesmosomal-like structures as observed by transmission electron microscopy. The normal basal cells exhibited a polarized distribution of hemidesmosomal associated proteins including BP180, BP230, HD1, plectin, laminin-gamma 2(B2t), collagen VII, and the corresponding integrin laminin receptors alpha 6 beta 1 and alpha 6 beta 4. The expression and distribution pattern of these proteins were retained in the prostate intraepithelial neoplasia lesions. In contrast, the carcinoma cells uniformly lacked hemidesmosomal structures, the integrin alpha 6 beta 4, BP180, laminin-gamma 2 (B2t), and collagen VII but did express BP230 (30%), plectin, HD1 (15%), and the integrin laminin receptors alpha 3 beta 1 and alpha 6 beta 1. These results suggest that, although a detectable basal lamina structure is present in carcinoma, its composition and cellular attachments are abnormal. The loss of critical cellular attachments may play a role in influencing the progression potential of prostate carcinoma. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7778688

Fast Conformal Thermal Ablation in the Prostate with Transurethral Multi-Sectored Ultrasound Devices and MR Guidance

NASA Astrophysics Data System (ADS)

Kinsey, Adam M.; Diederich, Chris J.; Nau, William H.; Ross, Anthony B.; Pauly, Kim Butts; Rieke, Viola; Sommer, Graham

2007-05-01

Transurethral ultrasound applicators incorporating an array of multisectored tubular transducers were evaluated in theoretical simulations and in vivo canine prostates under MR guidance as a method for fast, conformal thermal therapy of the prostate. Comprehensive simulations with a biothermal model investigated the effect on lesion creation of sector size, perfusion, treatment time, rectal cooling, prostate target dimensions, and feedback controller parameters (maximum temperature, pilot points at boundary, update times). In vivo canine prostates (n = 4) were treated with trisectored ultrasound transducers (3 mm OD) under MR temperature monitoring to contour the ablation zone (>52 C for 1-2 min) to the boundary of the prostate. Contiguous thermal lesions extended 2 cm in radius from the urethra in less than 15 min and independent sector control simultaneously allowed for conformal treatment in the angular dimension. Experiments investigated sequential translation of the transducer assembly within the catheter for tailoring heat treatments to different partitions in the prostate (base, apex) without changing the initial setup. This treatment method offered greater lesion shape control in three dimensions and slightly lengthened the overall treatment time. The MR temperature images correlated with post-treatment histology and accurately controlled the heating to the target boundary. MR-based control of transurethral ultrasound devices appeared more practical with multisectored transducers compared to rotating curvilinear and planar applicators due to less stringent requirements on spatial and temporal MR parameters. This study demonstrated the applicability of these devices in the prostate for anterior-lateral BPH treatment, and whole gland or quadrant target volumes for cancer treatment.

Evaluation of Genomic Instability in the Abnormal Prostate

DTIC Science & Technology

2007-12-01

Mehrotra, J., Varde, S., Wang, H., Chiu, H., Vargo, J., Gray , K., Nagle, R.B., Neri, J.R., Mazumder, A. (2007) Prostate 68, 152-60. Appendix A...GSTP-1 Reverse 5’-GCC CCA ATA CTA AAT CAC GAC G-3’ GSTP-1 Probe 5’-6-FAM-CGG TCG ACG TTC GGG GTG TAG CG-6-TAMSp-3’ RassF1A Forward 5’-GCG TTG AAG...GAA CCA AAA CGC TCC CCA T-3’ APC Reverse 5’-TTA TAT GTC GGT TAC GTG CGT TTA TAT-3’ APC Probe 5’-6-FAM-CCC GTC GAA AAC CCG CCG ATT A-6-TAMSp-3

Decreased fucosylated PSA as a urinary marker for high Gleason score prostate cancer.

PubMed

Fujita, Kazutoshi; Hayashi, Takuji; Matsuzaki, Kyosuke; Nakata, Wataru; Masuda, Mika; Kawashima, Atsunari; Ujike, Takeshi; Nagahara, Akira; Tsuchiya, Mutsumi; Kobayashi, Yuka; Nojima, Satoshi; Uemura, Motohide; Morii, Eiichi; Miyoshi, Eiji; Nonomura, Norio

2016-08-30

Fucosylation is an important oligosaccharide modification associated with cancer and inflammation. We investigated whether urinary fucosylated PSA (Fuc-PSA) levels could be used for the detection of high Gleason score prostate cancer. Urine samples were collected from men with abnormal digital rectal examination findings or elevated serum PSA levels, before prostate biopsy. Lectin-antibody ELISA was used to quantify the Lewis-type or core-type fucosylated PSA (PSA-AAL) and core-type fucosylated PSA (PSA-PhoSL) in the urine samples. Both types of urinary Fuc-PSA were significantly decreased in the men with prostate cancer compared with the men whose biopsies were negative for cancer (P = 0.026 and P < 0.001, respectively). Both were also significantly associated with the Gleason scores of the biopsy specimens (P = 0.001 and P < 0.001, respectively). Multivariate analysis showed that PSA density, urinary PSA-AAL, and urinary PSA-PhoSL were independent predictors of high Gleason score prostate cancer. The area under the receiver-operator characteristic curve (AUC) value for the prediction of cancers of Gleason score ≥ 7 was 0.69 for urinary PSA-AAL and 0.72 for urinary PSA-PhoSL. In contrast, the AUC value was 0.59 for serum PSA, 0.63 for PSA density, and 0.58 for urinary PSA. In conclusion, a decreased urinary Fuc-PSA level is a potential marker for the detection of high Gleason score prostate cancer.

Decreased fucosylated PSA as a urinary marker for high Gleason score prostate cancer

PubMed Central

Fujita, Kazutoshi; Hayashi, Takuji; Matsuzaki, Kyosuke; Nakata, Wataru; Masuda, Mika; Kawashima, Atsunari; Ujike, Takeshi; Nagahara, Akira; Tsuchiya, Mutsumi; Kobayashi, Yuka; Nojima, Satoshi; Uemura, Motohide; Morii, Eiichi; Miyoshi, Eiji; Nonomura, Norio

2016-01-01

Fucosylation is an important oligosaccharide modification associated with cancer and inflammation. We investigated whether urinary fucosylated PSA (Fuc-PSA) levels could be used for the detection of high Gleason score prostate cancer. Urine samples were collected from men with abnormal digital rectal examination findings or elevated serum PSA levels, before prostate biopsy. Lectin-antibody ELISA was used to quantify the Lewis-type or core-type fucosylated PSA (PSA-AAL) and core-type fucosylated PSA (PSA-PhoSL) in the urine samples. Both types of urinary Fuc-PSA were significantly decreased in the men with prostate cancer compared with the men whose biopsies were negative for cancer (P = 0.026 and P < 0.001, respectively). Both were also significantly associated with the Gleason scores of the biopsy specimens (P = 0.001 and P < 0.001, respectively). Multivariate analysis showed that PSA density, urinary PSA-AAL, and urinary PSA-PhoSL were independent predictors of high Gleason score prostate cancer. The area under the receiver-operator characteristic curve (AUC) value for the prediction of cancers of Gleason score ≥ 7 was 0.69 for urinary PSA-AAL and 0.72 for urinary PSA-PhoSL. In contrast, the AUC value was 0.59 for serum PSA, 0.63 for PSA density, and 0.58 for urinary PSA. In conclusion, a decreased urinary Fuc-PSA level is a potential marker for the detection of high Gleason score prostate cancer. PMID:27494861

Dosimetric effects of patient rotational setup errors on prostate IMRT treatments

NASA Astrophysics Data System (ADS)

Fu, Weihua; Yang, Yong; Li, Xiang; Heron, Dwight E.; Saiful Huq, M.; Yue, Ning J.

2006-10-01

The purpose of this work is to determine dose delivery errors that could result from systematic rotational setup errors (ΔΦ) for prostate cancer patients treated with three-phase sequential boost IMRT. In order to implement this, different rotational setup errors around three Cartesian axes were simulated for five prostate patients and dosimetric indices, such as dose-volume histogram (DVH), tumour control probability (TCP), normal tissue complication probability (NTCP) and equivalent uniform dose (EUD), were employed to evaluate the corresponding dosimetric influences. Rotational setup errors were simulated by adjusting the gantry, collimator and horizontal couch angles of treatment beams and the dosimetric effects were evaluated by recomputing the dose distributions in the treatment planning system. Our results indicated that, for prostate cancer treatment with the three-phase sequential boost IMRT technique, the rotational setup errors do not have significant dosimetric impacts on the cumulative plan. Even in the worst-case scenario with ΔΦ = 3°, the prostate EUD varied within 1.5% and TCP decreased about 1%. For seminal vesicle, slightly larger influences were observed. However, EUD and TCP changes were still within 2%. The influence on sensitive structures, such as rectum and bladder, is also negligible. This study demonstrates that the rotational setup error degrades the dosimetric coverage of target volume in prostate cancer treatment to a certain degree. However, the degradation was not significant for the three-phase sequential boost prostate IMRT technique and for the margin sizes used in our institution.

Dosimetric effects of endorectal balloons on intensity-modulated radiation therapy plans for prostate cancer

NASA Astrophysics Data System (ADS)

Kim, Jae-Sung; Chung, Jin-Beom; Kim, In-Ah; Eom, Keun-Yong

2013-10-01

We used an endorectal balloon (ERB) for prostate immobilization during intensity-modulated radiotherapy (IMRT) for prostate cancer treatment. To investigate the dosimetric effects of ERB-filling materials, we changed the ERB Hounsfield unit (HU) from 0 to 1000 HU in 200-HU intervals to simulate the various ERB fillings; 0 HU simulated a water-filled ERB, and 1000 HU simulated the densest material-filled ERB. Dosimetric data (coverage, homogeneity, conformity, maximal dose, and typical volume dose) for the tumor and the organs at risk (OARs) were evaluated in prostate IMRT treatment plans with 6-MV and 15-MV beams. The tumor coverage appeared to differ by approximately 1%, except for the clinical target volume (CTV) V100% and the planning target volume (PTV) V100%. The largest difference for the various ERB fillings was observed in the PTV V100%. In spite of increasing HU, the prostate IMRT plans at both energies had relatively low dosimetric effects on the PTV and the CTV. However, the maximal and the typical volume doses (D25%, D30%, and D50%) to the rectal wall and the bladder increased with increasing HU. For an air-filled ERB, the maximal doses to the rectal wall and the monitor units were lower than the corresponding values for the water-filled and the densest material-filled ERBs. An air-filled ERB spared the rectal wall because of its dosimetric effect. Thus, we conclude that the use of an air-filled ERB provides a dosimetric benefit to the rectal wall without a loss of target coverage and is an effective option for prostate IMRT treatment.

Metabolic syndrome and prostate abnormalities in male subjects of infertile couples

PubMed Central

Lotti, Francesco; Corona, Giovanni; Vignozzi, Linda; Rossi, Matteo; Maseroli, Elisa; Cipriani, Sarah; Gacci, Mauro; Forti, Gianni; Maggi, Mario

2014-01-01

No previous study has evaluated systematically the relationship between metabolic syndrome (MetS) and prostate-related symptoms and signs in young infertile men. We studied 171 (36.5 ± 8.3-years-old) males of infertile couples. MetS was defined based on the National Cholesterol Education Program Third Adult Treatment Panel. All men underwent hormonal (including total testosterone (TT) and insulin), seminal (including interleukin-8 (IL-8), seminal plasma IL-8 (sIL-8)), scrotal and transrectal ultrasound evaluations. Because we have previously assessed correlations between MetS and scrotal parameters in a larger cohort of infertile men, here, we focused on transrectal features. Prostate-related symptoms were assessed using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and the International Prostate Symptom Score (IPSS). Twenty-two subjects fulfilled MetS criteria. In an age-adjusted logistic ordinal model, insulin levels increased as a function of MetS components (Wald = 29.5, P < 0.0001) and showed an inverse correlation with TT (adjusted r = -0.359, P< 0.0001). No association between MetS and NIH-CPSI or IPSS scores was observed. In an age-, TT-, insulin-adjusted logistic ordinal model, an increase in number of MetS components correlated negatively with normal sperm morphology (Wald = 5.59, P< 0.02) and positively with sIL-8 levels (Wald = 4.32, P < 0.05), which is a marker of prostate inflammation, with prostate total and transitional zone volume assessed using ultrasound (Wald = 17.6 and 12.5, both P < 0.0001), with arterial peak systolic velocity (Wald = 9.57, P = 0.002), with texture nonhomogeneity (hazard ratio (HR) = 1.87 (1.05–3.33), P < 0.05), with calcification size (Wald = 3.11, P < 0.05), but not with parameters of seminal vesicle size or function. In conclusion, in males of infertile couples, MetS is positively associated with prostate enlargement, biochemical (sIL8) and ultrasound-derived signs of prostate inflammation but not with prostate-related symptoms, which suggests that MetS is a trigger for a subclinical, early-onset form of benign prostatic hyperplasia. PMID:24435050

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, K

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 recentmore » 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 CSCs and achieve disease-free, much more fractionations are needed.« less

The expanding role of epigenetics in the development, diagnosis and treatment of prostate cancer and benign prostatic hyperplasia.

PubMed

Dobosy, Joseph R; Roberts, J Lea W; Fu, Vivian X; Jarrard, David F

2007-03-01

Prostate cancer research has focused significant attention on the mutation, deletion or amplification of the DNA base sequence that encodes critical growth or suppressor genes. However, these changes have left significant gaps in our understanding of the development and progression of disease. It has become clear that epigenetic changes or modifications that influence phenotype without altering the genotype present a new and entirely different mechanism for gene regulation. Several interrelated epigenetic modifications that are altered in abnormal growth states are DNA methylation changes, histone modifications and genomic imprinting. We discuss the status of epigenetic alterations in prostate cancer and benign prostatic hyperplasia progression. In addition, the rationale and status of ongoing clinical trials altering epigenetic processes in urological diseases are reviewed. An online search of current and past peer reviewed literature on DNA methylation, histone acetylation and methylation, imprinting and epigenetics in prostate cancer and benign prostatic hyperplasia was performed. Relevant articles and reviews were examined and a synopsis of reproducible data was generated with the goal of informing the practicing urologist of these advances and their implications. Only 20 years ago the first study was published demonstrating global changes in DNA methylation patterns in tumors. Accumulating data have now identified specific genes that are commonly hypermethylated and inactivated during prostate cancer progression, including GSTpi, APC, MDR1, GPX3 and 14-3-3sigma. Altered histone modifications, including acetylation and methylation, were also recently described that may modify gene function, including androgen receptor function. These epigenetic changes are now being used to assist in prostate cancer diagnosis and cancer outcome prediction. Epigenetic changes appear to have a role in benign prostatic hyperplasia development as well as in the susceptibility of the prostate to developing cancer. Treatments involving 5-aza-deoxycytosine and other, more selective DNA methyltransferase inhibitors remove methyl residues from silenced genes, generating re-expression, and are currently being used in therapeutic trials. Histone deacetylase inhibitors have shown promise, not only by directly reactivating silenced genes, but also as regulators of apoptosis and sensitizers to radiation therapy. Evolving data support a significant role for epigenetic processes in the development of prostate cancer and benign prostatic hyperplasia. Epigenetic changes can predict tumor behavior and often distinguish between genetically identical tumors. Targeted drugs that alter epigenetic modifications hold promise as a tool for curing and preventing these diseases.

Etiology of chronic prostatitis syndrome in patients treated at the university hospital for infectious diseases "Dr. Fran Mihaljević" from 2003 to 2005.

PubMed

Skerk, Vianja; Cajić, Vjeran; Markovinović, Leo; Roglić, Srdan; Zekan, Sime; Skerk, Vedrana; Radosević, Velena; Tambić Andragević, Arijana

2006-12-01

A total of 835 patients with symptoms of chronic prostatitis syndrome and no evidence of structural or functional lower genitourinary tract abnormalities were examined in a three year period at the Outpatient Department for Urogenital Infections, University Hospital for Infectious Diseases "Dr. Fran Mihaljević" Zagreb, Croatia. Disease etiology was determined in 482 (57.72%) patients. Chlamydia trachomatis was proved to be the causative pathogen in 161 patients, Trichomonas vaginalis in 85, Escherichia coli in 68, Enterococcus in 51, Proteus mirabilis in 20, Klebsiella pneumoniae in 9, Streptococcus agalactiae in 15, Ureaplasma urealyticum in 49 patients with chronic prostatitis. Other patients had mixed infection. In 257 (53.32%) of 482 patients, the inflammatory finding (>10 WBCs/hpf) was found in EPS or VB3. Normal WBCs/hpf (<10) was found in 103 (63.98%) of 161 patients with symptoms of chronic prostatitis in whom C. trachomatis was detected in EPS or VB3, in 50 (58.82%) of 85 patients in whom Trichomonas vaginalis was isolated, and in 23 (46.94%) of 49 patients in whom Ureaplasma urealyticum was isolated.

Hsp70 and gama-Semino protein as possible prognostic marker of prostate cancer.

PubMed

Kumar, Sanjay; Gurshaney, Sanjeev; Adagunodo, Yori; Gage, Erica; Qadri, Shezreen; Sharma, Mahak; Malik, Shalie; Manne, Upender; Singh, Udai P; Singh, Rajesh; Mishra, Manoj K

2018-06-01

In the United States, Prostate Cancer (PCa) is the leading cause of cancer-related mortality in men. PCa resulted in abnormal growth and function of prostate gland such as secretion of high level of gamma-seminoprotein (gama-SM)/Prostate-Specific Antigen (PSA) which could be detected in the blood. Beside gama-SM protein, the levels of heat shock proteins (Hsp70) were also observed significantly high. Therefore, gama-SM and Hsp70 are unique proteins with high potential for PCa therapeutics and diagnostics. High level of Hsp70 suppresses apoptosis, thus allowing PCa cells to exist; however, depletion of Hsp70 induces apoptosis in PCa cells. Gama-SM is the most prominent biomarker for PCa screening; however, its accuracy is still questionable. Thus, a more suitable streamline biomarker for PCa screening is urgently needed. Hsp70 and gama-SM proteins could be used as a revolutionary biomarker for PCa, and could help to identify possible therapeutic target(s). In this review article we will discuss the relationship between the Hsp70 and gama-SM proteins with PCa, their potential as a dual biomarker, and the possibility for both proteins being used as therapeutic targets.

Regulators of gene expression as biomarkers for prostate cancer

PubMed Central

Willard, Stacey S; Koochekpour, Shahriar

2012-01-01

Recent technological advancements in gene expression analysis have led to the discovery of a promising new group of prostate cancer (PCa) biomarkers that have the potential to influence diagnosis and the prediction of disease severity. The accumulation of deleterious changes in gene expression is a fundamental mechanism of prostate carcinogenesis. Aberrant gene expression can arise from changes in epigenetic regulation or mutation in the genome affecting either key regulatory elements or gene sequences themselves. At the epigenetic level, a myriad of abnormal histone modifications and changes in DNA methylation are found in PCa patients. In addition, many mutations in the genome have been associated with higher PCa risk. Finally, over- or underexpression of key genes involved in cell cycle regulation, apoptosis, cell adhesion and regulation of transcription has been observed. An interesting group of biomarkers are emerging from these studies which may prove more predictive than the standard prostate specific antigen (PSA) serum test. In this review, we discuss recent results in the field of gene expression analysis in PCa including the most promising biomarkers in the areas of epigenetics, genomics and the transcriptome, some of which are currently under investigation as clinical tests for early detection and better prognostic prediction of PCa. PMID:23226612

Quality of radiotherapy reporting in randomized controlled trials of prostate cancer.

PubMed

Soon, Yu Yang; Chen, Desiree; Tan, Teng Hwee; Tey, Jeremy

2018-06-07

Good radiotherapy reporting in clinical trials of prostate radiotherapy is important because it will allow accurate reproducibility of radiotherapy treatment and minimize treatment variations that can affect patient outcomes. The aim of our study is to assess the quality of prostate radiotherapy (RT) treatment reporting in randomized controlled trials in prostate cancer. We searched MEDLINE for randomized trials of prostate cancer, published from 1996 to 2016 and included prostate RT as one of the intervention arms. We assessed if the investigators reported the ten criteria adequately in the trial reports: RT dose prescription method; RT dose-planning procedures; organs at risk (OAR) dose constraints; target volume definition, simulation procedures; treatment verification procedures; total RT dose; fractionation schedule; conduct of quality assurance (QA) as well as presence or absence of deviations in RT treatment planning and delivery. We performed multivariate logistic regression to determine the factors that may influence the quality of reporting. We found 59 eligible trials. There was significant variability in the quality of reporting. Target volume definition, total RT dose and fractionation schedule were reported adequately in 97% of included trials. OAR constraints, simulation procedures and presence or absence of deviations in RT treatment planning and delivery were reported adequately in 30% of included trials. Twenty-four trials (40%) reported seven criteria or more adequately. Multivariable logistic analysis showed that trials that published their quality assurance results and cooperative group trials were more likely to have adequate quality in reporting in at least seven criteria. There is significant variability in the quality of reporting on prostate radiotherapy treatment in randomized trials of prostate cancer. We need to have consensus guidelines to standardize the reporting of radiotherapy treatment in randomized trials.

Investigation of parameters affecting treatment time in MRI-guided transurethral ultrasound therapy

NASA Astrophysics Data System (ADS)

N'Djin, W. A.; Burtnyk, M.; Chopra, R.; Bronskill, M. J.

2010-03-01

MRI-guided transurethral ultrasound therapy shows promise for minimally invasive treatment of localized prostate cancer. Real-time MR temperature feedback enables the 3D control of thermal therapy to define an accurate region within the prostate. Previous in-vivo canine studies showed the feasibility of this method using transurethral planar transducers. The aim of this simulation study was to reduce the procedure time, while maintaining treatment accuracy by investigating new combinations of treatment parameters. A numerical model was used to simulate a multi-element heating applicator rotating inside the urethra in 10 human prostates. Acoustic power and rotation rate were varied based on the feedback of the temperature in the prostate. Several parameters were investigated for improving the treatment time. Maximum acoustic power and rotation rate were optimized interdependently as a function of prostate radius and transducer operating frequency, while avoiding temperatures >90° C in the prostate. Other trials were performed on each parameter separately, with the other parameter fixed. The concept of using dual-frequency transducers was studied, using the fundamental frequency or the 3rd harmonic component depending on the prostate radius. The maximum acoustic power which could be used decreased as a function of the prostate radius and the frequency. Decreasing the frequency (9.7-3.0 MHz) or increasing the power (10-20 W.cm-2) led to treatment times shorter by up to 50% under appropriate conditions. Dual-frequency configurations, while helpful, tended to have less impact on treatment times. Treatment accuracy was maintained and critical adjacent tissues like the rectal wall remained protected. The interdependence between power and frequency may require integrating multi-parametric functions inside the controller for future optimizations. As a first approach, however, even slight modifications of key parameters can be sufficient to reduce treatment time.

Need for and relevance of prostate cancer screening in Nigeria.

PubMed

Akinremi, To; Adeniyi, A; Olutunde, A; Oduniyi, A; Ogo, Cn

2014-01-01

Prostate cancer (PCa) has become the most prevalent cancer among males in Nigeria, and similar to other black populations, Nigerian men present with more advanced disease at an earlier age than in several other ethnic groups. In this unscreened, high-risk group, the reference range for early detection and diagnosis as well as risk factors need to be determined through large-scale screening. Over 4 years, 1124 previously unscreened men between 40 and 85 years of age were screened at free community health programmes for PCa, using the common parameters of prostate-specific antigen (PSA) plus digital rectal examination (DRE). We thereby assessed the practicality and importance of screening. Consent was obtained, demographic data obtained, PSA measured using qualitative laboratory kits, and DRE performed by surgeons. We found that the number of men attending and consenting to screening increases from year to year. Of 40-85-year-old men, 85.4% consented, of whom 33.3% (a third) and 60% were 51-60 years old and 51-65 years, respectively. While 11.5% of men had PSA >4 ng/ml, 31.45% showed abnormal DRE. Of the men who took the PSA test, 79.2% also consented to the DRE, of whom 5.8% had combined abnormal DRE and PSA >4 ng/ml. Our findings suggest that Nigerian men are a willing group for screening by both the PSA and DRE with the positive response to calls for health screening and interest in prostate health. The finding of PSA >4 ng/ml in 11.15% of this population reveals the need for greater awareness and measures to increase early detection. However, the value and validity of established PSA reference ranges and cutoff of 'normal' still need to be established. Screening is very important to better define the PCa prevalence and characteristics in our population; otherwise political and economic circumstances will ensure that men still present late with aggressive PCa.

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.

PubMed

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 < .05). The biopsy findings were positive for PCa in 167 patients (45.1%) and negative in 164 (44.2%). The PCRD index was positively signed in 89.82% positive PCa cases and negative in 91.46% negative PCa cases (χ 2 test; P < .001; relative risk, 8.98). The sensitivity was 89.8%, specificity was 91.5%, positive predictive value was 91.5%, negative predictive value was 89.8%, positive likelihood ratio was 10.5, negative likelihood ratio was 0.11, and accuracy was 90.6%. Multiple logistic 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 accurately calculated the probability of finding cancer on biopsy, on an individual patient basis. Copyright © 2016 Elsevier Inc. All rights reserved.

[Primary malignant lymphoma of the prostate: report of a case achieving complete response to combination chemotherapy and review of 22 Japanese cases].

PubMed

Fukutani, Keiko; Koyama, Yasuhiro; Fujimori, Masahiro; Ishida, Toshimitsu

2003-09-01

A 70-year-old man presented with complaints of difficult urination, perineal pain and lassitude. An enlarged, hard and nodular prostate was palpable on digital rectal examination. Needle biopsy of the prostate was performed, which revealed diffuse large B-cell non-Hodgkin's lymphoma by immunohistochemical studies. Right internal and external iliac nodes were swollen on computed tomographic scan (CT) of the pelvis. No abnormal finding was seen on abdominal CT, upper gastrointestinal fiberscopy and bone marrow histology. Therefore, the disease was classified into the clinical stage II according to Ann Arbor's criteria. The patient achieved complete response (CR) to five cycles of combination chemotherapy, CHOP, and survives more than two years without recurrence. Primary malignant lymphoma of the prostate is a rare prostatic malignancy. Only 22 Japanese cases with primary prostatic lymphoma have been reported to our knowledge. In 23 cases including ours the majority of the patients were older than 60 years, and their histopathology was mostly diffuse lymphoma, which belongs to intermediate grade of non-Hodjkin's lymphoma according to the Working Formulation's Classification. Nineteen out of 23 cases (83%) were divided into localized stage i.e. stage I or II. In these reports, three of five cases treated with either radical prostatectomy or radiotherapy alone resulted in death or progressive disease. On the other hand, 11 out of 16 cases (69%) who received chemotherapy alone or with other therapy obtained CR. Primary lymphoma of prostate has previously been considered to have a poor prognosis. Our results, however, suggest that patients with this malignancy respond well to combined chemotherapy, and could possibly be cured when the disease is confined to the localized stage.

Serum PSA levels in the Indian population: Is it different?

PubMed

Agrawal, Amit; Karan, Shailesh Chandra

2017-04-01

Serum prostate-specific antigen (PSA) is an important tumour, marker which is widely used to trigger trans-rectal ultrasound (TRUS)-guided prostate biopsy. However, the PSA levels vary with race and ethnicity. Therefore, there is a need to have an Indian reference range. All adult male patients meeting the inclusion and exclusion criteria were enrolled in this study. They were subjected to assessment of serum total PSA, digital rectal examination and trans-abdominal ultrasound. If any one or more of these were found abnormal, then a TRUS-guided 12-core prostate biopsy was done. Patients who were detected to have prostatic cancer were excluded from the final analysis. The data so obtained was grouped among the following three age groups: 40-49, 50-59 and 60-70 years, and the age-specific PSA values, prostatic volume and PSA density were found. A total of 1772 patients were analysed. The mean serum total PSA was 1.76 ng/ml with a standard deviation of 2.566 ng/ml. Group-wise age distribution of the mean serum total PSA was 1.22, 1.97 and 2.08 ng/ml in 40-49, 50-59 and 60-70 years age groups. The mean total PSA and the age-specific PSA range tend to be lower in the Indians than the Western population.

Prostate cancer detection using machine learning techniques by employing combination of features extracting strategies.

PubMed

Hussain, Lal; Ahmed, Adeel; Saeed, Sharjil; Rathore, Saima; Awan, Imtiaz Ahmed; Shah, Saeed Arif; Majid, Abdul; Idris, Adnan; Awan, Anees Ahmed

2018-02-06

Prostate is a second leading causes of cancer deaths among men. Early detection of cancer can effectively reduce the rate of mortality caused by Prostate cancer. Due to high and multiresolution of MRIs from prostate cancer require a proper diagnostic systems and tools. In the past researchers developed Computer aided diagnosis (CAD) systems that help the radiologist to detect the abnormalities. In this research paper, we have employed novel Machine learning techniques such as Bayesian approach, Support vector machine (SVM) kernels: polynomial, radial base function (RBF) and Gaussian and Decision Tree for detecting prostate cancer. Moreover, different features extracting strategies are proposed to improve the detection performance. The features extracting strategies are based on texture, morphological, scale invariant feature transform (SIFT), and elliptic Fourier descriptors (EFDs) features. The performance was evaluated based on single as well as combination of features using Machine Learning Classification techniques. The Cross validation (Jack-knife k-fold) was performed and performance was evaluated in term of receiver operating curve (ROC) and specificity, sensitivity, Positive predictive value (PPV), negative predictive value (NPV), false positive rate (FPR). Based on single features extracting strategies, SVM Gaussian Kernel gives the highest accuracy of 98.34% with AUC of 0.999. While, using combination of features extracting strategies, SVM Gaussian kernel with texture + morphological, and EFDs + morphological features give the highest accuracy of 99.71% and AUC of 1.00.

SU-G-BRA-17: Tracking Multiple Targets with Independent Motion in Real-Time Using a Multi-Leaf Collimator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ge, Y; Keall, P; Poulsen, P

Purpose: Multiple targets with large intrafraction independent motion are often involved in advanced prostate, lung, abdominal, and head and neck cancer radiotherapy. Current standard of care treats these with the originally planned fields, jeopardizing the treatment outcomes. A real-time multi-leaf collimator (MLC) tracking method has been developed to address this problem for the first time. This study evaluates the geometric uncertainty of the multi-target tracking method. Methods: Four treatment scenarios are simulated based on a prostate IMAT plan to treat a moving prostate target and static pelvic node target: 1) real-time multi-target MLC tracking; 2) real-time prostate-only MLC tracking; 3)more » correcting for prostate interfraction motion at setup only; and 4) no motion correction. The geometric uncertainty of the treatment is assessed by the sum of the erroneously underexposed target area and overexposed healthy tissue areas for each individual target. Two patient-measured prostate trajectories of average 2 and 5 mm motion magnitude are used for simulations. Results: Real-time multi-target tracking accumulates the least uncertainty overall. As expected, it covers the static nodes similarly well as no motion correction treatment and covers the moving prostate similarly well as the real-time prostate-only tracking. Multi-target tracking reduces >90% of uncertainty for the static nodal target compared to the real-time prostate-only tracking or interfraction motion correction. For prostate target, depending on the motion trajectory which affects the uncertainty due to leaf-fitting, multi-target tracking may or may not perform better than correcting for interfraction prostate motion by shifting patient at setup, but it reduces ∼50% of uncertainty compared to no motion correction. Conclusion: The developed real-time multi-target MLC tracking can adapt for the independently moving targets better than other available treatment adaptations. This will enable PTV margin reduction to minimize health tissue toxicity while remain tumor coverage when treating advanced disease with independently moving targets involved. The authors acknowledge funding support from the Australian NHMRC Australia Fellowship and NHMRC Project Grant No. APP1042375.« less

Intratumor DNA methylation heterogeneity reflects clonal evolution in aggressive prostate cancer.

PubMed

Brocks, David; Assenov, Yassen; Minner, Sarah; Bogatyrova, Olga; Simon, Ronald; Koop, Christina; Oakes, Christopher; Zucknick, Manuela; Lipka, Daniel Bernhard; Weischenfeldt, Joachim; Feuerbach, Lars; Cowper-Sal Lari, Richard; Lupien, Mathieu; Brors, Benedikt; Korbel, Jan; Schlomm, Thorsten; Tanay, Amos; Sauter, Guido; Gerhäuser, Clarissa; Plass, Christoph

2014-08-07

Despite much evidence on epigenetic abnormalities in cancer, it is currently unclear to what extent epigenetic alterations can be associated with tumors' clonal genetic origins. Here, we show that the prostate intratumor heterogeneity in DNA methylation and copy-number patterns can be explained by a unified evolutionary process. By assaying multiple topographically distinct tumor sites, premalignant lesions, and lymph node metastases within five cases of prostate cancer, we demonstrate that both DNA methylation and copy-number heterogeneity consistently reflect the life history of the tumors. Furthermore, we show cases of genetic or epigenetic convergent evolution and highlight the diversity in the evolutionary origins and aberration spectrum between tumor and metastatic subclones. Importantly, DNA methylation can complement genetic data by serving as a proxy for activity at regulatory domains, as we show through identification of high epigenetic heterogeneity at androgen-receptor-bound enhancers. Epigenome variation thereby expands on the current genome-centric view on tumor heterogeneity. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

A statistical motion model based on biomechanical simulations for data fusion during image-guided prostate interventions.

PubMed

Hu, Yipeng; Morgan, Dominic; Ahmed, Hashim Uddin; Pendsé, Doug; Sahu, Mahua; Allen, Clare; Emberton, Mark; Hawkes, David; Barratt, Dean

2008-01-01

A method is described for generating a patient-specific, statistical motion model (SMM) of the prostate gland. Finite element analysis (FEA) is used to simulate the motion of the gland using an ultrasound-based 3D FE model over a range of plausible boundary conditions and soft-tissue properties. By applying principal component analysis to the displacements of the FE mesh node points inside the gland, the simulated deformations are then used as training data to construct the SMM. The SMM is used to both predict the displacement field over the whole gland and constrain a deformable surface registration algorithm, given only a small number of target points on the surface of the deformed gland. Using 3D transrectal ultrasound images of the prostates of five patients, acquired before and after imposing a physical deformation, to evaluate the accuracy of predicted landmark displacements, the mean target registration error was found to be less than 1.9 mm.

Epigenetic Transgenerational Actions of Vinclozolin on the Development of Disease and Cancer

PubMed Central

Skinner, Michael K.; Anway, Matthew D.

2018-01-01

Exposure to an environmental endocrine disruptor (e.g., vinclozolin) during embryonic gonadal sex determination appears to alter the male germ line epigenome and subsequently promotes transgenerational adult onset disease. The epigenetic mechanism involves the induction of new imprinted-like genes/DNA sequences in the germ line that appear to transmit disease phenotypes. The disease phenotypes include testis abnormalities, prostate disease, kidney disease, immune abnormalities, and tumor development. This epigenetic transgenerational disease mechanism provides a unique perspective from which to view inheritable adult onset disease states, such as cancer, and ultimately offers new insights into novel diagnostic and therapeutic strategies. PMID:17956218

The fractionated dipole antenna: A new antenna for body imaging at 7 Tesla.

PubMed

Raaijmakers, Alexander J E; Italiaander, Michel; Voogt, Ingmar J; Luijten, Peter R; Hoogduin, Johannes M; Klomp, Dennis W J; van den Berg, Cornelis A T

2016-03-01

Dipole antennas in ultrahigh field MRI have demonstrated advantages over more conventional designs. In this study, the fractionated dipole antenna is presented: a dipole where the legs are split into segments that are interconnected by capacitors or inductors. A parameter study has been performed on dipole antenna length using numerical simulations. A subsequent simulation study investigates the optimal intersegment capacitor/inductor value. The resulting optimal design has been constructed and compared to a previous design, the single-side adapted dipole (SSAD) by simulations and measurements. An array of eight elements has been constructed for prostate imaging on four subjects (body mass index 20-27.5) using 8 × 2 kW amplifiers. For prostate imaging at 7T, lowest peak local specific-absorption rate (SAR) levels are achieved if the antenna is 30 cm or longer. A fractionated dipole antenna design with inductors between segments has been chosen to achieve even lower SAR levels and more homogeneous receive sensitivities. With the new design, good quality prostate images are acquired. SAR levels are reduced by 41% to 63% in comparison to the SSAD. Coupling levels are moderate (average nearest neighbor: -14.6 dB) for each subject and prostate B1+ levels range from 12 to 18 μT. © 2015 Wiley Periodicals, Inc.

Fused-data transrectal EIT for prostate cancer imaging.

PubMed

Murphy, Ethan K; Wu, Xiaotian; Halter, Ryan J

2018-05-25

Prostate cancer is a significant problem affecting 1 in 7 men. Unfortunately, the diagnostic gold-standard of ultrasound-guided biopsy misses 10%-30% of all cancers. The objective of this study was to develop an electrical impedance tomography (EIT) approach that has the potential to image the entire prostate using multiple impedance measurements recorded between electrodes integrated onto an end-fired transrectal ultrasound (TRUS) device and a biopsy probe (BP). Simulations and sensitivity analyses were used to investigate the best combination of electrodes, and measured tank experiments were used to evaluate a fused-data transrectal EIT (fd-TREIT) and BP approach. Simulations and sensitivity analysis revealed that (1) TREIT measurements are not sufficiently sensitive to image the whole prostate, (2) the combination of TREIT  +  BP measurements increases the sensitive region of TREIT-only measurements by 12×, and (3) the fusion of multiple TREIT  +  BP measurements collected during a routine or customized 12-core biopsy procedure can cover up to 76.1% or 94.1% of a nominal 50 cm 3 prostate, respectively. Three measured tank experiments of the fd-TREIT  +  BP approach successfully and accurately recovered the positions of 2-3 metal or plastic inclusions. The measured tank experiments represent important steps in the development of an algorithm that can combine EIT from multiple locations and from multiple probes-data that could be collected during a routine TRUS-guided 12-core biopsy. Overall, this result is a step towards a clinically deployable impedance imaging approach to scanning the entire prostate, which could significantly help to improve prostate cancer diagnosis.

Prostate-cancer diagnosis by non-invasive prostatic Zinc mapping using X-Ray Fluorescence (XRF)

NASA Astrophysics Data System (ADS)

Cortesi, Marco

At present, the major screening tools (PSA, DRE, TRUS) for prostate cancer lack sensitivity and specificity, and none can distinguish between low-grade indolent cancer and high-grade lethal one. The situation calls for the promotion of alternative approaches, with better detection sensitivity and specificity, to provide more efficient selection of patients to biopsy and with possible guidance of the biopsy needles. The prime objective of the present work was the development of a novel non-invasive method and tool for promoting detection, localization, diagnosis and follow-up of PCa. The method is based on in-vivo imaging of Zn distribution in the peripheral zone of the prostate, by a trans-rectal X-ray fluorescence (XRF) probe. Local Zn levels, measured in 1--4 mm3 fresh tissue biopsy segments from an extensive clinical study involving several hundred patients, showed an unambiguous correlation with the histological classification of the tissue (Non-Cancer or PCa), and a systematic positive correlation of its depletion level with the cancer-aggressiveness grade (Gleason classification). A detailed analysis of computer-simulated Zn-concentration images (with input parameters from clinical data) disclosed the potential of the method to provide sensitive and specific detection and localization of the lesion, its grade and extension. Furthermore, it also yielded invaluable data on some requirements, such as the image resolution and counting-statistics, requested from a trans-rectal XRF probe for in-vivo recording of prostatic-Zn maps in patients. By means of systematic table-top experiments on prostate-phantoms comprising tumor-like inclusions, followed by dedicated Monte Carlo simulations, the XRF-probe and its components have been designed and optimized. Multi-parameter analysis of the experimental data confirmed the simulation estimations of the XRF detection system in terms of: delivered dose, counting statistics, scanning resolution, target-volume size and the accuracy of locating at various depths of small-volume tumor-like inclusions in tissue-phantoms. The clinical study, the Monte Carlo simulations and the analysis of Zn-map images provided essential information and promising vision on the potential performance of the Zn-based PCa detection concept. Simulations focusing on medical-probe design and its performance at permissible radiation doses yielded positive results - confirmed by a series of systematic laboratory experiments with a table-top XRF system.

Dynamic Collimator Angle Adjustments During Volumetric Modulated Arc Therapy to Account for Prostate Rotations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boer, Johan de; Wolf, Anne Lisa; Szeto, Yenny Z.

2015-04-01

Purpose: Rotations of the prostate gland induce considerable geometric uncertainties in prostate cancer radiation therapy. Collimator and gantry angle adjustments can correct these rotations in intensity modulated radiation therapy. Modern volumetric modulated arc therapy (VMAT) treatments, however, include a wide range of beam orientations that differ in modulation, and corrections require dynamic collimator rotations. The aim of this study was to implement a rotation correction strategy for VMAT dose delivery and validate it for left-right prostate rotations. Methods and Materials: Clinical VMAT treatment plans of 5 prostate cancer patients were used. Simulated left-right prostate rotations between +15° and −15° weremore » corrected by collimator rotations. We compared corrected and uncorrected plans by dose volume histograms, minimum dose (D{sub min}) to the prostate, bladder surface receiving ≥78 Gy (S78) and rectum equivalent uniform dose (EUD; n=0.13). Each corrected plan was delivered to a phantom, and its deliverability was evaluated by γ-evaluation between planned and delivered dose, which was reconstructed from portal images acquired during delivery. Results: On average, clinical target volume minimum dose (D{sub min}) decreased up to 10% without corrections. Negative left-right rotations were corrected almost perfectly, whereas D{sub min} remained within 4% for positive rotations. Bladder S78 and rectum EUD of the corrected plans matched those of the original plans. The average pass rate for the corrected plans delivered to the phantom was 98.9% at 3% per 3 mm gamma criteria. The measured dose in the planning target volume approximated the original dose, rotated around the simulated left-right angle, well. Conclusions: It is feasible to dynamically adjust the collimator angle during VMAT treatment delivery to correct for prostate rotations. This technique can safely correct for left-right prostate rotations up to 15°.« less

PKCε Is an Essential Mediator of Prostate Cancer Bone Metastasis.

PubMed

Gutierrez-Uzquiza, Alvaro; Lopez-Haber, Cynthia; Jernigan, Danielle L; Fatatis, Alessandro; Kazanietz, Marcelo G

2015-09-01

The bone is a preferred site for metastatic homing of prostate cancer cells. Once prostate cancer patients develop skeletal metastases, they eventually succumb to the disease; therefore, it is imperative to identify key molecular drivers of this process. This study examines the involvement of protein kinase C epsilon (PKCε), an oncogenic protein that is abnormally overexpressed in human tumor specimens and cell lines, on prostate cancer cell bone metastasis. PC3-ML cells, a highly invasive prostate cancer PC3 derivative with bone metastatic colonization properties, failed to induce skeletal metastatic foci upon inoculation into nude mice when PKCε expression was silenced using shRNA. Interestingly, while PKCε depletion had only marginal effects on the proliferative, adhesive, and migratory capacities of PC3-ML cells in vitro or in the growth of xenografts upon s.c. inoculation, it caused a significant reduction in cell invasiveness. Notably, PKCε was required for transendothelial cell migration (TEM) as well as for the growth of PC3-ML cells in a bone biomimetic environment. At a mechanistic level, PKCε depletion abrogates the expression of IL1β, a cytokine implicated in skeletal metastasis. Taken together, PKCε is a key factor for driving the formation of bone metastasis by prostate cancer cells and is a potential therapeutic target for advanced stages of the disease. This study uncovers an important new function of PKCε in the dissemination of cancer cells to the bone; thus, highlighting the promising potential of this oncogenic kinase as a therapeutic target for skeletal metastasis. ©2015 American Association for Cancer Research.

EFEMP1 as a novel DNA methylation marker for prostate cancer: array-based DNA methylation and expression profiling.

PubMed

Kim, Yong-June; Yoon, Hyung-Yoon; Kim, Seon-Kyu; Kim, Young-Won; Kim, Eun-Jung; Kim, Isaac Yi; Kim, Wun-Jae

2011-07-01

Abnormal DNA methylation is associated with many human cancers. The aim of the present study was to identify novel methylation markers in prostate cancer (PCa) by microarray analysis and to test whether these markers could discriminate normal and PCa cells. Microarray-based DNA methylation and gene expression profiling was carried out using a panel of PCa cell lines and a control normal prostate cell line. The methylation status of candidate genes in prostate cell lines was confirmed by real-time reverse transcriptase-PCR, bisulfite sequencing analysis, and treatment with a demethylation agent. DNA methylation and gene expression analysis in 203 human prostate specimens, including 106 PCa and 97 benign prostate hyperplasia (BPH), were carried out. Further validation using microarray gene expression data from the Gene Expression Omnibus (GEO) was carried out. Epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) was identified as a lead candidate methylation marker for PCa. The gene expression level of EFEMP1 was significantly higher in tissue samples from patients with BPH than in those with PCa (P < 0.001). The sensitivity and specificity of EFEMP1 methylation status in discriminating between PCa and BPH reached 95.3% (101 of 106) and 86.6% (84 of 97), respectively. From the GEO data set, we confirmed that the expression level of EFEMP1 was significantly different between PCa and BPH. Genome-wide characterization of DNA methylation profiles enabled the identification of EFEMP1 aberrant methylation patterns in PCa. EFEMP1 might be a useful indicator for the detection of PCa.

Prostate Cancer Metastases Alter Bone Mineral and Matrix Composition Independent of Effects on Bone Architecture in Mice A Quantitative Study Using microCT and Raman Spectroscopy

PubMed Central

Bi, Xiaohong; Sterling, Julie A.; Merkel, Alyssa R.; Perrien, Daniel S.; Nyman, Jeffry; Mahadevan-Jansen, Anita

2013-01-01

Prostate cancer is the most common primary tumor and the second leading cause of cancer-related deaths in men in the United States. Prostate cancer bone metastases are characterized by abnormal bone remodeling processes and result in a variety of skeletal morbidities. Prevention of skeletal complications is a crucial element in prostate cancer management. This study investigated prostate cancer-induced alterations in the molecular composition and morphological structure of metastasis-bearing bones in a mouse model of prostate cancer using Raman spectroscopy and micro-computed tomography (microCT). LNCaP C4-2B prostate cancer cells were injected into the right tibiae of 5-week old male SCID mice. Upon sacrifice at 8 weeks post tumor inoculation, two out of the ten tumor-bearing tibiae showed only osteoblastic lesions in the radiographs, 4 osteolytic lesions only and 4 mixed with osteoblastic and osteolytic lesions.. Carbonate substitution was significantly increased while there was a marked reduction in the level of collagen mineralization, mineral crystallinity, and carbonate:matrix ratio in the cortex of the intact tumor-bearing tibiae compared to contralateral controls. MicroCT analysis revealed a significant reduction in bone volume/total volume, trabecular number and trabecular thickness, as well as significant increase in bone surface/volume ratio in tibiae with osteolytic lesions, suggesting active bone remodeling and bone loss. None of the changes in bone compositional properties were correlated with lesion area from radiographs or the changes in bone architecture from microCT. This study indicates that LNCaP C4-2B prostate cancer metastases alter bone tissue composition independent of changes in architecture, and altered bone quality may be an important contributor to fracture risk in these patients. Raman spectroscopy may provide a new avenue of investigation into interactions between tumor and bone microenvironment. PMID:23867219

PCA3-based nomogram for predicting prostate cancer and high grade cancer on initial transrectal guided biopsy.

PubMed

Elshafei, Ahmed; Chevli, K Kent; Moussa, Ayman S; Kara, Onder; Chueh, Shih-Chieh; Walter, Peter; Hatem, Asmaa; Gao, Tianming; Jones, J Stephen; Duff, Michael

2015-12-01

To develop a validated prostate cancer antigen 3 (PCA3) based nomogram that predicts likelihood of overall prostate cancer (PCa) and intermediate/high grade prostate cancer (HGPCa) in men pursuing initial transrectal prostate biopsy (TRUS-PBx). Data were collected on 3,675 men with serum prostate specific antigen level (PSA) ≤ 20 ng/ml who underwent initial prostate biopsy with at least 10 cores sampling at time of the biopsy. Two logistic regression models were constructed to predict overall PCa and HGPCa incorporating age, race, family history (FH) of PCa, PSA at diagnosis, PCA3, total prostate volume (TPV), and digital rectal exam (DRE). One thousand six hundred twenty (44%) patients had biopsy confirmed PCa with 701 men (19.1%) showing HGPCa. Statistically significant predictors of overall PCa were age (P < 0.0001, OR. 1.51), PSA at diagnosis (P < 0.0001, OR.1.95), PCA3 (P < 0.0001, OR.3.06), TPV (P < 0.0001, OR.0.47), FH (P = 0.003, OR.1.32), and abnormal DRE (P = 0.001, OR. 1.32). While for HGPCa, predictors were age (P < 0.0001, OR.1.77), PSA (P < 0.0001, OR.2.73), PCA3 (P < 0.0001, OR.2.26), TPV (P < 0.0001, OR.0.4), and DRE (P < 0.0001, OR.1.53). Two nomograms were reconstructed for predicted overall PCa probability at time of initial biopsy with a concordance index of 0.742 (Fig. 1), and HGPCa with a concordance index of 0.768 (Fig. 2). Our internally validated initial biopsy PCA3 based nomogram is reconstructed based on a large dataset. The c-index indicates high predictive accuracy, especially for high grade PCa and improves the ability to predict biopsy outcomes. © 2015 Wiley Periodicals, Inc.

Dose Volume Histogram (DVH) Analysis in Intensity Modulation Radiation Therapy (IMRT) Treatments for Prostate Cancers

NASA Astrophysics Data System (ADS)

Pyakuryal, Anil

2009-05-01

Studies have shown that as many as 8 out of 10 men had prostate cancer by age 80.Prostate cancer begins with small changes (prostatic intraepithelial neoplasia(PIN)) in size and shape of prostate gland cells,known as prostate adenocarcinoma.With advent in technology, prostate cancer has been the most widely used application of IMRT with the longest follow-up periods.Prostate cancer fits the ideal target criteria for IMRT of adjacent sensitive dose-limiting tissue (rectal, bladder).A retrospective study was performed on 10 prostate cancer patients treated with radiation to a limited pelvic field with a standard 4 field arrangements at dose 45 Gy, and an IMRT boost field to a total isocenter dose of 75 Gy.Plans were simulated for 4 field and the supplementary IMRT treatments with proposed dose delivery at 1.5 Gy/fraction in BID basis.An automated DVH analysis software, HART (S. Jang et al., 2008,Med Phys 35,p.2812)was used to perform DVH assessments in IMRT plans.A statistical analysis of dose coverage at targets in prostate gland and neighboring critical organs,and the plan indices(homogeneity, conformality etc) evaluations were also performed using HART extracted DVH statistics.Analyzed results showed a better correlation with the proposed outcomes (TCP, NTCP) of the treatments.

Shape-based reconstruction for transrectal diffuse optical tomography monitoring of photothermal focal therapy of prostate cancer: simulation studies

NASA Astrophysics Data System (ADS)

Weersink, Robert A.; Chaudhary, Sahil; Mayo, Kenwrick; He, Jie; Wilson, Brian C.

2017-04-01

We develop and demonstrate a simple shape-based approach for diffuse optical tomographic reconstruction of coagulative lesions generated during interstitial photothermal therapy (PTT) of the prostate. The shape-based reconstruction assumes a simple ellipsoid shape, matching the general dimensions of a cylindrical diffusing fiber used for light delivery in current clinical studies of PTT in focal prostate cancer. The specific requirement is to accurately define the border between the photothermal lesion and native tissue as the photothermal lesion grows, with an accuracy of ≤1 mm, so treatment can be terminated before there is damage to the rectal wall. To demonstrate the feasibility of the shape-based diffuse optical tomography reconstruction, simulated data were generated based on forward calculations in known geometries that include the prostate, rectum, and lesions of varying dimensions. The only source of optical contrast between the lesion and prostate was increased scattering in the lesion, as is typically observed with coagulation. With noise added to these forward calculations, lesion dimensions were reconstructed using the shape-based method. This approach for reconstruction is shown to be feasible and sufficiently accurate for lesions that are within 4 mm from the rectal wall. The method was also robust for irregularly shaped lesions.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zoberi, J.

Brachytherapy has proven to be an effective treatment option for prostate cancer. Initially, prostate brachytherapy was delivered through permanently implanted low dose rate (LDR) radioactive sources; however, high dose rate (HDR) temporary brachytherapy for prostate cancer is gaining popularity. Needle insertion during prostate brachytherapy is most commonly performed under ultrasound (U/S) guidance; however, treatment planning may be performed utilizing several imaging modalities either in an intra- or post-operative setting. During intra-operative prostate HDR, the needles are imaged during implantation, and planning may be performed in real time. At present, the most common imaging modality utilized for intra-operative prostate HDR ismore » U/S. Alternatively, in the post-operative setting, following needle implantation, patients may be simulated with computed tomography (CT) or magnetic resonance imaging (MRI). Each imaging modality and workflow provides its share of benefits and limitations. Prostate HDR has been adopted in a number of cancer centers across the nation. In this educational session, we will explore the role of U/S, CT, and MRI in HDR prostate brachytherapy. Example workflows and operational details will be shared, and we will discuss how to establish a prostate HDR program in a clinical setting. Learning Objectives: Review prostate HDR techniques based on the imaging modality Discuss the challenges and pitfalls introduced by the three imagebased options for prostate HDR brachytherapy Review the QA process and learn about the development of clinical workflows for these imaging options at different institutions.« less

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

PubMed

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.

Effect of intrafractional prostate motion on simultaneous boost intensity-modulated radiotherapy to the prostate: A simulation study based on intrafractional motion in the prone position

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ikeda, Itaru; Mizowaki, Takashi, E-mail: mizo@kuhp.kyoto-u.ac.jp; Ono, Tomohiro

2015-01-01

Although the prostate displacement of patients in the prone position is affected by respiration-induced motion, the effect of intrafractional prostate motion in the prone position during “simultaneous integrated boost intensity-modulated radiotherapy” (SIB-IMRT) is unclear. The purpose of this study was to evaluate the dosimetric effects of intrafractional motion on SIB-IMRT to a dominant intraprostatic lesion (IPL) using measured motion data of patients in a prone position, fixed with a thermoplastic shell. We obtained 2 orthogonal x-ray fluoroscopic images at the same moment every 0.2 seconds for 30 seconds before and after treatment, once weekly, from 7 patients with localized prostatemore » cancer with detectable prostatic calcification. Prostate displacements in the left-right (LR), anteroposterior (AP), and superoinferior (SI) directions were calculated using the prostatic calcification as a fiducial marker. We defined the displacement between pretreatment and posttreatment as baseline drift (BD). An SIB-IMRT plan was generated in which each IPL + 3 mm received a dose of 94.5 Gy, whereas the remainder of the prostate + 7 mm received a dose of 75.6 Gy in 9 fields. A simulated plan of dose blurring was generated by the convolution of isocenter-shifted plans using measured motion data in 30 seconds and motion in 30 seconds + distance between pretreatment and posttreatment position (BD) for each of the 7 patients. The motion in 30 seconds mainly reflected respiration-induced motion. The mean displacements of BD were 1.4 mm (− 3.1 to 8.2 mm), − 2.2 mm (− 9.1 to 1.5 mm), and − 0.3 mm (− 5.0 to 1.8 mm) in the AP, SI, and LR directions, respectively. The differences in the target coverage with V{sub 90%} of the IPL and V{sub 100%} of the prostate between the simulated plan and original plan were − 3.9% to − 0.3% and − 0.6% to 1.1% for respiration-induced motion and 3.1% to − 67.8% and 3.6% to − 13.3% for BD with respiration-induced motion, respectively. The large motion of BD resulted in an inadequate coverage by the prescribed dose of the SIB-IMRT to the IPL. A 7-mm margin is recommended when real-time tracking techniques are not applied. The effect of respiration-induced motion was small, so long as a 3-mm margin was added.« less

DMLC tracking and gating can improve dose coverage for prostate VMAT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Colvill, E.; Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, NSW 2065; School of Physics, University of Sydney, NSW 2006

2014-09-15

Purpose: To assess and compare the dosimetric impact of dynamic multileaf collimator (DMLC) tracking and gating as motion correction strategies to account for intrafraction motion during conventionally fractionated prostate radiotherapy. Methods: A dose reconstruction method was used to retrospectively assess the dose distributions delivered without motion correction during volumetric modulated arc therapy fractions for 20 fractions of five prostate cancer patients who received conventionally fractionated radiotherapy. These delivered dose distributions were compared with the dose distributions which would have been delivered had DMLC tracking or gating motion correction strategies been implemented. The delivered dose distributions were constructed by incorporating themore » observed prostate motion with the patient's original treatment plan to simulate the treatment delivery. The DMLC tracking dose distributions were constructed using the same dose reconstruction method with the addition of MLC positions from Linac log files obtained during DMLC tracking simulations with the observed prostate motions input to the DMLC tracking software. The gating dose distributions were constructed by altering the prostate motion to simulate the application of a gating threshold of 3 mm for 5 s. Results: The delivered dose distributions showed that dosimetric effects of intrafraction prostate motion could be substantial for some fractions, with an estimated dose decrease of more than 19% and 34% from the planned CTVD{sub 99%} and PTV D{sub 95%} values, respectively, for one fraction. Evaluation of dose distributions for DMLC tracking and gating deliveries showed that both interventions were effective in improving the CTV D{sub 99%} for all of the selected fractions to within 4% of planned value for all fractions. For the delivered dose distributions the difference in rectum V{sub 65%} for the individual fractions from planned ranged from −44% to 101% and for the bladder V{sub 65%} the range was −61% to 26% from planned. The application of tracking decreased the maximum rectum and bladder V{sub 65%} difference to 6% and 4%, respectively. Conclusions: For the first time, the dosimetric impact of DMLC tracking and gating to account for intrafraction motion during prostate radiotherapy has been assessed and compared with no motion correction. Without motion correction intrafraction prostate motion can result in a significant decrease in target dose coverage for a small number of individual fractions. This is unlikely to effect the overall treatment for most patients undergoing conventionally fractionated treatments. Both DMLC tracking and gating demonstrate dose distributions for all assessed fractions that are robust to intrafraction motion.« less

MO-B-BRC-04: MRI-Based Prostate HDR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mourtada, F.

2016-06-15

Brachytherapy has proven to be an effective treatment option for prostate cancer. Initially, prostate brachytherapy was delivered through permanently implanted low dose rate (LDR) radioactive sources; however, high dose rate (HDR) temporary brachytherapy for prostate cancer is gaining popularity. Needle insertion during prostate brachytherapy is most commonly performed under ultrasound (U/S) guidance; however, treatment planning may be performed utilizing several imaging modalities either in an intra- or post-operative setting. During intra-operative prostate HDR, the needles are imaged during implantation, and planning may be performed in real time. At present, the most common imaging modality utilized for intra-operative prostate HDR ismore » U/S. Alternatively, in the post-operative setting, following needle implantation, patients may be simulated with computed tomography (CT) or magnetic resonance imaging (MRI). Each imaging modality and workflow provides its share of benefits and limitations. Prostate HDR has been adopted in a number of cancer centers across the nation. In this educational session, we will explore the role of U/S, CT, and MRI in HDR prostate brachytherapy. Example workflows and operational details will be shared, and we will discuss how to establish a prostate HDR program in a clinical setting. Learning Objectives: Review prostate HDR techniques based on the imaging modality Discuss the challenges and pitfalls introduced by the three imagebased options for prostate HDR brachytherapy Review the QA process and learn about the development of clinical workflows for these imaging options at different institutions.« less

MO-B-BRC-00: Prostate HDR Treatment Planning - Considering Different Imaging Modalities

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2016-06-15

Brachytherapy has proven to be an effective treatment option for prostate cancer. Initially, prostate brachytherapy was delivered through permanently implanted low dose rate (LDR) radioactive sources; however, high dose rate (HDR) temporary brachytherapy for prostate cancer is gaining popularity. Needle insertion during prostate brachytherapy is most commonly performed under ultrasound (U/S) guidance; however, treatment planning may be performed utilizing several imaging modalities either in an intra- or post-operative setting. During intra-operative prostate HDR, the needles are imaged during implantation, and planning may be performed in real time. At present, the most common imaging modality utilized for intra-operative prostate HDR ismore » U/S. Alternatively, in the post-operative setting, following needle implantation, patients may be simulated with computed tomography (CT) or magnetic resonance imaging (MRI). Each imaging modality and workflow provides its share of benefits and limitations. Prostate HDR has been adopted in a number of cancer centers across the nation. In this educational session, we will explore the role of U/S, CT, and MRI in HDR prostate brachytherapy. Example workflows and operational details will be shared, and we will discuss how to establish a prostate HDR program in a clinical setting. Learning Objectives: Review prostate HDR techniques based on the imaging modality Discuss the challenges and pitfalls introduced by the three imagebased options for prostate HDR brachytherapy Review the QA process and learn about the development of clinical workflows for these imaging options at different institutions.« less

MO-B-BRC-02: Ultrasound Based Prostate HDR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Z.

2016-06-15

Brachytherapy has proven to be an effective treatment option for prostate cancer. Initially, prostate brachytherapy was delivered through permanently implanted low dose rate (LDR) radioactive sources; however, high dose rate (HDR) temporary brachytherapy for prostate cancer is gaining popularity. Needle insertion during prostate brachytherapy is most commonly performed under ultrasound (U/S) guidance; however, treatment planning may be performed utilizing several imaging modalities either in an intra- or post-operative setting. During intra-operative prostate HDR, the needles are imaged during implantation, and planning may be performed in real time. At present, the most common imaging modality utilized for intra-operative prostate HDR ismore » U/S. Alternatively, in the post-operative setting, following needle implantation, patients may be simulated with computed tomography (CT) or magnetic resonance imaging (MRI). Each imaging modality and workflow provides its share of benefits and limitations. Prostate HDR has been adopted in a number of cancer centers across the nation. In this educational session, we will explore the role of U/S, CT, and MRI in HDR prostate brachytherapy. Example workflows and operational details will be shared, and we will discuss how to establish a prostate HDR program in a clinical setting. Learning Objectives: Review prostate HDR techniques based on the imaging modality Discuss the challenges and pitfalls introduced by the three imagebased options for prostate HDR brachytherapy Review the QA process and learn about the development of clinical workflows for these imaging options at different institutions.« less

A novel adaptive needle insertion sequencing for robotic, single needle MR-guided high-dose-rate prostate brachytherapy

NASA Astrophysics Data System (ADS)

Borot de Battisti, M.; de Senneville, B. Denis; Hautvast, G.; Binnekamp, D.; Lagendijk, J. J. W.; Maenhout, M.; Moerland, M. A.

2017-05-01

MR-guided high-dose-rate (HDR) brachytherapy has gained increasing interest as a treatment for patients with localized prostate cancer because of the superior value of MRI for tumor and surrounding tissues localization. To enable needle insertion into the prostate with the patient in the MR bore, a single needle MR-compatible robotic system involving needle-by-needle dose delivery has been developed at our institution. Throughout the intervention, dose delivery may be impaired by: (1) sub-optimal needle positioning caused by e.g. needle bending, (2) intra-operative internal organ motion such as prostate rotations or swelling, or intra-procedural rectum or bladder filling. This may result in failure to reach clinical constraints. To assess the first aforementioned challenge, a recent study from our research group demonstrated that the deposited dose may be greatly improved by real-time adaptive planning with feedback on the actual needle positioning. However, the needle insertion sequence is left to the doctor and therefore, this may result in sub-optimal dose delivery. In this manuscript, a new method is proposed to determine and update automatically the needle insertion sequence. This strategy is based on the determination of the most sensitive needle track. The sensitivity of a needle track is defined as its impact on the dose distribution in case of sub-optimal positioning. A stochastic criterion is thus presented to determine each needle track sensitivity based on needle insertion simulations. To assess the proposed sequencing strategy, HDR prostate brachytherapy was simulated on 11 patients with varying number of needle insertions. Sub-optimal needle positioning was simulated at each insertion (modeled by typical random angulation errors). In 91% of the scenarios, the dose distribution improved when the needle was inserted into the most compared to the least sensitive needle track. The computation time for sequencing was less than 6 s per needle track. The proposed needle insertion sequencing can therefore assist in delivering an optimal dose in HDR prostate brachytherapy.

A System Dynamics Model of Serum Prostate-Specific Antigen Screening for Prostate Cancer.

PubMed

Palma, Anton; Lounsbury, David W; Schlecht, Nicolas F; Agalliu, Ilir

2016-02-01

Since 2012, US guidelines have recommended against prostate-specific antigen (PSA) screening for prostate cancer. However, evidence of screening benefit from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening trial and the European Randomized Study of Screening for Prostate Cancer has been inconsistent, due partly to differences in noncompliance and contamination. Using system dynamics modeling, we replicated the PLCO trial and extrapolated follow-up to 20 years. We then simulated 3 scenarios correcting for contamination in the PLCO control arm using Surveillance, Epidemiology, and End Results (SEER) incidence and survival data collected prior to the PSA screening era (scenario 1), SEER data collected during the PLCO trial period (1993-2001) (scenario 2), and data from the European trial's control arm (1991-2005) (scenario 3). In all scenarios, noncompliance was corrected using incidence and survival rates for men with screen-detected cancer in the PLCO screening arm. Scenarios 1 and 3 showed a benefit of PSA screening, with relative risks of 0.62 (95% confidence interval: 0.53, 0.72) and 0.70 (95% confidence interval: 0.59, 0.83) for cancer-specific mortality after 20 years, respectively. In scenario 2, however, there was no benefit of screening. This simulation showed that after correcting for noncompliance and contamination, there is potential benefit of PSA screening in reducing prostate cancer mortality. It also demonstrates the utility of system dynamics modeling for synthesizing epidemiologic evidence to inform public policy. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor, GcMAF1

PubMed Central

Yamamoto, Nobuto; Suyama, Hirofumi; Yamamoto, Nobuyuki

2008-01-01

Serum Gc protein (known as vitamin D3-binding protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of prostate cancer patients was lost or reduced because Gc protein was deglycosylated by serum α-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Therefore, macrophages of prostate cancer patients having deglycosylated Gc protein cannot be activated, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized β-galactosidase and sialidase generated the most potent MAF (termed GcMAF) ever discovered, which produces no adverse effect in humans. Macrophages activated by GcMAF develop a considerable variation of receptors that recognize the abnormality in malignant cell surface and are highly tumoricidal. Sixteen nonanemic prostate cancer patients received weekly administration of 100 ng of GcMAF. As the MAF precursor activity increased, their serum Nagalase activity decreased. Because serum Nagalase activity is proportional to tumor burden, the entire time course analysis for GcMAF therapy was monitored by measuring the serum Nagalase activity. After 14 to 25 weekly administrations of GcMAF (100 ng/week), all 16 patients had very low serum Nagalase levels equivalent to those of healthy control values, indicating that these patients are tumor-free. No recurrence occurred for 7 years. PMID:18633461

Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor, GcMAF.

PubMed

Yamamoto, Nobuto; Suyama, Hirofumi; Yamamoto, Nobuyuki

2008-07-01

Serum Gc protein (known as vitamin D(3)-binding protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of prostate cancer patients was lost or reduced because Gc protein was deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Therefore, macrophages of prostate cancer patients having deglycosylated Gc protein cannot be activated, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generated the most potent MAF (termed GcMAF) ever discovered, which produces no adverse effect in humans. Macrophages activated by GcMAF develop a considerable variation of receptors that recognize the abnormality in malignant cell surface and are highly tumoricidal. Sixteen nonanemic prostate cancer patients received weekly administration of 100 ng of GcMAF. As the MAF precursor activity increased, their serum Nagalase activity decreased. Because serum Nagalase activity is proportional to tumor burden, the entire time course analysis for GcMAF therapy was monitored by measuring the serum Nagalase activity. After 14 to 25 weekly administrations of GcMAF (100 ng/week), all 16 patients had very low serum Nagalase levels equivalent to those of healthy control values, indicating that these patients are tumor-free. No recurrence occurred for 7 years.

Poster - Thur Eve - 55: Monte Carlo simulations of variations in planned dose distributions in a prostate patient population.

PubMed

Balderson, M J; Brown, D W; Quirk, S; Ghasroddashti, E; Kirkby, C

2012-07-01

Clinical outcome studies with clear and objective endpoints are necessary to make informed radiotherapy treatment decisions. Commonly, clinical outcomes are established after lengthy and costly clinical trials are performed and the data are analyzed and published. One the challenges with obtaining meaningful data from clinical trials is that by the time the information gets to the medical profession the results may be less clinically relevant than when the trial began, An alternative approach is to estimate clinical outcomes through patient population modeling. We are developing a mathematical tool that uses Monte Carlo techniques to simulate variations in planned and delivered dose distributions of prostate patients receiving radiotherapy. Ultimately, our simulation will calculate a distribution of Tumor Control Probabilities (TCPs) for a population of patients treated under a given protocol. Such distributions can serve as a metric for comparing different treatment modalities, planning and setup approaches, and machine parameter settings or tolerances with respect to outcomes on broad patient populations. It may also help researchers understand differences one might expect to find before actually doing the clinical trial. As a first step and for the focus of this abstract we wanted to see if we could answer the question: "Can a population of dose distributions of prostate patients be accurately modeled by a set of randomly generated Gaussian functions?" Our results have demonstrated that using a set of randomly generated Gaussian functions can simulate a distribution of prostate patients. © 2012 American Association of Physicists in Medicine.

Prostate cancer epigenetics and its clinical implications

PubMed Central

Yegnasubramanian, Srinivasan

2016-01-01

Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy. PMID:27212125

Prostate cancer epigenetics and its clinical implications.

PubMed

Yegnasubramanian, Srinivasan

2016-01-01

Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy.

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

PubMed

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

Early detection of prostate cancer (PCa) remains a challenging issue. There are studies underway aimed to develop and implement new methods for prostate cancer screening by tumor imaging and obtaining tissue samples from suspicious areas for morphological examination. One of these new methods is shear wave ultrasound elastography (SWUE). The current literature is lacking sufficient coverage of informativeness and specificity of SWUE in the prostate cancer detection, there is no clear criteria for assessing tissue stiffness at different values of PSA and tumor grade, and in prostate hyperplasia and prostatitis. To evaluate the informativeness and specificity of SWUE compared with other diagnostic methods. SWUE has been used in the Clinic of Urology of Sechenov First MSMU since October 2015. During this period, 302 patients were examined using SWUE. SWUE was performed with Aixplorer ultrasound system (Super Sonic Imagine), which provides a single-stage SWUE imaging with both B-mode and real-time mode. The first group (prospective study) included 134 men aged 47 to 81 years with suspected prostate cancer scheduled to either initial or repeat prostate biopsy. PSA levels ranged from 4 to 24 ng/ml. The second group (retrospective study) comprised 120 men with confirmed prostate cancer and PSA levels between 4 and 90 ng/ml. The third group (the control group), comprised 48 healthy men whose PSA level did not exceed 3 ng/ml. All patients of the groups 1 and 2 underwent a standard comprehensive examination. Patients in group 1 were subsequently subjected to transrectal prostate biopsy guided by localization of areas with abnormal tissue stiffness. PCa was detected in 100 of 134 patients. 217 patients of groups 1 and 2 underwent radical prostatectomy. In 28 of them, the match between the cancer location and differentiation in the removed prostate and SWUE findings before surgery was examined. Contrast-enhanced magnetic resonance imaging of pelvic organs was performed in 63 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.

Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers.

PubMed

Guerrero-Bosagna, Carlos; Covert, Trevor R; Haque, Md M; Settles, Matthew; Nilsson, Eric E; Anway, Matthew D; Skinner, Michael K

2012-12-01

The endocrine disruptor vinclozolin has previously been shown to promote epigenetic transgenerational inheritance of adult onset disease in the rat. The current study was designed to investigate the transgenerational actions of vinclozolin on the mouse. Transient exposure of the F0 generation gestating female during gonadal sex determination promoted transgenerational adult onset disease in F3 generation male and female mice, including spermatogenic cell defects, testicular abnormalities, prostate abnormalities, kidney abnormalities and polycystic ovarian disease. Pathology analysis demonstrated 75% of the vinclozolin lineage animals developed disease with 34% having two or more different disease states. Interestingly, the vinclozolin induced transgenerational disease was observed in the outbred CD-1 strain, but not the inbred 129 mouse strain. Analysis of the F3 generation sperm epigenome identified differential DNA methylation regions that can potentially be utilized as epigenetic biomarkers for transgenerational exposure and disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Epigenetic Transgenerational Inheritance of Vinclozolin Induced Mouse Adult Onset Disease and Associated Sperm Epigenome Biomarkers

PubMed Central

Guerrero-Bosagna, Carlos; Covert, Trevor R.; Haque, Md. M.; Settles, Matthew; Nilsson, Eric E.; Anway, Matthew D.; Skinner, Michael K.

2012-01-01

The endocrine disruptor vinclozolin has previously been shown to promote epigenetic transgenerational inheritance of adult onset disease in the rat. The current study was designed to investigate the transgenerational actions of vinclozolin on the mouse. Transient exposure of the F0 generation gestating female during gonadal sex determination promoted transgenerational adult onset disease in F3 generation male and female mice, including spermatogenic cell defects, testicular abnormalities, prostate abnormalities, kidney abnormalities and polycystic ovarian disease. Pathology analysis demonstrated 75% of the vinclozolin lineage animals developed disease with 34% having two or more different disease states. Interestingly, the vinclozolin induced transgenerational disease was observed in the outbred CD-1 strain, but not the inbred 129 mouse strain. Analysis of the F3 generation sperm epigenome identified differential DNA methylation regions that can potentially be utilized as epigenetic biomarkers for transgenerational exposure and disease. PMID:23041264

T2-weighted prostate MRI at 7 Tesla using a simplified external transmit-receive coil array: correlation with radical prostatectomy findings in two prostate cancer patients.

PubMed

Rosenkrantz, Andrew B; Zhang, Bei; Ben-Eliezer, Noam; Le Nobin, Julien; Melamed, Jonathan; Deng, Fang-Ming; Taneja, Samir S; Wiggins, Graham C

2015-01-01

To report design of a simplified external transmit-receive coil array for 7 Tesla (T) prostate MRI, including demonstration of the array for tumor localization using T2-weighted imaging (T2WI) at 7T before prostatectomy. Following simulations of transmitter designs not requiring parallel transmission or radiofrequency-shimming, a coil array was constructed using loop elements, with anterior and posterior rows comprising one transmit-receive element and three receive-only elements. This coil structure was optimized using a whole-body phantom. In vivo sequence optimization was performed to optimize achieved flip angle (FA) and signal to noise ratio (SNR) in prostate. The system was evaluated in a healthy volunteer at 3T and 7T. The 7T T2WI was performed in two prostate cancer patients before prostatectomy, and localization of dominant tumors was subjectively compared with histopathological findings. Image quality was compared between 3T and 7T in these patients. Simulations of the B1(+) field in prostate using two-loop design showed good magnitude (B1(+) of 0.245 A/m/w(1/2)) and uniformity (nonuniformity [SD/mean] of 10.4%). In the volunteer, 90° FA was achieved in prostate using 225 v 1 ms hard-pulse (indicating good efficiency), FA maps confirmed good uniformity (14.1% nonuniformity), and SNR maps showed SNR gain of 2.1 at 7T versus 3T. In patients, 7T T2WI showed excellent visual correspondence with prostatectomy findings. 7T images demonstrated higher estimated SNR (eSNR) in benign peripheral zone (PZ) and tumor compared with 3T, but lower eSNR in fat and slight decreases in tumor-to-PZ contrast and PZ-homogeneity. We have demonstrated feasibility of a simplified external coil array for high-resolution T2-weighted prostate MRI at 7T. © 2013 Wiley Periodicals, Inc.

Target motion tracking in MRI-guided transrectal robotic prostate biopsy.

PubMed

Tadayyon, Hadi; Lasso, Andras; Kaushal, Aradhana; Guion, Peter; Fichtinger, Gabor

2011-11-01

MRI-guided prostate needle biopsy requires compensation for organ motion between target planning and needle placement. Two questions are studied and answered in this paper: 1) is rigid registration sufficient in tracking the targets with an error smaller than the clinically significant size of prostate cancer and 2) what is the effect of the number of intraoperative slices on registration accuracy and speed? we propose multislice-to-volume registration algorithms for tracking the biopsy targets within the prostate. Three orthogonal plus additional transverse intraoperative slices are acquired in the approximate center of the prostate and registered with a high-resolution target planning volume. Both rigid and deformable scenarios were implemented. Both simulated and clinical MRI-guided robotic prostate biopsy data were used to assess tracking accuracy. average registration errors in clinical patient data were 2.6 mm for the rigid algorithm and 2.1 mm for the deformable algorithm. rigid tracking appears to be promising. Three tracking slices yield significantly high registration speed with an affordable error.

A comparison study on various low energy sources in interstitial prostate brachytherapy

PubMed Central

Bakhshabadi, Mahdi; Ghorbani, Mahdi; Knaup, Courtney; Meigooni, Ali S.

2016-01-01

Purpose Low energy sources are routinely used in prostate brachytherapy. 125I is one of the most commonly used sources. Low energy 131Cs source was introduced recently as a brachytherapy source. The aim of this study is to compare dose distributions of 125I, 103Pd, and 131Cs sources in interstitial brachytherapy of prostate. Material and methods ProstaSeed 125I brachytherapy source was simulated using MCNPX Monte Carlo code. Additionally, two hypothetical sources of 103Pd and 131Cs were simulated with the same geometry as the ProstaSeed 125I source, while having their specific emitted gamma spectra. These brachytherapy sources were simulated with distribution of forty-eight seeds in a phantom including prostate. The prostate was considered as a sphere with radius of 1.5 cm. Absolute and relative dose rates were obtained in various distances from the source along the transverse and longitudinal axes inside and outside the tumor. Furthermore, isodose curves were plotted around the sources. Results Analyzing the initial dose profiles for various sources indicated that with the same time duration and air kerma strength, 131Cs delivers higher dose to tumor. However, relative dose rate inside the tumor is higher and outside the tumor is lower for the 103Pd source. Conclusions The higher initial absolute dose in cGy/(h.U) of 131Cs brachytherapy source is an advantage of this source over the others. The higher relative dose inside the tumor and lower relative dose outside the tumor for the 103Pd source are advantages of this later brachytherapy source. Based on the total dose the 125I source has advantage over the others due to its longer half-life. PMID:26985200

A comparison study on various low energy sources in interstitial prostate brachytherapy.

PubMed

Bakhshabadi, Mahdi; Ghorbani, Mahdi; Khosroabadi, Mohsen; Knaup, Courtney; Meigooni, Ali S

2016-02-01

Low energy sources are routinely used in prostate brachytherapy. (125)I is one of the most commonly used sources. Low energy (131)Cs source was introduced recently as a brachytherapy source. The aim of this study is to compare dose distributions of (125)I, (103)Pd, and (131)Cs sources in interstitial brachytherapy of prostate. ProstaSeed (125)I brachytherapy source was simulated using MCNPX Monte Carlo code. Additionally, two hypothetical sources of (103)Pd and (131)Cs were simulated with the same geometry as the ProstaSeed (125)I source, while having their specific emitted gamma spectra. These brachytherapy sources were simulated with distribution of forty-eight seeds in a phantom including prostate. The prostate was considered as a sphere with radius of 1.5 cm. Absolute and relative dose rates were obtained in various distances from the source along the transverse and longitudinal axes inside and outside the tumor. Furthermore, isodose curves were plotted around the sources. Analyzing the initial dose profiles for various sources indicated that with the same time duration and air kerma strength, (131)Cs delivers higher dose to tumor. However, relative dose rate inside the tumor is higher and outside the tumor is lower for the (103)Pd source. The higher initial absolute dose in cGy/(h.U) of (131)Cs brachytherapy source is an advantage of this source over the others. The higher relative dose inside the tumor and lower relative dose outside the tumor for the (103)Pd source are advantages of this later brachytherapy source. Based on the total dose the (125)I source has advantage over the others due to its longer half-life.

Augmentation of the anticancer activity of CYT997 in human prostate cancer by inhibiting Src activity.

PubMed

Teng, Yong; Cai, Yafei; Pi, Wenhu; Gao, Lixia; Shay, Chloe

2017-06-12

Abnormalities of tubulin polymerization and microtubule assembly are often seen in cancer, which make them very suitable targets for the development of therapeutic approach against rapidly dividing and aggressive cancer cells. CYT997 is a novel microtubule-disrupting agent with anticancer activity in multiple cancer types including prostate cancer. However, the molecular mechanisms of action of CYT997 in prostate cancer have not been well characterized. Src knockdown cells were achieved by lentiviral-mediated interference. The drug effects on cell proliferation were measured by MTS. The drug effects on cell viability and death were determined by Cell Titer-Glo® Luminescent cell viability kit and flow cytometry with Zombie Aqua™ staining. The drug effects on apoptosis were assessed by Cell Death Detection Elisa kit and Western blot with a cleaved PARP antibody. The drug effects on cell invasion were examined by Matrigel-coated Boyden chambers. Oxidative stress was detected by DCFH-DA staining and electrochemical biosensor. Mouse models generated by subcutaneous or intracardiac injection were used to investigate the in vivo drug efficacy in tumor growth and metastasis. CYT997 effectively inhibited proliferation, survival, and invasion of prostate cancer cells via blocking multiple oncogenic signaling cascades but not the Src pathway. Inhibition of Src expression by small hairpin RNA or inactivation of Src by dasatinib increased the CYT997-induced cytotoxicity of in vitro. Moreover, the combination of dasatinib and CYT997 exhibited a superior inhibitory effect on tumor growth and metastasis compared with either of the drugs alone. Our findings demonstrate that blockage of Src augments the anticancer effect of CYT997 on prostate cancer and suggest that co-treatment of dasatinib and CYT997 may represent an effective therapeutic regimen for limiting prostate cancer.

NMR spectroscopy of filtered serum of prostate cancer: A new frontier in metabolomics.

PubMed

Kumar, Deepak; Gupta, Ashish; Mandhani, Anil; Sankhwar, Satya Narain

2016-09-01

To address the shortcomings of digital rectal examinations (DRE), serum prostate-specific antigen (PSA), and trans-rectal ultrasound (TRUS) for precise determination of prostate cancer (PC) and differentiation from benign prostatic hyperplasia (BPH), we applied (1) H-nuclear magnetic resonance (NMR) spectroscopy as a surrogate tactic for probing and prediction of PC and BPH. The study comprises 210 filtered sera from suspected PC, BPH, and a healthy subjects' cohort (HC). The filtered serum approach delineates to identify and quantify 52 metabolites using (1) H NMR spectroscopy. All subjects had undergone clinical evaluations (DRE, PSA, and TRUS) followed by biopsy for Gleason score, if needed. NMR-measured metabolites and clinical evaluation data were examined separately using linear multivariate discriminant function analysis (DFA) to probe the signature descriptors for each cohort. DFA indicated that glycine, sarcosine, alanine, creatine, xanthine, and hypoxanthine were able to determine abnormal prostate (BPH + PC). DFA-based classification presented high precision (86.2% by NMR and 68.1% by clinical laboratory method) in discriminating HC from BPH + PC. DFA reveals that alanine, sarcosine, creatinine, glycine, and citrate were able to discriminate PC from BPH. DFA-based categorization exhibited high accuracy (88.3% by NMR and 75.2% by clinical laboratory method) to differentiate PC from BPH. (1) H NMR-based metabolic profiling of filtered-serum sample appears to be assuring, swift, and least-invasive for probing and prediction of PC and BPH with its signature metabolic profile. This novel technique is not only on a par with histopathological evaluation of PC determination but is also comparable to liquid chromatography-based mass spectrometry to identify the metabolites. Prostate 76:1106-1119, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The prostate cancer screening clinic in the Bahamas: a model for low- and middle-income countries.

PubMed

Roberts, Robin; Mitchell, Corydon; Tancawan, Ana Lourdes; Pedican, Mandi; Jones, Glenn Wayne

2017-11-01

Grand Bahama (pop. 51,000) is an island within the Bahamas archipelago. A local chapter of International Us TOO Prostate Cancer Support Group (UTGB) has led an annual community-based prostate cancer screening clinic in Grand Bahama each September since 2009. Features of this initiative, characteristics of attendees, and a description of found cancers were summarized to determine the clinic's value and to guide improvements. We analyzed the established clinic from 2012 to 2015, wherein UTGB attracted corporate funding, volunteers managed clinics, and health professionals provided healthcare services. An explicit algorithm was used to sort clients by age, comorbidities, and findings from digital rectal examinations, and prostate-specific antigen (PSA) values, to determine which clients would undergo secondary assessment and prostate biopsy. Overall, 1,844 males were registered (mean age 57.6 years), and only 149 men attended on more than one occasion for a total of 1,993 clinic visit. The urologist reviewed 315 men in secondary follow-up, for elevated PSA and/or an abnormal digital rectal examination. Of these, 45 men fulfilled criteria for trans-rectal ultrasound biopsy, and there were 40 found cases of prostate cancer, for a positive-predictive value of 89%. By D'Amico risk-stratification, these 40 cases were low (10%), intermediate (40%), and high risk (50%). The urologist counseled all 40 cases and facilitated access to standard care. This study suggests that low-resource countries can advance cost-effective screening clinics, apply policy guidelines, and provide services within acceptable standards of care. It is the expectation, with a sustained effort and community participation over the ensuing years, that earlier disease presentation will occur and, consequently, a concomitant decrease in the disease-specific mortality.

Urinary Volatile Organic Compounds for the Detection of Prostate Cancer

PubMed Central

Khalid, Tanzeela; Aggio, Raphael; White, Paul; De Lacy Costello, Ben; Persad, Raj; Al-Kateb, Huda; Jones, Peter; Probert, Chris S.; Ratcliffe, Norman

2015-01-01

The aim of this work was to investigate volatile organic compounds (VOCs) emanating from urine samples to determine whether they can be used to classify samples into those from prostate cancer and non-cancer groups. Participants were men referred for a trans-rectal ultrasound-guided prostate biopsy because of an elevated prostate specific antigen (PSA) level or abnormal findings on digital rectal examination. Urine samples were collected from patients with prostate cancer (n = 59) and cancer-free controls (n = 43), on the day of their biopsy, prior to their procedure. VOCs from the headspace of basified urine samples were extracted using solid-phase micro-extraction and analysed by gas chromatography/mass spectrometry. Classifiers were developed using Random Forest (RF) and Linear Discriminant Analysis (LDA) classification techniques. PSA alone had an accuracy of 62–64% in these samples. A model based on 4 VOCs, 2,6-dimethyl-7-octen-2-ol, pentanal, 3-octanone, and 2-octanone, was marginally more accurate 63–65%. When combined, PSA level and these four VOCs had mean accuracies of 74% and 65%, using RF and LDA, respectively. With repeated double cross-validation, the mean accuracies fell to 71% and 65%, using RF and LDA, respectively. Results from VOC profiling of urine headspace are encouraging and suggest that there are other metabolomic avenues worth exploring which could help improve the stratification of men at risk of prostate cancer. This study also adds to our knowledge on the profile of compounds found in basified urine, from controls and cancer patients, which is useful information for future studies comparing the urine from patients with other disease states. PMID:26599280

Management of benign prostatic hyperplasia with silodosin

PubMed Central

Yamanishi, Tomonori; Mizuno, Tomoya; Kamai, Takao; Yoshida, Ken-Ichiro; Sakakibara, Ryuji; Uchiyama, Tomoyuki

2009-01-01

It has been reported that blockade of α1A-adrenoceptor (AR) relieves bladder outlet obstruction, while blockade of α1D-AR is believed to alleviate storage symptoms due to detrusor overactivity. Silodosin, (−)-1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2trifluoroethoxy) phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7- carboxamide, is a new α1A-AR selective antagonist. Silodosin is highly selective for the α1A-AR subtype, showing an affinity for the α1A-AR that is 583- and 55.5-fold higher than its affinity for the α1B-and α1D-ARs, respectively. In randomized, double-blind, placebo-controlled phase III studies performed in Japan and the United States, silodosin has been shown to be effective for both storage and voiding symptoms associated with benign prostatic hyperplasia. Early effects of silodosin (after 2–6 hours or day 1) on lower urinary tract symptoms have also been reported. In urodynamic studies, detrusor overactivity disappeared in 40% and improved in 35% of patients after administration. In pressure flow studies, the grade of obstruction on the International Continence Society nomogram showed improvement in 56% of patients. The rate of adverse events in the silodosin, tamsulosin and placebo groups was 88.6%, 82.3%, and 71.6%, respectively. The most common adverse event was (mostly mild) abnormal ejaculation (28.1%). However, few patients (2.8%) discontinued silodosin because of abnormal ejaculation. Orthostatic hypotension showed a similar incidence in the silodosin (2.6%) and placebo (1.5%) groups. In conclusion, silodosin improves detrusor overactivity and obstruction and thus may be effective for both storage and voiding symptoms in patients with benign prostatic hyperplasia. PMID:24198606

MO-B-BRC-01: Introduction [Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prisciandaro, J.

2016-06-15

Brachytherapy has proven to be an effective treatment option for prostate cancer. Initially, prostate brachytherapy was delivered through permanently implanted low dose rate (LDR) radioactive sources; however, high dose rate (HDR) temporary brachytherapy for prostate cancer is gaining popularity. Needle insertion during prostate brachytherapy is most commonly performed under ultrasound (U/S) guidance; however, treatment planning may be performed utilizing several imaging modalities either in an intra- or post-operative setting. During intra-operative prostate HDR, the needles are imaged during implantation, and planning may be performed in real time. At present, the most common imaging modality utilized for intra-operative prostate HDR ismore » U/S. Alternatively, in the post-operative setting, following needle implantation, patients may be simulated with computed tomography (CT) or magnetic resonance imaging (MRI). Each imaging modality and workflow provides its share of benefits and limitations. Prostate HDR has been adopted in a number of cancer centers across the nation. In this educational session, we will explore the role of U/S, CT, and MRI in HDR prostate brachytherapy. Example workflows and operational details will be shared, and we will discuss how to establish a prostate HDR program in a clinical setting. Learning Objectives: Review prostate HDR techniques based on the imaging modality Discuss the challenges and pitfalls introduced by the three imagebased options for prostate HDR brachytherapy Review the QA process and learn about the development of clinical workflows for these imaging options at different institutions.« less

Endocrine Disruptor Vinclozolin Induced Epigenetic Transgenerational Adult-Onset Disease

PubMed Central

Anway, Matthew D.; Leathers, Charles; Skinner, Michael K.

2018-01-01

The fetal basis of adult disease is poorly understood on a molecular level and cannot be solely attributed to genetic mutations or a single etiology. Embryonic exposure to environmental compounds has been shown to promote various disease states or lesions in the first generation (F1). The current study used the endocrine disruptor vinclozolin (antiandrogenic compound) in a transient embryonic exposure at the time of gonadal sex determination in rats. Adult animals from the F1 generation and all subsequent generations examined (F1–F4) developed a number of disease states or tissue abnormalities including prostate disease, kidney disease, immune system abnormalities, testis abnormalities, and tumor development (e.g. breast). In addition, a number of blood abnormalities developed including hypercholesterolemia. The incidence or prevalence of these transgenerational disease states was high and consistent across all generations (F1–F4) and, based on data from a previous study, appears to be due in part to epigenetic alterations in the male germ line. The observations demonstrate that an environmental compound, endocrine disruptor, can induce transgenerational disease states or abnormalities, and this suggests a potential epigenetic etiology and molecular basis of adult onset disease. PMID:16973726

Multiparametric MRI followed by targeted prostate biopsy for men with suspected prostate cancer: a clinical decision analysis

PubMed Central

Willis, Sarah R; Ahmed, Hashim U; Moore, Caroline M; Donaldson, Ian; Emberton, Mark; Miners, Alec H; van der Meulen, Jan

2014-01-01

Objective To compare the diagnostic outcomes of the current approach of transrectal ultrasound (TRUS)-guided biopsy in men with suspected prostate cancer to an alternative approach using multiparametric MRI (mpMRI), followed by MRI-targeted biopsy if positive. Design Clinical decision analysis was used to synthesise data from recently emerging evidence in a format that is relevant for clinical decision making. Population A hypothetical cohort of 1000 men with suspected prostate cancer. Interventions mpMRI and, if positive, MRI-targeted biopsy compared with TRUS-guided biopsy in all men. Outcome measures We report the number of men expected to undergo a biopsy as well as the numbers of correctly identified patients with or without prostate cancer. A probabilistic sensitivity analysis was carried out using Monte Carlo simulation to explore the impact of statistical uncertainty in the diagnostic parameters. Results In 1000 men, mpMRI followed by MRI-targeted biopsy ‘clinically dominates’ TRUS-guided biopsy as it results in fewer expected biopsies (600 vs 1000), more men being correctly identified as having clinically significant cancer (320 vs 250), and fewer men being falsely identified (20 vs 50). The mpMRI-based strategy dominated TRUS-guided biopsy in 86% of the simulations in the probabilistic sensitivity analysis. Conclusions Our analysis suggests that mpMRI followed by MRI-targeted biopsy is likely to result in fewer and better biopsies than TRUS-guided biopsy. Future research in prostate cancer should focus on providing precise estimates of key diagnostic parameters. PMID:24934207

Biothermal modeling of transurethral ultrasound applicators for MR-guided prostate thermal therapy (Invited Paper)

NASA Astrophysics Data System (ADS)

Ross, Anthony B.; Diederich, Chris J.; Nau, William H.; Tyreus, Per D.; Gill, Harcharan; Bouley, Donna; Butts, R. K.; Rieke, Viola; Daniel, Bruce; Sommer, Graham

2005-04-01

Thermal ablation is a minimally-invasive treatment option for benign prostatic hyperplasia (BPH) and localized prostate cancer. Accurate spatial control of thermal dose delivery is paramount to improving thermal therapy efficacy and avoiding post-treatment complications. We have recently developed three types of transurethral ultrasound applicators, each with different degrees of heating selectivity. These applicators have been evaluated in vivo in coordination with magnetic resonance temperature imaging, and demonstrated to accurately ablate specific regions of the canine prostate. A finite difference biothermal model of the three types of transurethral ultrasound applicators (sectored tubular, planar, and curvilinear transducer sections) was developed and used to further study the performance and heating capabilities of each these devices. The biothermal model is based on the Pennes bioheat equation. The acoustic power deposition pattern corresponding to each applicator type was calculated using the rectangular radiator approximation to the Raleigh Sommerfield diffraction integral. In this study, temperature and thermal dose profiles were calculated for different treatment schemes and target volumes, including single shot and angular scanning procedures. This study also demonstrated the ability of the applicators to conform the cytotoxic thermal dose distribution to a predefined target area. Simulated thermal profiles corresponded well with MR temperature images from previous in vivo experiments. Biothermal simulations presented in this study reinforce the potential of improved efficacy of transurethral ultrasound thermal therapy of prostatic disease.

Texture analysis of tissues in Gleason grading of prostate cancer

NASA Astrophysics Data System (ADS)

Alexandratou, Eleni; Yova, Dido; Gorpas, Dimitris; Maragos, Petros; Agrogiannis, George; Kavantzas, Nikolaos

2008-02-01

Prostate cancer is a common malignancy among maturing men and the second leading cause of cancer death in USA. Histopathological grading of prostate cancer is based on tissue structural abnormalities. Gleason grading system is the gold standard and is based on the organization features of prostatic glands. Although Gleason score has contributed on cancer prognosis and on treatment planning, its accuracy is about 58%, with this percentage to be lower in GG2, GG3 and GG5 grading. On the other hand it is strongly affected by "inter- and intra observer variations", making the whole process very subjective. Therefore, there is need for the development of grading tools based on imaging and computer vision techniques for a more accurate prostate cancer prognosis. The aim of this paper is the development of a novel method for objective grading of biopsy specimen in order to support histopathological prognosis of the tumor. This new method is based on texture analysis techniques, and particularly on Gray Level Co-occurrence Matrix (GLCM) that estimates image properties related to second order statistics. Histopathological images of prostate cancer, from Gleason grade2 to Gleason grade 5, were acquired and subjected to image texture analysis. Thirteen texture characteristics were calculated from this matrix as they were proposed by Haralick. Using stepwise variable selection, a subset of four characteristics were selected and used for the description and classification of each image field. The selected characteristics profile was used for grading the specimen with the multiparameter statistical method of multiple logistic discrimination analysis. The subset of these characteristics provided 87% correct grading of the specimens. The addition of any of the remaining characteristics did not improve significantly the diagnostic ability of the method. This study demonstrated that texture analysis techniques could provide valuable grading decision support to the pathologists, concerning prostate cancer prognosis.

Analysis of histological findings obtained combining US/mp-MRI fusion-guided biopsies with systematic US biopsies: mp-MRI role in prostate cancer detection and false negative.

PubMed

Faiella, Eliodoro; Santucci, Domiziana; Greco, Federico; Frauenfelder, Giulia; Giacobbe, Viola; Muto, Giovanni; Zobel, Bruno Beomonte; Grasso, Rosario Francesco

2018-02-01

To evaluate the diagnostic accuracy of mp-MRI correlating US/mp-MRI fusion-guided biopsy with systematic random US-guided biopsy in prostate cancer diagnosis. 137 suspected prostatic abnormalities were identified on mp-MRI (1.5T) in 96 patients and classified according to PI-RADS score v2. All target lesions underwent US/mp-MRI fusion biopsy and prostatic sampling was completed by US-guided systematic random 12-core biopsies. Histological analysis and Gleason score were established for all the samples, both target lesions defined by mp-MRI, and random biopsies. PI-RADS score was correlated with the histological results, divided in three groups (benign tissue, atypia and carcinoma) and with Gleason groups, divided in four categories considering the new Grading system of the ISUP 2014, using t test. Multivariate analysis was used to correlate PI-RADS and Gleason categories to PSA level and abnormalities axial diameter. When the random core biopsies showed carcinoma (mp-MRI false-negatives), PSA value and lesions Gleason median value were compared with those of carcinomas identified by mp-MRI (true-positives), using t test. There was statistically significant difference between PI-RADS score in carcinoma, atypia and benign lesions groups (4.41, 3.61 and 3.24, respectively) and between PI-RADS score in Gleason < 7 group and Gleason > 7 group (4.14 and 4.79, respectively). mp-MRI performance was more accurate for lesions > 15 mm and in patients with PSA > 6 ng/ml. In systematic sampling, 130 (11.25%) mp-MRI false-negative were identified. There was no statistic difference in Gleason median value (7.0 vs 7.06) between this group and the mp-MRI true-positives, but a significant lower PSA median value was demonstrated (7.08 vs 7.53 ng/ml). mp-MRI remains the imaging modality of choice to identify PCa lesions. Integrating US-guided random sampling with US/mp-MRI fusion target lesions sampling, 3.49% of false-negative were identified.

Imaging Prostate Cancer Microenvironment by Collagen Hybridization

DTIC Science & Technology

2016-10-01

affinity to denatured collagens and collagens undergoing remodeling which simulate the microenvironment of metastatic tumors. We will focus on previously...specifically target digested collagens with unfolded and partially denatured collagen triple helices. 2. Demonstration of ex vivo and in vivo targeting...invasive prostate cancer due to the absence of non-specific affinity and high propensity to hybridize with denatured collagen strand (Aim 1). We

Long term organ culture of human prostate tissue in a NASA-designed rotating wall bioreactor

NASA Technical Reports Server (NTRS)

Margolis, L.; Hatfill, S.; Chuaqui, R.; Vocke, C.; Emmert-Buck, M.; Linehan, W. M.; Duray, P. H.

1999-01-01

PURPOSE: To maintain ex vivo integral prostatic tissue including intact stromal and ductal elements using the NASA-designed Rotating Wall Vessel (RWV) which maintains colocalized cells in an environment that promotes both three-dimensional cellular interactions together with the uniform mass transfer of nutrients and metabolic wastes. MATERIALS AND METHODS: Samples of normal prostate were obtained as a byproduct of transurethral prostatectomy or needle biopsy. Prostatic tissue dissected into small 1 x 1 mm. blocks was cultured in the Rotating Wall Vessel (RWV) Bioreactor for various time periods and analyzed using histological, immunochemical, and total cell RNA assays. RESULTS: We report the long term maintenance of benign explanted human prostate tissue grown in simple culture medium, under the simulated microgravity conditions afforded by the RWV bioreactor. Mesenchymal stromal elements including blood vessels and architecturally preserved tubuloglandular acini were maintained for a minimum of 28 days. Cytokeratins, vimentin and TGF-beta2 receptor and ligand were preserved through the entire culture period as revealed by immunocytochemistry. Prostatic acid phosphatase (PAP) was continuously expressed during the culture period, although somewhat decreased. Prostatic specific antigen (PSA) and its transcript were down regulated over time of culture. Prostatic carcinoma cells from the TSU cell line were able to invade RWV-cultured benign prostate tissue explants. CONCLUSIONS: The RWV bioreactor represents an additional new technology for culturing prostate tissue for further investigations concerning the basic physiology and pathobiology of this clinically important tissue.

The impact of race on prostate cancer detection and choice of treatment in men undergoing a contemporary extended biopsy approach.

PubMed

Swords, Kelly; Wallen, Eric M; Pruthi, Raj S

2010-01-01

African American men have a higher rate of prostate cancer mortality compared with their Caucasian American counterparts. However, it remains unclear as to whether such differences are due to biologic or socioeconomic influences. This study sought to determine if there are differences in demographic and clinical characteristics between African American and Caucasian American men in a modern cohort undergoing extended biopsy approach, and evaluated the subsequent choice of therapy in patients diagnosed with prostate cancer. A retrospective review was performed from a consecutive series of 500 men undergoing prostate biopsy at our institution between 2003 and 2005. All patients underwent a contemporary 10-12 biopsy scheme. Demographic, clinical, and pathologic variables as well as treatment choice (those with positive biopsy) were stratified and evaluated with regard to race-African American, Caucasian American, and other (Hispanic, Asian, American Indian). 65% were Caucasian American, 29% African American, and 7% other. The overall positive biopsy rate was 44%. African American men were significantly younger than Caucasian American but were not younger than "other" (61.6 vs. 64.3 vs. 61.5 years). No differences were observed with regard to prostate specific antigen density (PSAD), prostate volume, or rate of abnormal digital rectal exam (DRE). The positive biopsy rate was not different between Caucasian American and African American (46% vs. 46%), but significantly lower in other men (16%). These differences were maintained on odds ratio modeling, including age-adjusted and multivariate models. Of the 223 men with positive biopsies, information on treatment choice demonstrated that African American men had a significantly higher rate of choice of XRT (OR = 2.12) and rate of avoidance of surgery (OR = 0.35) than Caucasian American men. In men undergoing prostate biopsy using an extended (10-12 core) biopsy scheme, no differences were observed with regard to positive biopsy rate or other clinical or biochemical parameters [except for age and prostate specific antigen (PSA) level] between African American and Caucasian American men. Of those with a positive biopsy, African American men were more likely to avoid surgery and choose XRT in our population. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Virus Delivery of CRISPR Guides to the Murine Prostate for Gene Alteration.

PubMed

Riedel, Maria; Berthelsen, Martin F; Bakiri, Latifa; Wagner, Erwin F; Thomsen, Martin K

2018-04-27

With an increasing incidence of prostate cancer, identification of new tumor drivers or modulators is crucial. Genetically engineered mouse models (GEMM) for prostate cancer are hampered by tumor heterogeneity and its complex microevolution dynamics. Traditional prostate cancer mouse models include, amongst others, germline and conditional knockouts, transgenic expression of oncogenes, and xenograft models. Generation of de novo mutations in these models is complex, time-consuming, and costly. In addition, most of traditional models target the majority of the prostate epithelium, whereas human prostate cancer is well known to evolve as an isolated event in only a small subset of cells. Valuable models need to simulate not only prostate cancer initiation, but also progression to advanced disease. Here we describe a method to target a few cells in the prostate epithelium by transducing cells by viral particles. The delivery of an engineered virus to the murine prostate allows alteration of gene expression in the prostate epithelia. Virus type and quantity will hereby define the number of targeted cells for gene alteration by transducing a few cells for cancer initiation and many cells for gene therapy. Through surgery-based injection in the anterior lobe, distal from the urinary track, the tumor in this model can expand without impairing the urinary function of the animal. Furthermore, by targeting only a subset of prostate epithelial cells the technique enables clonal expansion of the tumor, and therefore mimics human tumor initiation, progression, as well as invasion through the basal membrane. This novel technique provides a powerful prostate cancer model with improved physiological relevance. Animal suffering is limited, and since no additional breeding is required, overall animal count is reduced. At the same time, analysis of new candidate genes and pathways is accelerated, which in turn is more cost efficient.

Fluorine-18-fluoroethylcholine PET/CT in the detection of prostate cancer: a South African experience.

PubMed

Vorster, Mariza; Modiselle, Moshe; Ebenhan, Thomas; Wagener, Carl; Sello, That; Zeevaart, Jan Rijn; Moshokwa, Evelyn; Sathekge, Mike Machaba

2015-01-01

Imaging with fluorine-18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) has, until recently provided disappointing results with low sensitivity ranging from 31%-64% in patients with well-differentiated prostate cancer (PC) at all prostatic specific antigen (PSA) levels while fluorine-18-fluoroethylcholine ((18)F-FECh) PET/CT showed about 85% sensitivity in restaging patients after relapse. We present our experience of the sensitivity of (18)F-FECh PET/CT in the early stages of PC. Fifty patients were prospectively recruited and imaged, of which 40 fulfilled all inclusion criteria. Our patients had an average age of 65.5 years. Fifteen patients were referred for initial staging, with the remaining 25 referred for restaging and all patients had histologically confirmed adenocarcinoma. Patients were imaged by (18)F-FECh PET/CT. Findings were evaluated qualitatively and quantitatively and compared to the results of histology, PSA, Gleason score and bone scintigraphy. The prostate SUVmax was also used. Thirty-one patients demonstrated abnormal pelvic- and or extra- pelvic findings on (18)F-FECh PET/CT, which was consistent with malignant or metastatic involvement. The prostate SUVmax could not be used to predict the presence or absence of metastatic disease. Findings of this paper suggest that (18)F-FECh PET/CT in 30/40 cases (estimated as 75%) was helpful in the initial staging, restaging and lymph node detection of patients with PC. The SUVmax was not helpful. We diagnosed more PC cases in our African-American patients as compared to the Caucasian patients.

Effect of Strain Restored Energy on Abnormal Grain Growth in Mg Alloy Simulated by Phase Field Methods

NASA Astrophysics Data System (ADS)

Wu, Yan; Huang, Yuan-yuan

2018-03-01

Abnormal grain growth of single phase AZ31 Mg alloy in the spatio-temporal process has been simulated by phase field models, and the influencing factors of abnormal grain growth are studied in order to find the ways to control secondary recrystallization in the microstructure. The study aims to find out the mechanisms for abnormal grain growth in real alloys. It is shown from the simulated results that the abnormal grain growth can be controlled by the strain restored energy. Secondary recrystallization after an annealing treatment can be induced if there are grains of a certain orientation in the microstructure with local high restored energy. However, if the value of the local restored energy at a certain grain orientation is not greater than 1.1E 0, there may be no abnormal grain growth in the microstructure.

Hormone escape is associated with genomic instability in a human prostate cancer model.

PubMed

Legrier, Marie-Emmanuelle; Guyader, Charlotte; Céraline, Jocelyn; Dutrillaux, Bernard; Oudard, Stéphane; Poupon, Marie-France; Auger, Nathalie

2009-03-01

Lack of hormone dependency in prostate cancers is an irreversible event that occurs through generation of genomic instability induced by androgen deprivation. Indeed, the cytogenetic profile of hormone-dependent (HD) prostate cancer remains stable as long as it received a hormone supply, whereas the profile of hormone-independent (HID) variants acquired new and various alterations. This is demonstrated here using a HD xenografted model of a human prostate cancer, PAC120, transplanted for 11 years into male nude mice and 4 HID variants obtained by surgical castration. Cytogenetic analysis, done by karyotype, FISH, CGH and array-CGH, shows that PAC120 at early passage presents numerous chromosomal alterations. Very few additional alterations were found between the 5th and 47th passages, indicating the stability of the parental tumor. HID variants largely maintained the core of chromosomal alterations of PAC120 - losses at 6q, 7p, 12q, 15q and 17q sites. However, each HID variant displayed a number of new alterations, almost all being specific to each variant and very few shared by all. None of the HID had androgen receptor mutations. Our study indicates that hormone castration is responsible for genomic instability generating new cytogenetic abnormalities susceptible to alter the properties of cancer cell associated with tumor progression, such as increased cell survival and ability to metastasize.

Chronic Pelvic Pain: Neurogenic or Non-Neurogenic? Warm Detection Threshold Testing Supports a Diagnosis of Pudendal Neuropathy.

PubMed

Antolak, Stanley J; Antolak, Christopher M

2018-03-01

Chronic pelvic pain (CPP) in men is rarely considered to have a neurogenic (neuropathic) basis. Separation of neurogenic from non-neurogenic pain is possible using clinical examination and neurophysiologic tests. A definite diagnosis of neuropathic pain can be made. We aim to demonstrate that definite pudendal neuropathic abnormalities can be supported by a quantitative sensory test (QST) called the warm temperature threshold detection (WDT) test in men with CPP. This is a retrospective review of 25 consecutive, unrecruited men evaluated in a private clinical practice beginning on January 1, 2010. The techniques of examination and neurophysiological testing have been standard since 2003. A private practice that is a referral center because of its focus on CPP of a neuropathic basis. Pinprick sensation was evaluated at 6 sites in the pudendal nerve territory (3 branches on each side). A WDT was performed at each nerve branch using a Physitemp NTE-2C Thermoprobe and Controller. This used a stepping algorithm from a neutral baseline of 31.5°C. Quantitative and subjective "qualitative responses" were recorded. Our preferred symptom score to evaluate pain level at consultation is the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). The results become the benchmark for comparison of responses following future treatments (not discussed). When possible, microscopy was used to evaluate prostate secretions for inflammatory prostatitis except in 2 men with CPP who had undergone previous radical prostatectomy for cancer. Observations were made of the skin in the pudendal territory. Our specific evaluation for neuropathy also sought evidence of multiple additional neuropathic pelvic pain generators. The WDT was abnormal in all men (88% quantitative), and pinprick sensation was abnormal in 92% of the men. The combination of tests provided a diagnosis of pudendal neuropathy in all patients, resulting in an accurate and timely explanation of the neurogenic basis of their CPP symptoms. The NIH-CPSI scores ranged from 10 to 35 (median 25). Four of 15 men had inflammatory prostatitis in addition to pudendal neuropathy. There is selection bias because the men were either self-referred, suspecting their diagnosis from internet searches, or were referred by physicians who were aware of the focus of this clinical practice. The warm temperature testing used established normal values for the men. The NIH-CPSI does not evaluate sexual or bowel symptoms. Sensitivity or specificity values for the tests could not be obtained. A possible neuropathic basis for CPP in men can be suspected from symptoms and history of activities. A probable diagnosis of neuropathy can be determined using a pinprick sensory evaluation in the pudendal territory. A definite diagnosis of pudendal neuropathy can be made using WDT. The combination of these 2 examinations demonstrated pudendal neuropathy in 100% of this cohort.The institutional review board deemed this study met criteria for exemption. Chronic pelvic pain, pudendal neuropathy, quantitative sensory testing, warm temperature detection threshold test, neuropathic pelvic pain, definite diagnosis of neuropathy, chronic prostatitis.

Utilization of the k-space Computational Method to Design an Intracavitary Transrectal Ultrasound Phased Array Applicator for Hyperthermia Treatment of Prostate Cancer

NASA Astrophysics Data System (ADS)

Al-Bataineh, Osama M.; Collins, Christopher M.; Sparrow, Victor W.; Keolian, Robert M.; Smith, Nadine Barrie

2006-05-01

This research utilizes the k-space computational method to design an intracavitary probe for hyperthermia treatment of prostate cancer. A three-dimensional (3D) photographical prostate model, utilizing imaging data from the Visible Human Project®, was the basis for inhomogeneous acoustical model development. The acoustical model accounted for sound speed, density, and absorption variations. The k-space computational method was used to simulate ultrasound wave propagation of the designed phased array through the acoustical model. To insure the uniformity and spread of the pressure in the length of the array, and the steering and focusing capability in the width of the array, the equal-sized elements of the phased array were 1 × 14 mm. The anatomical measurements of the prostate were used to predict the final phased array specifications (4 × 20 planar array, 1.2 MHz, element size = 1 × 14 mm, array size = 56 × 20 mm). Good agreement between the exposimetry and the k-space results was achieved. As an example, the -3 dB distances of the focal volume were differing by 9.1% in the propagation direction for k-space prostate simulation and exposimetry results. Temperature simulations indicated that the rectal wall temperature was elevated less than 2°C during hyperthermia treatment. Steering and focusing ability of the designed probe, in both azimuth and propagation directions, were found to span the entire prostate volume with minimal grating lobes (-10 dB reduction from the main lobe) and least heat damage to the rectal wall. Evaluations of the probe included ex vivo and in vivo controlled experiments to deliver the required thermal dose to the targeted tissue. With a desired temperature plateau of 43.0°C, the MRI temperature results at the steady state were 42.9 ± 0.38°C and 43.1 ± 0.80°C for ex vivo and in vivo experiments, respectively. Unlike conventional computational methods, the k-space method provides a powerful tool to predict pressure wavefield and temperature rise in sophisticated, large scale, 3D, inhomogeneous and coarse grid models.

Quantitative Measures for Evaluation of Ultrasound Therapies of the Prostate

NASA Astrophysics Data System (ADS)

Kobelevskiy, Ilya; Burtnyk, Mathieu; Bronskill, Michael; Chopra, Rajiv

2010-03-01

Development of non-invasive techniques for prostate cancer treatment requires implementation of quantitative measures for evaluation of the treatment results. In this paper. we introduce measures that estimate spatial targeting accuracy and potential thermal damage to the structures surrounding the prostate. The measures were developed for the technique of treating prostate cancer with a transurethral ultrasound heating applicators guided by active MR temperature feedback. Variations of ultrasound element length and related MR imaging parameters such as MR slice thickness and update time were investigated by performing numerical simulations of the treatment on a database of ten patient prostate geometries segmented from clinical MR images. Susceptibility of each parameter configuration to uncertainty in MR temperature measurements was studied by adding noise to the temperature measurements. Gaussian noise with zero mean and standard deviation of 0, 1, 3 and 5° C was used to model different levels of uncertainty in MR temperature measurements. Results of simulations for each parameter configuration were averaged over the database of the ten prostate patient geometries studied. Results have shown that for update time of 5 seconds both 3- and 5-mm elements achieve appropriate performance for temperature uncertainty up to 3° C, while temperature uncertainty of 5° C leads to noticeable reduction in spatial accuracy and increased risk of damaging rectal wall. Ten-mm elements lacked spatial accuracy and had higher risk of damaging rectal wall compared to 3- and 5-mm elements, but were less sensitive to the level of temperature uncertainty. The effect of changing update time was studied for 5-mm elements. Simulations showed that update time had minor effects on all aspects of treatment for temperature uncertainty of 0° C and 1° C, while temperature uncertainties of 3° C and 5° C led to reduced spatial accuracy, increased potential damage to the rectal wall, and longer treatment times for update time above 5 seconds. Overall evaluation of results suggested that 5-mm elements showed best performance under physically reachable MR imaging parameters.

Study of two different radioactive sources for prostate brachytherapy treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pereira Neves, Lucio; Perini, Ana Paula; Souza Santos, William de

In this study we evaluated two radioactive sources for brachytherapy treatments. Our main goal was to quantify the absorbed doses on organs and tissues of an adult male patient, submitted to a brachytherapy treatment with two radioactive sources. We evaluated a {sup 192}Ir and a {sup 125}I radioactive sources. The {sup 192}Ir radioactive source is a cylinder with 0.09 cm in diameter and 0.415 cm long. The {sup 125}I radioactive source is also a cylinder, with 0.08 cm in diameter and 0.45 cm long. To evaluate the absorbed dose distribution on the prostate, and other organs and tissues of anmore » adult man, a male virtual anthropomorphic phantom MASH, coupled in the radiation transport code MCNPX 2.7.0, was employed.We simulated 75, 90 and 102 radioactive sources of {sup 125}I and one of {sup 192}Ir, inside the prostate, as normally used in these treatments, and each treatment was simulated separately. As this phantom was developed in a supine position, the displacement of the internal organs of the chest, compression of the lungs and reduction of the sagittal diameter were all taken into account. For the {sup 192}Ir, the higher doses values were obtained for the prostate and surrounding organs, as the colon, gonads and bladder. Considering the {sup 125}I sources, with photons with lower energies, the doses to organs that are far from the prostate were lower. All values for the dose rates are in agreement with those recommended for brachytherapy treatments. Besides that, the new seeds evaluated in this work present usefulness as a new tool in prostate brachytherapy treatments, and the methodology employed in this work may be applied for other radiation sources, or treatments. (authors)« less

Virtual patients: development in cancer nursing education.

PubMed

Moule, Pam; Pollard, Katherine; Armoogum, Julie; Messer, Simon

2015-07-01

The number of men diagnosed with prostate cancer is increasing and internationally there are high incidence rates. It is important that nurses and healthcare professionals are enabled to provide appropriate care to those men affected by prostate cancer and their families. Despite this need, there is recognition that many professionals feel ill prepared and lack knowledge in a number of areas. This paper presents the development of a Virtual Patient (VP) online resource to support practitioner learning. To develop five online VP simulation scenarios to meet the learning needs of nurses and health-care professionals caring for men with prostate cancer. Topic areas for the VPs were taken from previous work exploring the needs of health care professionals working with men with prostate cancer. An initial scoping exercise involving nursing practitioners, students and a prostate cancer charity confirmed the focus of the case study scenarios. Service users and specialist practitioners reviewed an outline of each case study to ensure fidelity of the simulations scenarios. Cases were entered into UChoose, a web based interactive VP player and authoring tool. The final case studies were reviewed by a sample of both registered and non-registered nurses and nursing students. The majority of respondents reported an increase in knowledge and suggested that they would recommend the resource to others. A number of positive aspects of the resource were highlighted. Respondents also commented about areas of weakness, a number of which have been addressed subsequently. The VP case studies provided an opportunity to develop knowledge and confidence in caring for men with prostate cancer. The mode of delivery and the content was acceptable for less experienced and knowledgeable staff. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Mechanosensory Ca2+ Channel as a Central Regulator of Prostate Tumor Cell Migration and Invasiveness

DTIC Science & Technology

2008-01-01

contribute to major human diseases, including muscular dystrophy, kidney disease, cardiac arrhythmias, hyper- tension, and tumor cell invasion...explain why the absence of dystrophin in Duchenne muscular dystrophic muscle results in TRPC1 channels being abnormally gated open (Section VIII.A.3... Muscular Dystrophy BothTRPC1andMscCa are expressed in skeletalmuscle and bothhave been implicated in the muscular degeneration that occurs in Duchenne

Effect of endorectal balloon positioning errors on target deformation and dosimetric quality during prostate SBRT

NASA Astrophysics Data System (ADS)

Jones, Bernard L.; Gan, Gregory; Kavanagh, Brian; Miften, Moyed

2013-11-01

An inflatable endorectal balloon (ERB) is often used during stereotactic body radiation therapy (SBRT) for treatment of prostate cancer in order to reduce both intrafraction motion of the target and risk of rectal toxicity. However, the ERB can exert significant force on the prostate, and this work assessed the impact of ERB position errors on deformation of the prostate and treatment dose metrics. Seventy-one cone-beam computed tomography (CBCT) image datasets of nine patients with clinical stage T1cN0M0 prostate cancer were studied. An ERB (Flexi-Cuff, EZ-EM, Westbury, NY) inflated with 60 cm3 of air was used during simulation and treatment, and daily kilovoltage (kV) CBCT imaging was performed to localize the prostate. The shape of the ERB in each CBCT was analyzed to determine errors in position, size, and shape. A deformable registration algorithm was used to track the dose received by (and deformation of) the prostate, and dosimetric values such as D95, PTV coverage, and Dice coefficient for the prostate were calculated. The average balloon position error was 0.5 cm in the inferior direction, with errors ranging from 2 cm inferiorly to 1 cm superiorly. The prostate was deformed primarily in the AP direction, and tilted primarily in the anterior-posterior/superior-inferior plane. A significant correlation was seen between errors in depth of ERB insertion (DOI) and mean voxel-wise deformation, prostate tilt, Dice coefficient, and planning-to-treatment prostate inter-surface distance (p < 0.001). Dosimetrically, DOI is negatively correlated with prostate D95 and PTV coverage (p < 0.001). For the model of ERB studied, error in ERB position can cause deformations in the prostate that negatively affect treatment, and this additional aspect of setup error should be considered when ERBs are used for prostate SBRT. Before treatment, the ERB position should be verified, and the ERB should be adjusted if the error is observed to exceed tolerable values.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chi, Y; Rezaeian, N Hassan; Hannan, R

Purpose: Intra-fractional prostate motion leads uncertainty on delivered dose in radiotherapy and may cause significant dose deviation from the planned dose distribution. This is especially a concern in scenarios with a high dose per fraction and hence a long delivery time, e.g. stereotactic body radiotherapy. Knowledge about intra-fractional prostate motion is valuable to address this problem, e.g. by reconstructing delivered dose and performing adaptation. This study proposes a new approach to determine intra-fractional prostate motion in VMAT via 2D/3D maker registration. Methods: At our institution, each patient has three markers implanted in the prostate. During treatment delivery, kV triggered imagesmore » were taken every three seconds to acquire 2D projection of 3D anatomy at the direction orthogonal to the therapeutic beam. Projected marker locations were identified on each projection image using template matching with geometric constraints. 3D prostate translation and rotation for each triggered image were obtained by solving an optimization problem, such that the calculated marker locations match the measured ones. Inter-image motion smoothness was employed as a constraint. We tested this method in simulation studies with five realistic prostate motion trajectories acquired via Calypso and in real phantom experiments. Results: For the simulation case, the motion range for these patients was 0.5∼6.0 mm. Root mean square (RMS) error of calculated motion along left-right (LR), anterior-posterior (AP) and cranial-caudal (CC) directions were 0.26mm, 0.36mm, and 0.016mm, respectively. The motion range in the phantom study along LR, AP, and CC directions were 15mm, 20mm and 10mm. The mean RMS errors along these directions were 1.99mm, 1.37mm and 0.22mm. Conclusion: A new prostate motion tracking algorithm based on kV triggered images has been developed and validated. Clinically acceptable accuracy has been achieved.« less

Analysis of Prostate Patient Setup and Tracking Data: Potential Intervention Strategies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su Zhong, E-mail: zsu@floridaproton.org; Zhang Lisha; Murphy, Martin

Purpose: To evaluate the setup, interfraction, and intrafraction organ motion error distributions and simulate intrafraction intervention strategies for prostate radiotherapy. Methods and Materials: A total of 17 patients underwent treatment setup and were monitored using the Calypso system during radiotherapy. On average, the prostate tracking measurements were performed for 8 min/fraction for 28 fractions for each patient. For both patient couch shift data and intrafraction organ motion data, the systematic and random errors were obtained from the patient population. The planning target volume margins were calculated using the van Herk formula. Two intervention strategies were simulated using the tracking data:more » the deviation threshold and period. The related planning target volume margins, time costs, and prostate position 'fluctuation' were presented. Results: The required treatment margin for the left-right, superoinferior, and anteroposterior axes was 8.4, 10.8, and 14.7 mm for skin mark-only setup and 1.3, 2.3, and 2.8 mm using the on-line setup correction, respectively. Prostate motion significantly correlated among the superoinferior and anteroposterior directions. Of the 17 patients, 14 had prostate motion within 5 mm of the initial setup position for {>=}91.6% of the total tracking time. The treatment margin decreased to 1.1, 1.8, and 2.3 mm with a 3-mm threshold correction and to 0.5, 1.0, and 1.5 mm with an every-2-min correction in the left-right, superoinferior, and anteroposterior directions, respectively. The periodic corrections significantly increase the treatment time and increased the number of instances when the setup correction was made during transient excursions. Conclusions: The residual systematic and random error due to intrafraction prostate motion is small after on-line setup correction. Threshold-based and time-based intervention strategies both reduced the planning target volume margins. The time-based strategies increased the treatment time and the in-fraction position fluctuation.« less

Sci-Thur PM – Brachytherapy 01: Fast brachytherapy dose calculations: Characterization of egs-brachy features to enhance simulation efficiency

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chamberland, Marc; Taylor, Randle E.P.; Rogers, Da

2016-08-15

Purpose: egs-brachy is a fast, new EGSnrc user-code for brachytherapy applications. This study characterizes egs-brachy features that enhance simulation efficiency. Methods: Calculations are performed to characterize efficiency gains from various features. Simulations include radionuclide and miniature x-ray tube sources in water phantoms and idealized prostate, breast, and eye plaque treatments. Features characterized include voxel indexing of sources to reduce boundary checks during radiation transport, scoring collision kerma via tracklength estimator, recycling photons emitted from sources, and using phase space data to initiate simulations. Bremsstrahlung cross section enhancement (BCSE), uniform bremsstrahlung splitting (UBS), and Russian Roulette (RR) are considered for electronicmore » brachytherapy. Results: Efficiency is enhanced by a factor of up to 300 using tracklength versus interaction scoring of collision kerma and by up to 2.7 and 2.6 using phase space sources and particle recycling respectively compared to simulations in which particles are initiated within sources. On a single 2.5 GHz Intel Xeon E5-2680 processor cor, simulations approximating prostate and breast permanent implant ((2 mm){sup 3} voxels) and eye plaque ((1 mm){sup 3}) treatments take as little as 9 s (prostate, eye) and up to 31 s (breast) to achieve 2% statistical uncertainty on doses within the PTV. For electronic brachytherapy, BCSE, UBS, and RR enhance efficiency by a factor >2000 compared to a factor of >10{sup 4} using a phase space source. Conclusion: egs-brachy features provide substantial efficiency gains, resulting in calculation times sufficiently fast for full Monte Carlo simulations for routine brachytherapy treatment planning.« less

Model-based feasibility assessment and evaluation of prostate hyperthermia with a commercial MR-guided endorectal HIFU ablation array

PubMed Central

Salgaonkar, Vasant A.; Prakash, Punit; Rieke, Viola; Ozhinsky, Eugene; Plata, Juan; Kurhanewicz, John; Hsu, I-C. (Joe); Diederich, Chris J.

2014-01-01

Purpose: Feasibility of targeted and volumetric hyperthermia (40–45 °C) delivery to the prostate with a commercial MR-guided endorectal ultrasound phased array system, designed specifically for thermal ablation and approved for ablation trials (ExAblate 2100, Insightec Ltd.), was assessed through computer simulations and tissue-equivalent phantom experiments with the intention of fast clinical translation for targeted hyperthermia in conjunction with radiotherapy and chemotherapy. Methods: The simulations included a 3D finite element method based biothermal model, and acoustic field calculations for the ExAblate ERUS phased array (2.3 MHz, 2.3 × 4.0 cm2, ∼1000 channels) using the rectangular radiator method. Array beamforming strategies were investigated to deliver protracted, continuous-wave hyperthermia to focal prostate cancer targets identified from representative patient cases. Constraints on power densities, sonication durations and switching speeds imposed by ExAblate hardware and software were incorporated in the models. Preliminary experiments included beamformed sonications in tissue mimicking phantoms under MR temperature monitoring at 3 T (GE Discovery MR750W). Results: Acoustic intensities considered during simulation were limited to ensure mild hyperthermia (Tmax < 45 °C) and fail-safe operation of the ExAblate array (spatial and time averaged acoustic intensity ISATA < 3.4 W/cm2). Tissue volumes with therapeutic temperature levels (T > 41 °C) were estimated. Numerical simulations indicated that T > 41 °C was calculated in 13–23 cm3 volumes for sonications with planar or diverging beam patterns at 0.9–1.2 W/cm2, in 4.5–5.8 cm3 volumes for simultaneous multipoint focus beam patterns at ∼0.7 W/cm2, and in ∼6.0 cm3 for curvilinear (cylindrical) beam patterns at 0.75 W/cm2. Focused heating patterns may be practical for treating focal disease in a single posterior quadrant of the prostate and diffused heating patterns may be useful for heating quadrants, hemigland volumes or even bilateral targets. Treatable volumes may be limited by pubic bone heating. Therapeutic temperatures were estimated for a range of physiological parameters, sonication duty cycles and rectal cooling. Hyperthermia specific phasing patterns were implemented on the ExAblate prostate array and continuous-wave sonications (∼0.88 W/cm2, 15 min) were performed in tissue-mimicking material with real-time MR-based temperature imaging (PRFS imaging at 3.0 T). Shapes of heating patterns observed during experiments were consistent with simulations. Conclusions: The ExAblate 2100, designed specifically for thermal ablation, can be controlled for delivering continuous hyperthermia in prostate while working within operational constraints. PMID:24593742

Harmony search optimization for HDR prostate brachytherapy

NASA Astrophysics Data System (ADS)

Panchal, Aditya

In high dose-rate (HDR) prostate brachytherapy, multiple catheters are inserted interstitially into the target volume. The process of treating the prostate involves calculating and determining the best dose distribution to the target and organs-at-risk by means of optimizing the time that the radioactive source dwells at specified positions within the catheters. It is the goal of this work to investigate the use of a new optimization algorithm, known as Harmony Search, in order to optimize dwell times for HDR prostate brachytherapy. The new algorithm was tested on 9 different patients and also compared with the genetic algorithm. Simulations were performed to determine the optimal value of the Harmony Search parameters. Finally, multithreading of the simulation was examined to determine potential benefits. First, a simulation environment was created using the Python programming language and the wxPython graphical interface toolkit, which was necessary to run repeated optimizations. DICOM RT data from Varian BrachyVision was parsed and used to obtain patient anatomy and HDR catheter information. Once the structures were indexed, the volume of each structure was determined and compared to the original volume calculated in BrachyVision for validation. Dose was calculated using the AAPM TG-43 point source model of the GammaMed 192Ir HDR source and was validated against Varian BrachyVision. A DVH-based objective function was created and used for the optimization simulation. Harmony Search and the genetic algorithm were implemented as optimization algorithms for the simulation and were compared against each other. The optimal values for Harmony Search parameters (Harmony Memory Size [HMS], Harmony Memory Considering Rate [HMCR], and Pitch Adjusting Rate [PAR]) were also determined. Lastly, the simulation was modified to use multiple threads of execution in order to achieve faster computational times. Experimental results show that the volume calculation that was implemented in this thesis was within 2% of the values computed by Varian BrachyVision for the prostate, within 3% for the rectum and bladder and 6% for the urethra. The calculation of dose compared to BrachyVision was determined to be different by only 0.38%. Isodose curves were also generated and were found to be similar to BrachyVision. The comparison between Harmony Search and genetic algorithm showed that Harmony Search was over 4 times faster when compared over multiple data sets. The optimal Harmony Memory Size was found to be 5 or lower; the Harmony Memory Considering Rate was determined to be 0.95, and the Pitch Adjusting Rate was found to be 0.9. Ultimately, the effect of multithreading showed that as intensive computations such as optimization and dose calculation are involved, the threads of execution scale with the number of processors, achieving a speed increase proportional to the number of processor cores. In conclusion, this work showed that Harmony Search is a viable alternative to existing algorithms for use in HDR prostate brachytherapy optimization. Coupled with the optimal parameters for the algorithm and a multithreaded simulation, this combination has the capability to significantly decrease the time spent on minimizing optimization problems in the clinic that are time intensive, such as brachytherapy, IMRT and beam angle optimization.

Comparison of Dose Decrement from Intrafraction Motion for Prone and Supine Prostate Radiotherapy

PubMed Central

Olsen, Jeffrey; Parikh, Parag J; Watts, Michael; Noel, Camille E; Baker, Kenneth W; Santanam, Lakshmi; Michalski, Jeff M

2012-01-01

Background and Purpose Dose effects of intrafraction motion during prone prostate radiotherapy are unknown. We compared prone and supine treatment using real-time tracking data to model dose coverage. Material and Methods Electromagnetic tracking data was analyzed for 10 patients treated prone, and 15 treated supine, with IMRT for localized prostate cancer. Plans were generated using 0, 3, and 5 mm PTV expansions. Manual beam-hold interventions were applied to reposition the patient when translations exceeded a predetermined threshold. A custom software application (SWIFTER) used intrafraction tracking data acquired during beam-on to model delivered prostate dose, by applying rigid body transformations to the prostate structure contoured at simulation within the planned dose cloud. The delivered minimum prostate dose as a percentage of planned dose (Dmin%), and prostate volume covered by the prescription dose as a percentage of the planned volume (VRx%) were compared for prone and supine treatment. Results Dmin% was reduced for prone treatment for 0 (p=0.02) and 3 mm (p=0.03) PTV margins. VRx% was reduced for prone treatment only for 0 mm margins (p=0.002). No significant differences were found using 5 mm margins. Conclusions Intrafraction motion has a greater impact on target coverage for prone compared to supine prostate radiotherapy. PTV margins of 3 mm or less correlate with a significant decrease in delivered dose for prone treatment. PMID:22809590

Comparison of dose decrement from intrafraction motion for prone and supine prostate radiotherapy.

PubMed

Olsen, Jeffrey R; Parikh, Parag J; Watts, Michael; Noel, Camille E; Baker, Kenneth W; Santanam, Lakshmi; Michalski, Jeff M

2012-08-01

Dose effects of intrafraction motion during prone prostate radiotherapy are unknown. We compared prone and supine treatment using real-time tracking data to model dose coverage. Electromagnetic tracking data were analyzed for 10 patients treated prone, and 15 treated supine, with IMRT for localized prostate cancer. Plans were generated using 0 mm, 3 mm, and 5mm PTV expansions. Manual beam-hold interventions were applied to reposition the patient when translations exceeded a predetermined threshold. A custom software application (SWIFTER) used intrafraction tracking data acquired during beam-on model delivered prostate dose, by applying rigid body transformations to the prostate structure contoured at simulation within the planned dose cloud. The delivered minimum prostate dose as a percentage of planned dose (Dmin%), and prostate volume covered by the prescription dose as a percentage of the planned volume (VRx%) were compared for prone and supine treatment. Dmin% was reduced for prone treatment for 0 (p=0.02) and 3 mm (p=0.03) PTV margins. VRx% was reduced for prone treatment only for 0mm margins (p=0.002). No significant differences were found using 5 mm margins. Intrafraction motion has a greater impact on target coverage for prone compared to supine prostate radiotherapy. PTV margins of 3 mm or less correlate with a significant decrease in delivered dose for prone treatment. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Cryotherapy simulator for localized prostate cancer.

PubMed

Hahn, James K; Manyak, Michael J; Jin, Ge; Kim, Dongho; Rewcastle, John; Kim, Sunil; Walsh, Raymond J

2002-01-01

Cryotherapy is a treatment modality that uses a technique to selectively freeze tissue and thereby cause controlled tissue destruction. The procedure involves placement of multiple small diameter probes through the perineum into the prostate tissue at selected spatial intervals. Transrectal ultrasound is used to properly position the cylindrical probes before activation of the liquid Argon cooling element, which lowers the tissue temperature below -40 degrees Centigrade. Tissue effect is monitored by transrectal ultrasound changes as well as thermocouples placed in the tissue. The computer-based cryotherapy simulation system mimics the major surgical steps involved in the procedure. The simulated real-time ultrasound display is generated from 3-D ultrasound datasets where the interaction of the ultrasound with the instruments as well as the frozen tissue is simulated by image processing. The thermal and mechanical simulations of the tissue are done using a modified finite-difference/finite-element method optimized for real-time performance. The simulator developed is a part of a comprehensive training program, including a computer-based learning system and hands-on training program with a proctor, designed to familiarize the physician with the technique and equipment involved.

Stereotactic ultrasound for target volume definition in a patient with prostate cancer and bilateral total hip replacement.

PubMed

Boda-Heggemann, Judit; Haneder, Stefan; Ehmann, Michael; Sihono, Dwi Seno Kuncoro; Wertz, Hansjörg; Mai, Sabine; Kegel, Stefan; Heitmann, Sigrun; von Swietochowski, Sandra; Lohr, Frank; Wenz, Frederik

2015-01-01

Target-volume definition for prostate cancer in patients with bilateral metal total hip replacements (THRs) is a challenge because of metal artifacts in the planning computed tomography (CT) scans. Magnetic resonance imaging (MRI) can be used for matching and prostate delineation; however, at a spatial and temporal distance from the planning CT, identical rectal and vesical filling is difficult to achieve. In addition, MRI may also be impaired by metal artifacts, even resulting in spatial image distortion. Here, we present a method to define prostate target volumes based on ultrasound images acquired during CT simulation and online-matched to the CT data set directly at the planning CT. A 78-year-old patient with cT2cNxM0 prostate cancer with bilateral metal THRs was referred to external beam radiation therapy. T2-weighted MRI was performed on the day of the planning CT with preparation according to a protocol for reproducible bladder and rectal filling. The planning CT was obtained with the immediate acquisition of a 3-dimensional ultrasound data set with a dedicated stereotactic ultrasound system for online intermodality image matching referenced to the isocenter by ceiling-mounted infrared cameras. MRI (offline) and ultrasound images (online) were thus both matched to the CT images for planning. Daily image guided radiation therapy (IGRT) was performed with transabdominal ultrasound and compared with cone beam CT. Because of variations in bladder and rectal filling and metal-induced image distortion in MRI, soft-tissue-based matching of the MRI to CT was not sufficient for unequivocal prostate target definition. Ultrasound-based images could be matched, and prostate, seminal vesicles, and target volumes were reliably defined. Daily IGRT could be successfully completed with transabdominal ultrasound with good accordance between cone beam CT and ultrasound. For prostate cancer patients with bilateral THRs causing artifacts in planning CTs, ultrasound referenced to the isocenter of the CT simulator and acquired with intermodal online coregistration directly at the planning CT is a fast and easy method to reliably delineate the prostate and target volumes and for daily IGRT. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Evaluation of the Prostate Bed for Local Recurrence After Radical Prostatectomy Using Endorectal Magnetic Resonance Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.edu; Pitroda, Sean P.; Eggener, Scott E.

Purpose: To summarize the results of a 4-year period in which endorectal magnetic resonance imaging (MRI) was considered for all men referred for salvage radiation therapy (RT) at a single academic center; to describe the incidence and location of locally recurrent disease in a contemporary cohort of men with biochemical failure after radical prostatectomy (RP), and to identify prognostic variables associated with MRI findings in order to define which patients may have the highest yield of the study. Methods and Materials: Between 2007 and 2011, 88 men without clinically palpable disease underwent eMRI for detectable prostate-specific antigen (PSA) after RP.more » The median interval between RP and eMRI was 32 months (interquartile range, 14-57 months), and the median PSA level was 0.30 ng/mL (interquartile range, 0.19-0.72 ng/mL). Magnetic resonance imaging scans consisting of T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging were evaluated for features consistent with local recurrence. The prostate bed was scored from 0-4, whereby 0 was definitely normal, 1 probably normal, 2 indeterminate, 3 probably abnormal, and 4 definitely abnormal. Local recurrence was defined as having a score of 3-4. Results: Local recurrence was identified in 21 men (24%). Abnormalities were best appreciated on T2-weighted axial images (90%) as focal hypointense lesions. Recurrence locations were perianastomotic (67%) or retrovesical (33%). The only risk factor associated with local recurrence was PSA; recurrence was seen in 37% of men with PSA >0.3 ng/mL vs 13% if PSA {<=}0.3 ng/mL (P<.01). The median volume of recurrence was 0.26 cm{sup 3} and was directly associated with PSA (r=0.5, P=.02). The correlation between MRI-based tumor volume and PSA was even stronger in men with positive margins (r=0.8, P<.01). Conclusions: Endorectal MRI can define areas of local recurrence after RP in a minority of men without clinical evidence of disease, with yield related to PSA. Further study is necessary to determine whether eMRI can improve patient selection and success of salvage RT.« less

Value of transrectal power Doppler sonography in the detection of low-risk prostate cancers.

PubMed

Sauvain, J-L; Sauvain, E; Rohmer, P; Louis, D; Nader, N; Papavero, R; Bremon, J-M; Jehl, J

2013-01-01

To evaluate the risk of low-risk prostate cancer or prostate cancer that may benefit from surveillance in patients with a PSA level less than 10 ng/ml, a normal digital rectal examination (DRE) and a transrectal power Doppler sonography (PDS) without anomaly. Two hundred and forty-three consecutive patients with a PSA level less than 10 ng/ml and a DRE without anomaly had PDS-guided biopsies: 12 to 15 samples were systematically taken and echo-guided in the suspect areas. The PDS results were rated from 1 to 4: 1: normal, 2: slightly hypoechogenic avascular area in which the hypo-echogenicity disappears after compression by probe, 3: hypoechogenic avascular area, 4: hypoechogenic vascularised area with power Doppler sonography. Patients rated 3 or 4 were considered to be pathological. D'Amico's criteria were used to assess the risk of a biological recurrence after treatment and those of Dall'Era were used to select the patients that could benefit from active surveillance (AS). The PDS was considered to be a true positive if at least one biopsy was positive in the same sextant as the suspect image. In a prospective manner, 106 cancers were diagnosed that could be qualified as low-risk in 84% of the cases (89% with a normal PDS and 79% with an abnormal PDS). Sixty-nine percent of the cases could be subject to AS (86% of the normal PDS cases and 47% of the abnormal PDS cases; P<0.001). The PDS was normal in 159 of the 243 patients (65%). With a normal PDS, there was a 96% probability of not having a high-risk cancer. With an abnormal PDS, at least one biopsy was positive in 57% of the cases and the probability of having a significant cancer was 30% according to the Dall'Era criteria. A significant reduction was noted with a normal PDS, to 36% and 5%, respectively (VPN=95%) (P=0.015). A normal PDS in patients presenting a PSA level less than 10 ng/ml and a DRE without anomaly may be used to put off the indication for a biopsy in order to reduce their number as well as the risks of overtreatment for a latent cancer. Copyright © 2012 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Motion correction for radiation therapy of prostate using B-mode ultrasound

NASA Astrophysics Data System (ADS)

Hummel, Johann; Figl, Michael; Schmidbauer, Jörg; Tinzl, Martina; Bergmann, Helmar; Birkfellner, Wolfgang

2007-03-01

The use of intensity modulated radiation therapy promises to spare organs at risk by applying better dose distribution on the tumor. The specific challenge of this methods is the exact positioning of the patient and the localization of the exposured organ. With respect to the filling of rectum and bladder the prostate can move several millimeters up to centimeters. Therefore, the position of the prostate should be determinated and corrected daily before irradiation. We used a B-mode US machine (Ultramark 9, advanced Technology Laboratories, USA) which was calibrated using an optical tracking system (Polaris, NDI, Can). After correct positioning of the patient in the simulation room three anatomical markers (apex prostate, prostate lateral sinister/dexter) were identified and their positions calculated with respect to the coordinate system of the simulator. The same situation is given in the treatment room. Both, simulator and accelerator are registered by a simple point-to-point registration using a block with five drilled holes with known coordinates in the block coordinate system. The block is aligned by means of laser markers. When the patient is placed on the treatment table, the three anatomical landmarks are located on the US images and their positions are calculated with respect to the coordinate system of the treatment room. Applying a point-to-point registration results in a rotation matrix and a translation vector in the desired coordinate system which can be used for repositioning by translating and rotating the patient table. Additionally, a fiducial registration error (FRE) is calculated which gives a dimension of the accuracy the three points were identified. We found an fiducial registration error (FRE) of 2.4 mm +/- 1.2 mm for the point-to-point registration of the anatomical landmarks. The FRE for the point-to-point registration between the block and the optical tracking system was 0.5 mm +/- 0.2 mm. According to the US calibration we found an error of 0.8 mm +/- 0.2 mm.

Effect of Gold Nanoparticles on Prostate Dose Distribution under Ir-192 Internal and 18 MV External Radiotherapy Procedures Using Gel Dosimetry and Monte Carlo Method.

PubMed

Khosravi, H; Hashemi, B; Mahdavi, S R; Hejazi, P

2015-03-01

Gel polymers are considered as new dosimeters for determining radiotherapy dose distribution in three dimensions. The ability of a new formulation of MAGIC-f polymer gel was assessed by experimental measurement and Monte Carlo (MC) method for studying the effect of gold nanoparticles (GNPs) in prostate dose distributions under the internal Ir-192 and external 18MV radiotherapy practices. A Plexiglas phantom was made representing human pelvis. The GNP shaving 15 nm in diameter and 0.1 mM concentration were synthesized using chemical reduction method. Then, a new formulation of MAGIC-f gel was synthesized. The fabricated gel was poured in the tubes located at the prostate (with and without the GNPs) and bladder locations of the phantom. The phantom was irradiated to an Ir-192 source and 18 MV beam of a Varian linac separately based on common radiotherapy procedures used for prostate cancer. After 24 hours, the irradiated gels were read using a Siemens 1.5 Tesla MRI scanner. The absolute doses at the reference points and isodose curves resulted from the experimental measurement of the gels and MC simulations following the internal and external radiotherapy practices were compared. The mean absorbed doses measured with the gel in the presence of the GNPs in prostate were 15% and 8 % higher than the corresponding values without the GNPs under the internal and external radiation therapies, respectively. MC simulations also indicated a dose increase of 14 % and 7 % due to presence of the GNPs, for the same experimental internal and external radiotherapy practices, respectively. There was a good agreement between the dose enhancement factors (DEFs) estimated with MC simulations and experiment gel measurements due to the GNPs. The results indicated that the polymer gel dosimetry method as developed and used in this study, can be recommended as a reliable method for investigating the DEF of GNPs in internal and external radiotherapy practices.

Intrafraction Prostate Translations and Rotations During Hypofractionated Robotic Radiation Surgery: Dosimetric Impact of Correction Strategies and Margins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Water, Steven van de, E-mail: s.vandewater@erasmusmc.nl; Valli, Lorella; Alma Mater Studiorum, Department of Physics and Astronomy, Bologna University, Bologna

Purpose: To investigate the dosimetric impact of intrafraction prostate motion and the effect of robot correction strategies for hypofractionated CyberKnife treatments with a simultaneously integrated boost. Methods and Materials: A total of 548 real-time prostate motion tracks from 17 patients were available for dosimetric simulations of CyberKnife treatments, in which various correction strategies were included. Fixed time intervals between imaging/correction (15, 60, 180, and 360 seconds) were simulated, as well as adaptive timing (ie, the time interval reduced from 60 to 15 seconds in case prostate motion exceeded 3 mm or 2° in consecutive images). The simulated extent of robot corrections was alsomore » varied: no corrections, translational corrections only, and translational corrections combined with rotational corrections up to 5°, 10°, and perfect rotational correction. The correction strategies were evaluated for treatment plans with a 0-mm or 3-mm margin around the clinical target volume (CTV). We recorded CTV coverage (V{sub 100%}) and dose-volume parameters of the peripheral zone (boost), rectum, bladder, and urethra. Results: Planned dose parameters were increasingly preserved with larger extents of robot corrections. A time interval between corrections of 60 to 180 seconds provided optimal preservation of CTV coverage. To achieve 98% CTV coverage in 98% of the treatments, translational and rotational corrections up to 10° were required for the 0-mm margin plans, whereas translational and rotational corrections up to 5° were required for the 3-mm margin plans. Rectum and bladder were spared considerably better in the 0-mm margin plans. Adaptive timing did not improve delivered dose. Conclusions: Intrafraction prostate motion substantially affected the delivered dose but was compensated for effectively by robot corrections using a time interval of 60 to 180 seconds. A 0-mm margin required larger extents of additional rotational corrections than a 3-mm margin but resulted in lower doses to rectum and bladder.« less

Colour Doppler and microbubble contrast agent ultrasonography do not improve cancer detection rate in transrectal systematic prostate biopsy sampling.

PubMed

Taverna, Gianluigi; Morandi, Giovanni; Seveso, Mauro; Giusti, Guido; Benetti, Alessio; Colombo, Piergiuseppe; Minuti, Francesco; Grizzi, Fabio; Graziotti, Pierpaolo

2011-12-01

What's known on the subject? and What does the study add? Transrectal gray-scale ultrasonography guided prostate biopsy sampling is the method for diagnosing prostate cancer (PC) in patients with an increased prostate specific antigen level and/or abnormal digital rectal examination. Several imaging strategies have been proposed to optimize the diagnostic value of biopsy sampling, although at the first biopsy nearly 10-30% of PC still remains undiagnosed. This study compares the PC detection rate when employing Colour Doppler ultransongraphy with or without the injection of SonoVue™ microbubble contrast agent, versus the transrectal ultrasongraphy-guided systematic biopsy sampling. The limited accuracy, sensitivity, specificity and the additional cost of using the contrast agent do not justify its routine application in PC detection. • To compare prostate cancer (PC) detection rate employing colour Doppler ultrasonography with or without SonoVue™ contrast agent with transrectal ultrasonography-guided systematic biopsy sampling. • A total of 300 patients with negative digital rectal examination and transrectal grey-scale ultrasonography, with PSA values ranging between 2.5 and 9.9 ng/mL, were randomized into three groups: 100 patients (group A) underwent transrectal ultrasonography-guided systematic bioptic sampling; 100 patients (group B) underwent colour Doppler ultrasonography, and 100 patients (group C) underwent colour Doppler ultrasonography before and during the injection of SonoVue™. • Contrast-enhanced targeted biopsies were sampled into hypervascularized areas of peripheral, transitional, apical or anterior prostate zones. • All the patients included in Groups B and C underwent a further 13 systematic prostate biopsies. The cancer detection rate was calculated for each group. • In 88 (29.3%) patients a histological diagnosis of PC was made, whereas 22 (7.4%) patients were diagnosed with high-grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. • No significant differences were found among the three groups for cancer detection rate (P= 0.329). • Additionally, low sensitivity, specificity and accuracy of colour Doppler with or without SonoVue™ contrast agent were found. • Prostate cancer detection rate does not significantly improve with the use of colour Doppler ultrasonography with or without SonoVue™. • Although no collateral effects have been highlighted, the combined use of colour Doppler ultrasonography and SonoVue™ determines adjunctive costs and increases the mean time for taking a single prostate biopsy. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

Modeling of Radiotherapy Linac Source Terms Using ARCHER Monte Carlo Code: Performance Comparison for GPU and MIC Parallel Computing Devices

NASA Astrophysics Data System (ADS)

Lin, Hui; Liu, Tianyu; Su, Lin; Bednarz, Bryan; Caracappa, Peter; Xu, X. George

2017-09-01

Monte Carlo (MC) simulation is well recognized as the most accurate method for radiation dose calculations. For radiotherapy applications, accurate modelling of the source term, i.e. the clinical linear accelerator is critical to the simulation. The purpose of this paper is to perform source modelling and examine the accuracy and performance of the models on Intel Many Integrated Core coprocessors (aka Xeon Phi) and Nvidia GPU using ARCHER and explore the potential optimization methods. Phase Space-based source modelling for has been implemented. Good agreements were found in a tomotherapy prostate patient case and a TrueBeam breast case. From the aspect of performance, the whole simulation for prostate plan and breast plan cost about 173s and 73s with 1% statistical error.

Molecular Targeting of Prostate Cancer During Androgen Ablation: Inhibition of CHES1/FOXN3

DTIC Science & Technology

2013-05-01

the DNA sequences (~25^6 reads/sample) were mapped to the human genome reference sequence (hg19...tumor the AR has a genomic abnormality, placing the novel sequence 3’ of the transcriptional start site. However, it is unclear if a genomic alteration...exon/intron organization of the CHES1 gene was determined by BLAST analysis of the human genome using the 1,473-bp CHES1 cDNA sequence

Role of p53 in cdk Inhibitor VMY-1-103-Induced Apoptosis in Prostate Cancer

DTIC Science & Technology

2012-09-01

trioxide inhibits human cancer cell growth and tumor development in mice by blocking Hedgehog /GLI pathway. J Clin Invest. 2011 Jan 4;121(1):148- 60...subclassified the tumors based on gene expression patterns and chromosomal abnormalities.4-6 Dysregulation of Hedgehog (Hh) signaling, defined as the c3...Eberhart CG. Hedgehog signaling promotes medulloblastoma survival via Bc/II. Am J Pathol 2007; 170:347-55; PMID:17200206; DOI:10.2353/ajpath

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

PubMed Central

Acampora, Giovanni; Brown, David; Rees, Robert C.

2016-01-01

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 = 0.032, TPR = 0.197, AUC = 0.582). PMID:27258119

Diethylstilbesterol revisited: androgen deprivation, osteoporosis and prostate cancer.

PubMed

Scherr, Douglas; Pitts, W Reid; Vaughn, E Darracott

2002-02-01

It is well described in the urological literature that androgen deprivation can result in accelerated bone breakdown and osteoporosis. Therefore, we evaluate the degree of bone breakdown in patients on conventional androgen deprivation with those on diethylstilbesterol alone or in conjunction with luteinizing hormone releasing hormone agonists or orchiectomy. During an 18-month period a total of 54 patients with clinically localized prostate cancer and 24 with benign prostatic hyperplasia were evaluated. All patients with prostate cancer were either treated with external beam radiotherapy without androgen deprivation or were started on androgen deprivation therapy. All patients were prospectively followed and evaluated for serum testosterone and estradiol along with urinary collagen type I cross-linked N-telopeptides. Three separate morning urine samples on 3 separate months were collected on each patient and analyzed for N-telopeptides. To correct for different levels of renal function, all N-telopeptides were measured as a ratio of urinary N-telopeptides/urine creatinine. All patients with any bone or skeletal abnormalities were excluded from study as were those with osseous metastatic disease. There was a statistically significant (p < 0.05) higher level of urinary N-telopeptides/creatinine in patients on androgen deprivation therapy who were not treated with diethylstilbesterol. The estrogenic effect of diethylstilbesterol protects one from bone resorption. Patients on diethylstilbesterol did not have any higher levels of bone breakdown than patients with benign prostatic hyperplasia or those who never received any androgen deprivation. Rapid bone turnover and resorption can be prevented with 1 mg. diethylstilbesterol alone or in conjunction with other modes of androgen deprivation. Therefore, diethylstilbesterol should be considered as monotherpy in men who require long-term antiandrogen therapy.

A three-gene panel on urine increases PSA specificity in the detection of prostate cancer.

PubMed

Rigau, Marina; Ortega, Israel; Mir, Maria Carmen; Ballesteros, Carlos; Garcia, Marta; Llauradó, Marta; Colás, Eva; Pedrola, Núria; Montes, Melania; Sequeiros, Tamara; Ertekin, Tugce; Majem, Blanca; Planas, Jacques; Ruiz, Anna; Abal, Miguel; Sánchez, Alex; Morote, Juan; Reventós, Jaume; Doll, Andreas

2011-12-01

Several studies have demonstrated the usefulness of monitoring an RNA transcript, such as PCA3, in post-prostate massage (PM) urine for increasing the specificity of prostate-specific antigen (PSA) in the detection of prostate cancer (PCa). However, a single marker may not necessarily reflect the multifactorial nature of PCa. We analyzed post-PM urine samples from 154 consecutive patients, who presented for prostate biopsies because of elevated serum PSA (>4 ng/ml) and/or abnormal digital rectal exam. We tested whether the putative PCa biomarkers PSMA, PSGR, and PCA3 could be detected by quantitative real-time PCR in post-PM urine sediment. We combined these findings to test if a combination of these biomarkers could improve the specificity of actual diagnosis. Afterwards, we specifically tested our model for clinical usefulness in the PSA diagnostic "gray zone" (4-10 ng/ml) on a target subset of 82 men with no prior biopsy. By univariate analysis, we found that the PSMA, PSGR, and PCA3 scores were significant predictors of PCa. Using a multiplex model, the area under the multi receiver-operating characteristic curve was 0.74 versus 0.82 in the diagnostic "gray zone." Fixing the sensitivity at 96%, we obtained a specificity of 34% and 50% in the gray zone. Taken together, these results provide a strategy for the development of a more accurate model for PCa diagnosis. In the future, a multiplexed, urine-based diagnostic test for PCa with a higher specificity, but the same sensitivity as the serum-PSA test, could be used to determine better which patients should undergo biopsy. Copyright © 2011 Wiley Periodicals, Inc.

The use of morphological characteristics and texture analysis in the identification of tissue composition in prostatic neoplasia.

PubMed

Diamond, James; Anderson, Neil H; Bartels, Peter H; Montironi, Rodolfo; Hamilton, Peter W

2004-09-01

Quantitative examination of prostate histology offers clues in the diagnostic classification of lesions and in the prediction of response to treatment and prognosis. To facilitate the collection of quantitative data, the development of machine vision systems is necessary. This study explored the use of imaging for identifying tissue abnormalities in prostate histology. Medium-power histological scenes were recorded from whole-mount radical prostatectomy sections at x 40 objective magnification and assessed by a pathologist as exhibiting stroma, normal tissue (nonneoplastic epithelial component), or prostatic carcinoma (PCa). A machine vision system was developed that divided the scenes into subregions of 100 x 100 pixels and subjected each to image-processing techniques. Analysis of morphological characteristics allowed the identification of normal tissue. Analysis of image texture demonstrated that Haralick feature 4 was the most suitable for discriminating stroma from PCa. Using these morphological and texture measurements, it was possible to define a classification scheme for each subregion. The machine vision system is designed to integrate these classification rules and generate digital maps of tissue composition from the classification of subregions; 79.3% of subregions were correctly classified. Established classification rates have demonstrated the validity of the methodology on small scenes; a logical extension was to apply the methodology to whole slide images via scanning technology. The machine vision system is capable of classifying these images. The machine vision system developed in this project facilitates the exploration of morphological and texture characteristics in quantifying tissue composition. It also illustrates the potential of quantitative methods to provide highly discriminatory information in the automated identification of prostatic lesions using computer vision.

A two-week, double-blind, placebo-controlled trial of Viola odorata, Echium amoenum and Physalis alkekengi mixture in symptomatic benign prostate hyperplasia (BPH) men.

PubMed

Beiraghdar, Fatemeh; Einollahi, Behzad; Ghadyani, Alireza; Panahi, Yunes; Hadjiakhoondi, Abbas; Vazirian, Mahdi; Salarytabar, Ali; Darvishi, Behrad

2017-12-01

As an alternative approach, administration of phytotherapeutic agents in management of benign prostate hyperplasia (BPH), is rapidly growing each day. Different authors have indicated effectiveness of Viola odorata L. (Violaceae), Echium amoenum Fisch. & C.A.Mey. (Boraginaceae) and Physalis alkekengi L. (Solanaceae) in treatment of BPH. However, none have reported the beneficial outcomes of the mixture yet. This study evaluates the therapeutical effects of V. odorata, E. amoenum and P. alkekengi mixture on symptomatic BPH patients. Eighty six symptomatic BPH patients with International Prostate Symptom Score (IPSS) of more than 13 and prostate volume of more than 30 cm 3 were randomly allocated to receive a two-week course of placebo (control group) or 1 mL of mixed hydro-alcoholic solution of P. alkekengi, E. amoenum and V. odorata extracts (1.5, 1 and 1.5% respectively) (treatment group). IPSS score of incomplete urination (42.3 ± 2.04%), frequency of urination (20.08 ± 1.02%), intermittency (40.78 ± 2.16%), urgency (60.91 ± 3.14%), weak stream (50.58 ± 2.14%), straining (55.67 ± 2.53%) and nocturia (40.14 ± 1.89%) in treatment group were significantly decreased after treatment compare to placebo receiving group. Furthermore, the prostate volume (16.92 ± 0.89%) and extant urine volume (28.12 ± 1.36%) also significantly decreased in treatment group compared to control group. No significant side effects or abnormalities in biochemical tests and urinalysis were observed throughout the study. Based on results, mentioned mixture is safe and effective in improving life quality of patients suffering from BPH.

Cell membrane water exchange effects in prostate DCE-MRI

NASA Astrophysics Data System (ADS)

Li, Xin; Priest, Ryan A.; Woodward, William J.; Siddiqui, Faisal; Beer, Tomasz M.; Garzotto, Mark G.; Rooney, William D.; Springer, Charles S.

2012-05-01

Prostate Dynamic-Contrast-Enhanced (DCE) MRI often exhibits fast and extensive global contrast reagent (CR) extravasation - measured by Ktrans, a pharmacokinetic parameter proportional to its rate. This implies that the CR concentration [CR] is high in the extracellular, extravascular space (EES) during a large portion of the DCE-MRI study. Since CR is detected indirectly, through water proton signal change, the effects of equilibrium transcytolemmal water exchange may be significant in the data and thus should be admitted in DCE-MRI pharmacokinetic modeling. The implications for parameter values were investigated through simulations, and analyses of actual prostate data, with different models. Model parameter correlation and precision were also explored. A near-optimal version of the exchange-sensitized model was found. Our results indicate that ΔKtrans (the Ktrans difference returned by this version and a model assuming exchange to be effectively infinitely fast) may be a very useful biomarker for discriminating malignant from benign prostate tissue. Using an exchange-sensitized model, we find that the mean intracellular water lifetime (τi) - an exchange measure - can be meaningfully mapped for the prostate. Our results show prostate glandular zone differences in τi values.

Pilot Comparison of ⁶⁸Ga-RM2 PET and ⁶⁸Ga-PSMA-11 PET in Patients with Biochemically Recurrent Prostate Cancer.

PubMed

Minamimoto, Ryogo; Hancock, Steven; Schneider, Bernadette; Chin, Frederick T; Jamali, Mehran; Loening, Andreas; Vasanawala, Shreyas; Gambhir, Sanjiv Sam; Iagaru, Andrei

2016-04-01

Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga(HBED-CC)] ((68)Ga-PSMA-11) is a PET tracer that can detect prostate cancer relapses and metastases by binding to the extracellular domain of PSMA. (68)Ga-labeled DOTA-4-amino-1-carboxymethyl-piperidine-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 ((68)Ga-RM2) is a synthetic bombesin receptor antagonist that targets gastrin-releasing peptide receptors. We present pilot data on the biodistribution of these PET tracers in a small cohort of patients with biochemically recurrent prostate cancer. Seven men (mean age ± SD, 74.3 ± 5.9 y) with biochemically recurrent prostate cancer underwent both (68)Ga-PSMA-11 PET/CT and (68)Ga-RM2 PET/MRI scans. SUVmax and SUVmean were recorded for normal tissues and areas of uptake outside the expected physiologic biodistribution. All patients had a rising level of prostate-specific antigen (mean ± SD, 13.5 ± 11.5) and noncontributory results on conventional imaging. (68)Ga-PSMA-11 had the highest physiologic uptake in the salivary glands and small bowel, with hepatobiliary and renal clearance noted, whereas (68)Ga-RM2 had the highest physiologic uptake in the pancreas, with renal clearance noted. Uptake outside the expected physiologic biodistribution did not significantly differ between (68)Ga-PSMA-11 and (68)Ga-RM2; however, (68)Ga-PSMA-11 localized in a lymph node and seminal vesicle in a patient with no abnormal (68)Ga-RM2 uptake. Abdominal periaortic lymph nodes were more easily visualized by(68)Ga-RM2 in two patients because of lack of interference by radioactivity in the small intestine. (68)Ga-PSMA-11 and (68)Ga-RM2 had distinct biodistributions in this small cohort of patients with biochemically recurrent prostate cancer. Additional work is needed to understand the expression of PSMA and gastrin-releasing peptide receptors in different types of prostate cancer. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Methods for prostate stabilization during transperineal LDR brachytherapy.

PubMed

Podder, Tarun; Sherman, Jason; Rubens, Deborah; Messing, Edward; Strang, John; Ng, Wan-Sing; Yu, Yan

2008-03-21

In traditional prostate brachytherapy procedures for a low-dose-rate (LDR) radiation seed implant, stabilizing needles are first inserted to provide some rigidity and support to the prostate. Ideally this will provide better seed placement and an overall improved treatment. However, there is much speculation regarding the effectiveness of using regular brachytherapy needles as stabilizers. In this study, we explored the efficacy of two types of needle geometries (regular brachytherapy needle and hooked needle) and several clinically feasible configurations of the stabilization needles. To understand and assess the prostate movement during seed implantation, we collected in vivo data from patients during actual brachytherapy procedures. In vitro experimentation with tissue-equivalent phantoms allowed us to further understand the mechanics behind prostate stabilization. We observed superior stabilization with the hooked needles compared to the regular brachytherapy needles (more than 40% in bilateral parallel needle configuration). Prostate movement was also reduced significantly when regular brachytherapy needles were in an angulated configuration as compared to the parallel configuration (more than 60%). When the hooked needles were angulated for stabilization, further reduction in prostate displacement was observed. In general, for convenience of dosimetric planning and to avoid needle collision, all needles are desired to be in a parallel configuration. In this configuration, hooked needles provide improved stabilization of the prostate. On the other hand, both regular and hooked needles appear to be equally effective in reducing prostate movement when they are in angulated configurations, which will be useful in seed implantation using a robotic system. We have developed nonlinear spring-damper model for the prostate movement which can be used for adapting dosimetric planning during brachytherapy as well as for developing more realistic haptic devices and training simulators.

WE-A-17A-11: Implanted Brachytherapy Seed Movement Due to Transrectal Ultrasound Probe-Induced Prostate Deformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, D; Usmani, N; Sloboda, R

Purpose: To characterize the movement of implanted brachytherapy seeds due to transrectal ultrasound probe-induced prostate deformation and to estimate the effects on prostate dosimetry. Methods: Implanted probe-in and probe-removed seed distributions were reconstructed for 10 patients using C-arm fluoroscopy imaging. The prostate was delineated on ultrasound and registered to the fluoroscopy seeds using a visible subset of seeds and residual needle tracks. A linear tensor and shearing model correlated the seed movement with position. The seed movement model was used to infer the underlying prostate deformation and to simulate the prostate contour without probe compression. Changes in prostate and surrogatemore » urethra dosimetry were calculated. Results: Seed movement patterns reflecting elastic decompression, lateral shearing, and rectal bending were observed. Elastic decompression was characterized by anterior-posterior expansion and superior-inferior and lateral contractions. For lateral shearing, anterior movement up to 6 mm was observed for extraprostatic seeds in the lateral peripheral region. The average intra-prostatic seed movement was 1.3 mm, and the residual after linear modeling was 0.6 mm. Prostate D90 increased by 4 Gy on average (8 Gy max) and was correlated with elastic decompression. For selected patients, lateral shearing resulted in differential change in D90 of 7 Gy between anterior and posterior quadrants, and increase in whole prostate D90 of 4 Gy. Urethra D10 increased by 4 Gy. Conclusion: Seed movement upon probe removal was characterized. The proposed model captured the linear correlation between seed movement and position. Whole prostate dose coverage increased slightly, due to the small but systematic seed movement associated with elastic decompression. Lateral shearing movement increased dose coverage in the anterior-lateral region, at the expense of the posterior-lateral region. The effect on whole prostate D90 was smaller due to the subset of peripheral seeds involved, but lateral shearing movement can have greater consequences for local dose coverage.« less

A Multiscale, Mechanism-Driven, Dynamic Model for the Effects of 5α-Reductase Inhibition on Prostate Maintenance

PubMed Central

Zager, Michael G.; Barton, Hugh A.

2012-01-01

A systems-level mathematical model is presented that describes the effects of inhibiting the enzyme 5α-reductase (5aR) on the ventral prostate of the adult male rat under chronic administration of the 5aR inhibitor, finasteride. 5aR is essential for androgen regulation in males, both in normal conditions and disease states. The hormone kinetics and downstream effects on reproductive organs associated with perturbing androgen regulation are complex and not necessarily intuitive. Inhibition of 5aR decreases the metabolism of testosterone (T) to the potent androgen 5α-dihydrotestosterone (DHT). This results in decreased cell proliferation, fluid production and 5aR expression as well as increased apoptosis in the ventral prostate. These regulatory changes collectively result in decreased prostate size and function, which can be beneficial to men suffering from benign prostatic hyperplasia (BPH) and could play a role in prostate cancer. There are two distinct isoforms of 5aR in male humans and rats, and thus developing a 5aR inhibitor is a challenging pursuit. Several inhibitors are on the market for treatment of BPH, including finasteride and dutasteride. In this effort, comparisons of simulated vs. experimental T and DHT levels and prostate size are depicted, demonstrating the model accurately described an approximate 77% decrease in prostate size and nearly complete depletion of prostatic DHT following 21 days of daily finasteride dosing in rats. This implies T alone is not capable of maintaining a normal prostate size. Further model analysis suggests the possibility of alternative dosing strategies resulting in similar or greater effects on prostate size, due to complex kinetics between T, DHT and gene occupancy. With appropriate scaling and parameterization for humans, this model provides a multiscale modeling platform for drug discovery teams to test and generate hypotheses about drugging strategies for indications like BPH and prostate cancer, such as compound binding properties, dosing regimens, and target validation. PMID:22970204

Feeling Abnormal: Simulation of Deviancy in Abnormal and Exceptionality Courses.

ERIC Educational Resources Information Center

Fernald, Charles D.

1980-01-01

Describes activity in which student in abnormal psychology and psychology of exceptional children classes personally experience being judged abnormal. The experience allows the students to remember relevant research, become sensitized to the feelings of individuals classified as deviant, and use caution in classifying individuals as abnormal.…

High-resolution 3D MR spectroscopic imaging of the prostate at 3 T with the MLEV-PRESS sequence.

PubMed

Chen, Albert P; Cunningham, Charles H; Kurhanewicz, John; Xu, Duan; Hurd, Ralph E; Pauly, John M; Carvajal, Lucas; Karpodinis, Kostas; Vigneron, Daniel B

2006-09-01

A 3 T MLEV-point-resolved spectroscopy (PRESS) sequence employing optimized spectral-spatial and very selective outer-voxel suppression pulses was tested in 25 prostate cancer patients. At an echo time of 85 ms, the MLEV-PRESS sequence resulted in maximally upright inner resonances and minimal outer resonances of the citrate doublet of doublets. Magnetic resonance spectroscopic imaging (MRSI) exams performed at both 3 and 1.5 T for 10 patients demonstrated a 2.08+/-0.36-fold increase in signal-to-noise ratio (SNR) at 3 T as compared with 1.5 T for the center citrate resonances. This permitted the acquisition of MRSI data with a nominal spatial resolution of 0.16 cm3 at 3 T with similar SNR as the 0.34-cm3 data acquired at 1.5 T. Due to the twofold increase in spectral resolution at 3 T and the improved magnetic field homogeneity provided by susceptibility-matched endorectal coils, the choline resonance was better resolved from polyamine and creatine resonances as compared with 1.5 T spectra. In prostate cancer patients, the elevation of choline and the reduction of polyamines were more clearly observed at 3 T, as compared with 1.5 T MRSI. The increased SNR and corresponding spatial resolution obtainable at 3 T reduced partial volume effects and allowed improved detection of the presence and extent of abnormal metabolite levels in prostate cancer patients, as compared with 1.5 T MRSI.

Safety and efficacy of silodosin for the treatment of benign prostatic hyperplasia

PubMed Central

Yoshida, Masaki; Kudoh, Junzo; Homma, Yukio; Kawabe, Kazuki

2011-01-01

Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are highly prevalent in older men. Medical therapy is the first-line treatment for LUTS associated with BPH. Mainstays in the treatment of male LUTS and clinical BPH are the α1-adrenergic receptor antagonists. Silodosin is a new α1-adrenergic receptor antagonist that is selective for the α1A-adrenergic receptor. By antagonizing α1A-adrenergic receptors in the prostate and urethra, silodosin causes smooth muscle relaxation in the lower urinary tract. Since silodosin has greater affinity for the α1A-adrenergic receptor than for the α1B-adrenergic receptor, it minimizes the propensity for blood pressure-related adverse effects caused by α1B-adrenergic receptor blockade. In the clinical studies, patients receiving silodosin at a total daily dose of 8 mg exhibited significant improvements in the International Prostate Symptom Score and maximum urinary flow rate compared with those receiving placebo. Silodosin showed early onset of efficacy for both voiding and storage symptoms. Furthermore, long-term safety of silodosin was also demonstrated. Retrograde or abnormal ejaculation was the most commonly reported adverse effect. The incidence of orthostatic hypotension was low. In conclusion, silodosin, a novel selective α1A-adrenergic receptor antagonist, was effective in general and without obtrusive side effects. This review provides clear evidence in support of the clinical usefulness of silodosin in the treatment of LUTS associated with BPH. PMID:21753871

Medical malpractice of prostate brachytherapy.

PubMed

Elliott, Kathryn; Wallner, Kent; Merrick, Gregory; Herstein, Paul

2004-01-01

To summarize the basis for brachytherapy-associated legal complaints. The cases summarized here were those worked on by one author (KW) from 1992 through 2002. Summary information about cases is kept solely for the purpose of informing opposing counsel regarding past experience as a defendant or expert witness. No information summarized here is kept for medical research purposes. KW was the defendant in three cases, and an expert witness in the remaining 10 cases. Eleven cases were initiated due to a prostatic-rectal fistula--an abnormal communication between the prostatic urethra and rectum formed because of breakdown of irradiated tissue. Of the cases not involving a fistula, one was initiated due to chronic urinary burning, and the other arose from a patient identification mix-up, such that the plaintiff was treated with the implant planned for another patient. The principal physician defendant(s), after pre-trial winnowing, was the radiation oncologist alone in eight cases and the radiation oncologist and the urologist in five cases. In no case was a urologist named as a defendant without the radiation oncologist. None of the eleven rectal fistula cases involved an egregious seed placement error. Instead, plaintiff attorneys typically claimed breach of standard for care for what most physicians would likely consider to be variations within the standard of care. Prostate brachytherapists should brace themselves for the likelihood of more lawsuits. In addition to fistulas, plaintiff attorneys are likely to devise more bases for lawsuits in the future.

Simulation of pseudo-CT images based on deformable image registration of ultrasound images: A proof of concept for transabdominal ultrasound imaging of the prostate during radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meer, Skadi van der; Camps, Saskia M.; Oncology Solutions Department, Philips Research, High Tech Campus 34, Eindhoven 5656 AE

Purpose: Imaging of patient anatomy during treatment is a necessity for position verification and for adaptive radiotherapy based on daily dose recalculation. Ultrasound (US) image guided radiotherapy systems are currently available to collect US images at the simulation stage (US{sub sim}), coregistered with the simulation computed tomography (CT), and during all treatment fractions. The authors hypothesize that a deformation field derived from US-based deformable image registration can be used to create a daily pseudo-CT (CT{sub ps}) image that is more representative of the patients’ geometry during treatment than the CT acquired at simulation stage (CT{sub sim}). Methods: The three prostatemore » patients, considered to evaluate this hypothesis, had coregistered CT and US scans on various days. In particular, two patients had two US–CT datasets each and the third one had five US–CT datasets. Deformation fields were computed between pairs of US images of the same patient and then applied to the corresponding US{sub sim} scan to yield a new deformed CT{sub ps} scan. The original treatment plans were used to recalculate dose distributions in the simulation, deformed and ground truth CT (CT{sub gt}) images to compare dice similarity coefficients, maximum absolute distance, and mean absolute distance on CT delineations and gamma index (γ) evaluations on both the Hounsfield units (HUs) and the dose. Results: In the majority, deformation did improve the results for all three evaluation methods. The change in gamma failure for dose (γ{sub Dose}, 3%, 3 mm) ranged from an improvement of 11.2% in the prostate volume to a deterioration of 1.3% in the prostate and bladder. The change in gamma failure for the CT images (γ{sub CT}, 50 HU, 3 mm) ranged from an improvement of 20.5% in the anus and rectum to a deterioration of 3.2% in the prostate. Conclusions: This new technique may generate CT{sub ps} images that are more representative of the actual patient anatomy than the CT{sub sim} scan.« less

MR thermometry characterization of a hyperthermia ultrasound array designed using the k-space computational method

PubMed Central

Al-Bataineh, Osama M; Collins, Christopher M; Park, Eun-Joo; Lee, Hotaik; Smith, Nadine Barrie

2006-01-01

Background Ultrasound induced hyperthermia is a useful adjuvant to radiation therapy in the treatment of prostate cancer. A uniform thermal dose (43°C for 30 minutes) is required within the targeted cancerous volume for effective therapy. This requires specific ultrasound phased array design and appropriate thermometry method. Inhomogeneous, acoustical, three-dimensional (3D) prostate models and economical computational methods provide necessary tools to predict the appropriate shape of hyperthermia phased arrays for better focusing. This research utilizes the k-space computational method and a 3D human prostate model to design an intracavitary ultrasound probe for hyperthermia treatment of prostate cancer. Evaluation of the probe includes ex vivo and in vivo controlled hyperthermia experiments using the noninvasive magnetic resonance imaging (MRI) thermometry. Methods A 3D acoustical prostate model was created using photographic data from the Visible Human Project®. The k-space computational method was used on this coarse grid and inhomogeneous tissue model to simulate the steady state pressure wavefield of the designed phased array using the linear acoustic wave equation. To ensure the uniformity and spread of the pressure in the length of the array, and the focusing capability in the width of the array, the equally-sized elements of the 4 × 20 elements phased array were 1 × 14 mm. A probe was constructed according to the design in simulation using lead zerconate titanate (PZT-8) ceramic and a Delrin® plastic housing. Noninvasive MRI thermometry and a switching feedback controller were used to accomplish ex vivo and in vivo hyperthermia evaluations of the probe. Results Both exposimetry and k-space simulation results demonstrated acceptable agreement within 9%. With a desired temperature plateau of 43.0°C, ex vivo and in vivo controlled hyperthermia experiments showed that the MRI temperature at the steady state was 42.9 ± 0.38°C and 43.1 ± 0.80°C, respectively, for 20 minutes of heating. Conclusion Unlike conventional computational methods, the k-space method provides a powerful tool to predict pressure wavefield in large scale, 3D, inhomogeneous and coarse grid tissue models. Noninvasive MRI thermometry supports the efficacy of this probe and the feedback controller in an in vivo hyperthermia treatment of canine prostate. PMID:17064421

MR thermometry characterization of a hyperthermia ultrasound array designed using the k-space computational method.

PubMed

Al-Bataineh, Osama M; Collins, Christopher M; Park, Eun-Joo; Lee, Hotaik; Smith, Nadine Barrie

2006-10-25

Ultrasound induced hyperthermia is a useful adjuvant to radiation therapy in the treatment of prostate cancer. A uniform thermal dose (43 degrees C for 30 minutes) is required within the targeted cancerous volume for effective therapy. This requires specific ultrasound phased array design and appropriate thermometry method. Inhomogeneous, acoustical, three-dimensional (3D) prostate models and economical computational methods provide necessary tools to predict the appropriate shape of hyperthermia phased arrays for better focusing. This research utilizes the k-space computational method and a 3D human prostate model to design an intracavitary ultrasound probe for hyperthermia treatment of prostate cancer. Evaluation of the probe includes ex vivo and in vivo controlled hyperthermia experiments using the noninvasive magnetic resonance imaging (MRI) thermometry. A 3D acoustical prostate model was created using photographic data from the Visible Human Project. The k-space computational method was used on this coarse grid and inhomogeneous tissue model to simulate the steady state pressure wavefield of the designed phased array using the linear acoustic wave equation. To ensure the uniformity and spread of the pressure in the length of the array, and the focusing capability in the width of the array, the equally-sized elements of the 4 x 20 elements phased array were 1 x 14 mm. A probe was constructed according to the design in simulation using lead zerconate titanate (PZT-8) ceramic and a Delrin plastic housing. Noninvasive MRI thermometry and a switching feedback controller were used to accomplish ex vivo and in vivo hyperthermia evaluations of the probe. Both exposimetry and k-space simulation results demonstrated acceptable agreement within 9%. With a desired temperature plateau of 43.0 degrees C, ex vivo and in vivo controlled hyperthermia experiments showed that the MRI temperature at the steady state was 42.9 +/- 0.38 degrees C and 43.1 +/- 0.80 degrees C, respectively, for 20 minutes of heating. Unlike conventional computational methods, the k-space method provides a powerful tool to predict pressure wavefield in large scale, 3D, inhomogeneous and coarse grid tissue models. Noninvasive MRI thermometry supports the efficacy of this probe and the feedback controller in an in vivo hyperthermia treatment of canine prostate.

Functional Validation of H2 Relaxin, and its Downstream Effectors, as Mediators, Therapeutic Targets and Potential Biomarkers of Prostate Cancer Progression

DTIC Science & Technology

2011-06-01

contribute to CR growth. Inhibition of PKA attenuated RLN2-mediated AR activity, inhibited proliferation and caused a small but significant increase in...detection of p53 abnormalities and increases their predictive value. BJU Int 94: 996–1002. Silvertown JD, Geddes BJ, Summerlee AJ. (2003). Adenovirus ...in facilitating H2 relaxin-mediated CR growth of CaP cells. Inhibition of PKA attenuated RLN2-mediated AR activity, inhibited proliferation and

Towards clinical application of RayStretch for heterogeneity corrections in LDR permanent 125I prostate brachytherapy.

PubMed

Hueso-González, Fernando; Ballester, Facundo; Perez-Calatayud, Jose; Siebert, Frank-André; Vijande, Javier

RayStretch is a simple algorithm proposed for heterogeneity corrections in low-dose-rate brachytherapy. It is built on top of TG-43 consensus data, and it has been validated with Monte Carlo (MC) simulations. In this study, we take a real clinical prostate implant with 71 125 I seeds as reference and we apply RayStretch to analyze its performance in worst-case scenarios. To do so, we design two cases where large calcifications are located in the prostate lobules. RayStretch resilience under various calcification density values is also explored. Comparisons against MC calculations are performed. Dose-volume histogram-related parameters like prostate D 90 , rectum D 2cc , or urethra D 10 obtained with RayStretch agree within a few percent with the detailed MC results for all cases considered. The robustness and compatibility of RayStretch with commercial treatment planning systems indicate its applicability in clinical practice for dosimetric corrections in prostate calcifications. Its use during intraoperative ultrasound planning is foreseen. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Accuracy of localization of prostate lesions using manual palpation and ultrasound elastography

NASA Astrophysics Data System (ADS)

Kut, Carmen; Schneider, Caitlin; Carter-Monroe, Naima; Su, Li-Ming; Boctor, Emad; Taylor, Russell

2009-02-01

Purpose: To compare the accuracy of detecting tumor location and size in the prostate using both manual palpation and ultrasound elastography (UE). Methods: Tumors in the prostate were simulated using both synthetic and ex vivo tissue phantoms. 25 participants were asked to provide the presence, size and depth of these simulated lesions using manual palpation and UE. Ultrasound images were captured using a laparoscopic ultrasound probe, fitted with a Gore-Tetrad transducer with frequency of 7.5 MHz and a RF capture depth of 4-5 cm. A MATLAB GUI application was employed to process the RF data for ex vivo phantoms, and to generate UE images using a cross-correlation algorithm. Ultrasonix software was used to provide real time elastography during laparoscopic palpation of the synthetic phantoms. Statistical analyses were performed based on a two-tailed, student t-test with α = 0.05. Results: UE displays both a higher accuracy and specificity in tumor detection (sensitivity = 84%, specificity = 74%). Tumor diameters and depths are better estimated using ultrasound elastography when compared with manual palpation. Conclusions: Our results indicate that UE has strong potential in assisting surgeons to intra-operatively evaluate the tumor depth and size. We have also demonstrated that ultrasound elastography can be implemented in a laparoscopic environment, in which manual palpation would not be feasible. With further work, this application can provide accurate and clinically relevant information for surgeons during prostate resection.

An Adaptive MR-CT Registration Method for MRI-guided Prostate Cancer Radiotherapy

PubMed Central

Zhong, Hualiang; Wen, Ning; Gordon, James; Elshaikh, Mohamed A; Movsas, Benjamin; Chetty, Indrin J.

2015-01-01

Magnetic Resonance images (MRI) have superior soft tissue contrast compared with CT images. Therefore, MRI might be a better imaging modality to differentiate the prostate from surrounding normal organs. Methods to accurately register MRI to simulation CT images are essential, as we transition the use of MRI into the routine clinic setting. In this study, we present a finite element method (FEM) to improve the performance of a commercially available, B-spline-based registration algorithm in the prostate region. Specifically, prostate contours were delineated independently on ten MRI and CT images using the Eclipse treatment planning system. Each pair of MRI and CT images was registered with the B-spline-based algorithm implemented in the VelocityAI system. A bounding box that contains the prostate volume in the CT image was selected and partitioned into a tetrahedral mesh. An adaptive finite element method was then developed to adjust the displacement vector fields (DVFs) of the B-spline-based registrations within the box. The B-spline and FEM-based registrations were evaluated based on the variations of prostate volume and tumor centroid, the unbalanced energy of the generated DVFs, and the clarity of the reconstructed anatomical structures. The results showed that the volumes of the prostate contours warped with the B-spline-based DVFs changed 10.2% on average, relative to the volumes of the prostate contours on the original MR images. This discrepancy was reduced to 1.5% for the FEM-based DVFs. The average unbalanced energy was 2.65 and 0.38 mJ/cm3, and the prostate centroid deviation was 0.37 and 0.28 cm, for the B-spline and FEM-based registrations, respectively. Different from the B-spline-warped MR images, the FEM-warped MR images have clear boundaries between prostates and bladders, and their internal prostatic structures are consistent with those of the original MR images. In summary, the developed adaptive FEM method preserves the prostate volume during the transformation between the MR and CT images and improves the accuracy of the B-spline registrations in the prostate region. The approach will be valuable for development of high-quality MRI-guided radiation therapy. PMID:25775937

An adaptive MR-CT registration method for MRI-guided prostate cancer radiotherapy

NASA Astrophysics Data System (ADS)

Zhong, Hualiang; Wen, Ning; Gordon, James J.; Elshaikh, Mohamed A.; Movsas, Benjamin; Chetty, Indrin J.

2015-04-01

Magnetic Resonance images (MRI) have superior soft tissue contrast compared with CT images. Therefore, MRI might be a better imaging modality to differentiate the prostate from surrounding normal organs. Methods to accurately register MRI to simulation CT images are essential, as we transition the use of MRI into the routine clinic setting. In this study, we present a finite element method (FEM) to improve the performance of a commercially available, B-spline-based registration algorithm in the prostate region. Specifically, prostate contours were delineated independently on ten MRI and CT images using the Eclipse treatment planning system. Each pair of MRI and CT images was registered with the B-spline-based algorithm implemented in the VelocityAI system. A bounding box that contains the prostate volume in the CT image was selected and partitioned into a tetrahedral mesh. An adaptive finite element method was then developed to adjust the displacement vector fields (DVFs) of the B-spline-based registrations within the box. The B-spline and FEM-based registrations were evaluated based on the variations of prostate volume and tumor centroid, the unbalanced energy of the generated DVFs, and the clarity of the reconstructed anatomical structures. The results showed that the volumes of the prostate contours warped with the B-spline-based DVFs changed 10.2% on average, relative to the volumes of the prostate contours on the original MR images. This discrepancy was reduced to 1.5% for the FEM-based DVFs. The average unbalanced energy was 2.65 and 0.38 mJ cm-3, and the prostate centroid deviation was 0.37 and 0.28 cm, for the B-spline and FEM-based registrations, respectively. Different from the B-spline-warped MR images, the FEM-warped MR images have clear boundaries between prostates and bladders, and their internal prostatic structures are consistent with those of the original MR images. In summary, the developed adaptive FEM method preserves the prostate volume during the transformation between the MR and CT images and improves the accuracy of the B-spline registrations in the prostate region. The approach will be valuable for the development of high-quality MRI-guided radiation therapy.

A phase and frequency alignment protocol for 1H MRSI data of the prostate.

PubMed

Wright, Alan J; Buydens, Lutgarde M C; Heerschap, Arend

2012-05-01

(1)H MRSI of the prostate reveals relative metabolite levels that vary according to the presence or absence of tumour, providing a sensitive method for the identification of patients with cancer. Current interpretations of prostate data rely on quantification algorithms that fit model metabolite resonances to individual voxel spectra and calculate relative levels of metabolites, such as choline, creatine, citrate and polyamines. Statistical pattern recognition techniques can potentially improve the detection of prostate cancer, but these analyses are hampered by artefacts and sources of noise in the data, such as variations in phase and frequency of resonances. Phase and frequency variations may arise as a result of spatial field gradients or local physiological conditions affecting the frequency of resonances, in particular those of citrate. Thus, there are unique challenges in developing a peak alignment algorithm for these data. We have developed a frequency and phase correction algorithm for automatic alignment of the resonances in prostate MRSI spectra. We demonstrate, with a simulated dataset, that alignment can be achieved to a phase standard deviation of 0.095  rad and a frequency standard deviation of 0.68  Hz for the citrate resonances. Three parameters were used to assess the improvement in peak alignment in the MRSI data of five patients: the percentage of variance in all MRSI spectra explained by their first principal component; the signal-to-noise ratio of a spectrum formed by taking the median value of the entire set at each spectral point; and the mean cross-correlation between all pairs of spectra. These parameters showed a greater similarity between spectra in all five datasets and the simulated data, demonstrating improved alignment for phase and frequency in these spectra. This peak alignment program is expected to improve pattern recognition significantly, enabling accurate detection and localisation of prostate cancer with MRSI. Copyright © 2011 John Wiley & Sons, Ltd.

Prostate-Specific Antigen-Based Screening for Prostate Cancer: Evidence Report and Systematic Review for the US Preventive Services Task Force.

PubMed

Fenton, Joshua J; Weyrich, Meghan S; Durbin, Shauna; Liu, Yu; Bang, Heejung; Melnikow, Joy

2018-05-08

Prostate cancer is the second leading cause of cancer death among US men. To systematically review evidence on prostate-specific antigen (PSA)-based prostate cancer screening, treatments for localized prostate cancer, and prebiopsy risk calculators to inform the US Preventive Services Task Force. Searches of PubMed, EMBASE, Web of Science, and Cochrane Registries and Databases from July 1, 2011, through July 15, 2017, with a surveillance search on February 1, 2018. English-language reports of randomized clinical trials (RCTs) of screening; cohort studies reporting harms; RCTs and cohort studies of active localized cancer treatments vs conservative approaches (eg, active surveillance, watchful waiting); external validations of prebiopsy risk calculators to identify aggressive cancers. One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. Prostate cancer and all-cause mortality; false-positive screening results, biopsy complications, overdiagnosis; adverse effects of active treatments. Random-effects meta-analyses were conducted for treatment harms. Sixty-three studies in 104 publications were included (N = 1 904 950). Randomization to PSA screening was not associated with reduced risk of prostate cancer mortality in either a US trial with substantial control group contamination (n = 76 683) or a UK trial with low adherence to a single PSA screen (n = 408 825) but was associated with significantly reduced prostate cancer mortality in a European trial (n = 162 243; relative risk [RR], 0.79 [95% CI, 0.69-0.91]; absolute risk reduction, 1.1 deaths per 10 000 person-years [95% CI, 0.5-1.8]). Of 61 604 men screened in the European trial, 17.8% received false-positive results. In 3 cohorts (n = 15 136), complications requiring hospitalization occurred in 0.5% to 1.6% of men undergoing biopsy after abnormal screening findings. Overdiagnosis was estimated to occur in 20.7% to 50.4% of screen-detected cancers. In an RCT of men with screen-detected prostate cancer (n = 1643), neither radical prostatectomy (hazard ratio [HR], 0.63 [95% CI, 0.21-1.93]) nor radiation therapy (HR, 0.51 [95% CI, 0.15-1.69]) were associated with significantly reduced prostate cancer mortality vs active monitoring, although each was associated with significantly lower risk of metastatic disease. Relative to conservative management, radical prostatectomy was associated with increased risk of urinary incontinence (pooled RR, 2.27 [95% CI, 1.82-2.84]; 3 trials; n = 1796) and erectile dysfunction (pooled RR, 1.82 [95% CI, 1.62-2.04]; 2 trials; n = 883). Relative to conservative management (8 cohort studies; n = 3066), radiation therapy was associated with increased risk of erectile dysfunction (pooled RR, 1.31 [95% CI, 1.20-1.42]). PSA screening may reduce prostate cancer mortality risk but is associated with false-positive results, biopsy complications, and overdiagnosis. Compared with conservative approaches, active treatments for screen-detected prostate cancer have unclear effects on long-term survival but are associated with sexual and urinary difficulties.

Multivariate analysis of factors predicting prostate dose in intensity-modulated radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomita, Tsuneyuki; Nakamura, Mitsuhiro, E-mail: m_nkmr@kuhp.kyoto-u.ac.jp; Hirose, Yoshinori

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 weremore » 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.« less

Relationship Between Prebiopsy Multiparametric Magnetic Resonance Imaging (MRI), Biopsy Indication, and MRI-ultrasound Fusion-targeted Prostate Biopsy Outcomes.

PubMed

Meng, Xiaosong; Rosenkrantz, Andrew B; Mendhiratta, Neil; Fenstermaker, Michael; Huang, Richard; Wysock, James S; Bjurlin, Marc A; Marshall, Susan; Deng, Fang-Ming; Zhou, Ming; Melamed, Jonathan; Huang, William C; Lepor, Herbert; Taneja, Samir S

2016-03-01

Increasing evidence supports the use of magnetic resonance imaging (MRI)-ultrasound fusion-targeted prostate biopsy (MRF-TB) to improve the detection of clinically significant prostate cancer (PCa) while limiting detection of indolent disease compared to systematic 12-core biopsy (SB). To compare MRF-TB and SB results and investigate the relationship between biopsy outcomes and prebiopsy MRI. Retrospective analysis of a prospectively acquired cohort of men presenting for prostate biopsy over a 26-mo period. A total of 601 of 803 consecutively eligible men were included. All men were offered prebiopsy MRI and assigned a maximum MRI suspicion score (mSS). Men with an MRI abnormality underwent combined MRF-TB and SB. Detection rates for all PCa and high-grade PCa (Gleason score [GS] ≥7) were compared using the McNemar test. MRF-TB detected fewer GS 6 PCas (75 vs 121; p<0.001) and more GS ≥7 PCas (158 vs 117; p<0.001) than SB. Higher mSS was associated with higher detection of GS ≥7 PCa (p<0.001) but was not correlated with detection of GS 6 PCa. Prediction of GS ≥7 disease by mSS varied according to biopsy history. Compared to SB, MRF-TB identified more GS ≥7 PCas in men with no prior biopsy (88 vs 72; p=0.012), in men with a prior negative biopsy (28 vs 16; p=0.010), and in men with a prior cancer diagnosis (42 vs 29; p=0.043). MRF-TB detected fewer GS 6 PCas in men with no prior biopsy (32 vs 60; p<0.001) and men with prior cancer (30 vs 46; p=0.034). Limitations include the retrospective design and the potential for selection bias given a referral population. MRF-TB detects more high-grade PCas than SB while limiting detection of GS 6 PCa in men presenting for prostate biopsy. These findings suggest that prebiopsy multiparametric MRI and MRF-TB should be considered for all men undergoing prostate biopsy. In addition, mSS in conjunction with biopsy indications may ultimately help in identifying men at low risk of high-grade cancer for whom prostate biopsy may not be warranted. We examined how magnetic resonance imaging (MRI)-targeted prostate biopsy compares to traditional systematic biopsy in detecting prostate cancer among men with suspicion of prostate cancer. We found that MRI-targeted biopsy detected more high-grade cancers than systematic biopsy, and that MRI performed before biopsy can predict the risk of high-grade cancer. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Antagonizing effects of membrane-acting androgens on the eicosanoid receptor OXER1 in prostate cancer

PubMed Central

Kalyvianaki, Konstantina; Gebhart, Veronika; Peroulis, Nikolaos; Panagiotopoulou, Christina; Kiagiadaki, Fotini; Pediaditakis, Iosif; Aivaliotis, Michalis; Moustou, Eleni; Tzardi, Maria; Notas, George; Castanas, Elias; Kampa, Marilena

2017-01-01

Accumulating evidence during the last decades revealed that androgen can exert membrane initiated actions that involve signaling via specific kinases and the modulation of significant cellular processes, important for prostate cancer cell growth and metastasis. Results of the present work clearly show that androgens can specifically act at the membrane level via the GPCR oxoeicosanoid receptor 1 (OXER1) in prostate cancer cells. In fact, OXER1 expression parallels that of membrane androgen binding in prostate cancer cell lines and tumor specimens, while in silico docking simulation of OXER1 showed that testosterone could bind to OXER1 within the same grove as 5-OxoETE, the natural ligand of OXER1. Interestingly, testosterone antagonizes the effects of 5-oxoETE on specific signaling pathways and rapid effects such as actin cytoskeleton reorganization that ultimately can modulate cell migration and metastasis. These findings verify that membrane-acting androgens exert specific effects through an antagonistic interaction with OXER1. Additionally, this interaction between androgen and OXER1, which is an arachidonic acid metabolite receptor expressed in prostate cancer, provides a novel link between steroid and lipid actions and renders OXER1 as new player in the disease. These findings should be taken into account in the design of novel therapeutic approaches in prostate cancer. PMID:28290516

Low grade urothelial carcinoma mimicking basal cell hyperplasia and transitional metaplasia in needle prostate biopsy.

PubMed

Arista-Nasr, Julian; Martinez-Benitez, Braulio; Bornstein-Quevedo, Leticia; Aguilar-Ayala, Elizmara; Aleman-Sanchez, Claudia Natalia; Ortiz-Bautista, Raul

2016-01-01

The vast majority of urothelial carcinomas infiltrating the bladder are consistente with high-grade tumors that can be easily recognized as malignant in needle prostatic biopsies. In contrast, the histological changes of low-grade urothelial carcinomas in this kind of biopsy have not been studied. We describe the clinicopathologic features of two patients with low-grade bladder carcinomas infiltrating the prostate. They reported dysuria and hematuria. Both had a slight elevation of the prostate specific antigen and induration of the prostatic lobes. Needle biopsies were performed. At endoscopy bladder tumors were found in both cases. Both biopsies showed nests of basophilic cells and cells with perinuclear clearing and slight atypia infiltrating acini and small prostatic ducts. The stroma exhibited extensive desmoplasia and chronic inflammation. The original diagnosis was basal cell hyperplasia and transitional metaplasia. The bladder tumors also showed low-grade urothelial carcinoma. In one case, the neoplasm infiltrated the lamina propria, and in another, the muscle layer. In both, a transurethral resection was performed for obstructive urinary symptoms. The neoplasms were positive for high molecular weight keratin (34BetaE12) and thrombomodulin. No metastases were found in either of the patients, and one of them has survived for five years. The diagnosis of low-grade urothelial carcinoma in prostate needle biopsies is difficult and may simulate benign prostate lesions including basal cell hyperplasia and urothelial metaplasia. It is crucial to recognize low-grade urothelial carcinoma in needle biopsies because only an early diagnosis and aggressive treatment can improve the prognosis for these patients.

Texas Native Plants Yield Compounds with Cytotoxic Activities against Prostate Cancer Cells.

PubMed

Shaffer, Corena V; Cai, Shengxin; Peng, Jiangnan; Robles, Andrew J; Hartley, Rachel M; Powell, Douglas R; Du, Lin; Cichewicz, Robert H; Mooberry, Susan L

2016-03-25

There remains a critical need for more effective therapies for the treatment of late-stage and metastatic prostate cancers. Three Texas native plants yielded three new and three known compounds with antiproliferative and cytotoxic activities against prostate cancer cells with IC50 values in the range of 1.7-35.0 μM. A new sesquiterpene named espadalide (1), isolated from Gochnatia hypoleuca, had low micromolar potency and was highly effective in clonogenic assays. Two known bioactive germacranolides (2 and 3) were additionally isolated from G. hypoleuca. Dalea frutescens yielded two new isoprenylated chalcones, named sanjuanolide (4) and sanjoseolide (5), and the known sesquiterpenediol verbesindiol (6) was isolated from Verbesina virginica. Mechanistic studies showed that 1-4 caused G2/M accumulation and the formation of abnormal mitotic spindles. Tubulin polymerization assays revealed that 4 increased the initial rate of tubulin polymerization, but did not change total tubulin polymer levels, and 1-3 had no effects on tubulin polymerization. Despite its cytotoxic activity, compound 6 did not initiate changes in cell cycle distribution and has a mechanism of action different from the other compounds. This study demonstrates that new compounds with significant biological activities germane to unmet oncological needs can be isolated from Texas native plants.

Silodosin: treatment of the signs and symptoms of benign prostatic hyperplasia.

PubMed

Curran, Monique P

2011-05-07

Silodosin is an α-adrenoceptor antagonist with high selectivity for α(1A)- relative to α(1B)- adrenoceptors. In men aged >50 years with benign prostatic hyperplasia (BPH), silodosin 8 mg once daily, compared with placebo, was associated with a significantly more rapid and effective improvement in the total International Prostate Symptom Score (IPSS) and the storage and voiding IPSS subscores in three 12-week, phase III trials conducted in Europe and the US. In the European trial, silodosin was at least as effective as tamsulosin 0.4 mg once daily in improving the total IPSS. Silodosin was significantly more effective than placebo (all three phase III trials) and tamsulosin (European phase III trial) in simultaneously improving nocturia, frequency and incomplete emptying, according to a post hoc analysis. Long-term, open-label extension trials demonstrated that silodosin provided sustained relief of the signs and symptoms of BPH for up to 1 year. Silodosin was generally well tolerated, and was associated with minimal cardiovascular adverse effects. Abnormal ejaculation, a class effect of α(1A)-adrenoceptor antagonists, was the most common silodosin-associated adverse reaction, but resulted in treatment withdrawal of only a limited number of patients. © 2011 Adis Data Information BV. All rights reserved.

Dietary factors and epigenetic regulation for prostate cancer prevention.

PubMed

Ho, Emily; Beaver, Laura M; Williams, David E; Dashwood, Roderick H

2011-11-01

The role of epigenetic alterations in various human chronic diseases has gained increasing attention and has resulted in a paradigm shift in our understanding of disease susceptibility. In the field of cancer research, e.g., genetic abnormalities/mutations historically were viewed as primary underlying causes; however, epigenetic mechanisms that alter gene expression without affecting DNA sequence are now recognized as being of equal or greater importance for oncogenesis. Methylation of DNA, modification of histones, and interfering microRNA (miRNA) collectively represent a cadre of epigenetic elements dysregulated in cancer. Targeting the epigenome with compounds that modulate DNA methylation, histone marks, and miRNA profiles represents an evolving strategy for cancer chemoprevention, and these approaches are starting to show promise in human clinical trials. Essential micronutrients such as folate, vitamin B-12, selenium, and zinc as well as the dietary phytochemicals sulforaphane, tea polyphenols, curcumin, and allyl sulfur compounds are among a growing list of agents that affect epigenetic events as novel mechanisms of chemoprevention. To illustrate these concepts, the current review highlights the interactions among nutrients, epigenetics, and prostate cancer susceptibility. In particular, we focus on epigenetic dysregulation and the impact of specific nutrients and food components on DNA methylation and histone modifications that can alter gene expression and influence prostate cancer progression.

SU-F-J-156: The Feasibility of MR-Only IMRT Planning for Prostate Anatomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vaitheeswaran, R; Sivaramakrishnan, KR; Kumar, Prashant

Purpose: For prostate anatomy, previous investigations have shown that simulated CT (sCT) generated from MR images can be used for accurate dose computation. In this study, we demonstrate the feasibility of MR-only IMRT planning for prostate case. Methods: Regular CT (rCT) and MR images of the same patient were acquired for prostate anatomy. Regions-of-interest (ROIs) i.e. target and risk structures are delineated on the rCT. A simulated CT (sCT) is generated from the MR image using the method described by Schadewaldt N et al. Their work establishes the clinical acceptability of dose calculation results on the sCT when compared tomore » rCT. rCT and sCT are rigidly registered to ensure proper alignment between the two images. rCT and sCT are overlaid on each other and slice-wise visual inspection confirms excellent agreement between the two images. ROIs on the rCT are copied over to sCT. Philips AutoPlanning solution is used for generating treatment plans. The same treatment technique protocol (plan parameters and clinical goals) is used to generate AutoPlan-rCT and AutoPlan-sCT respectively for rCT and and sCT. DVH comparison on ROIs and slice-wise evaluation of dose is performed between AutoPlan-rCT and AutoPlan-sCT. Delivery parameters i.e. beam and corresponding segments from the AutoPlan-sCT are copied over to rCT and dose is computed to get AutoPlan-sCT-on-rCT. Results: Plan evaluation is done based on Dose Volume Histogram (DVH) of ROIs and manual slice-wise inspection of dose distribution. Both AutoPlan-rCT and AutoPlan-sCT provide a clinically acceptable plan. Also, AutoPlan-sCT-on-rCT shows excellent agreement with AutoPlan-sCT. Conclusion: The study demonstrates that it is feasible to do IMRT planning on the simulated CT image obtained from MR image for prostate anatomy. The research is supported by Philips India Ltd.« less

Face validity, construct validity and training benefits of a virtual reality TURP simulator.

PubMed

Bright, Elizabeth; Vine, Samuel; Wilson, Mark R; Masters, Rich S W; McGrath, John S

2012-01-01

To assess face validity, construct validity and the training benefits of a virtual reality TURP simulator. 11 novices (no TURP experience) and 7 experts (>200 TURP's) completed a virtual reality median lobe prostate resection task on the TURPsim™ (Simbionix USA Corp., Cleveland, OH). Performance indicators (percentage of prostate resected (PR), percentage of capsular resection (CR) and time diathermy loop active without tissue contact (TAWC) were recorded via the TURPsim™ and compared between novices and experts to assess construct validity. Verbal comments provided by experts following task completion were used to assess face validity. Repeated attempts of the task by the novices were analysed to assess the training benefits of the TURPsim™. Experts resected a significantly greater percentage of prostate per minute (p < 0.01) and had significantly less active diathermy time without tissue contact (p < 0.01) than novices. After practice, novices were able to perform the simulation more effectively, with significant improvement in all measured parameters. Improvement in performance was noted in novices following repetitive training, as evidenced by improved TAWC scores that were not significantly different from the expert group (p = 0.18). This study has established face and construct validity for the TURPsim™. The potential benefit in using this tool to train novices has also been demonstrated. Copyright © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Effects of organ motion on proton prostate treatments, as determined from analysis of daily CT imaging for patient positioning.

PubMed

Maeda, Yoshikazu; Sato, Yoshitaka; Shibata, Satoshi; Bou, Sayuri; Yamamoto, Kazutaka; Tamamura, Hiroyasu; Fuwa, Nobukazu; Takamatsu, Shigeyuki; Sasaki, Makoto; Tameshige, Yuji; Kume, Kyo; Minami, Hiroki; Saga, Yusuke; Saito, Makoto

2018-05-01

We quantified interfractional movements of the prostate, seminal vesicles (SVs), and rectum during computed tomography (CT) image-guided proton therapy for prostate cancer and studied the range variation in opposed lateral proton beams. We analyzed 375 sets of daily CT images acquired throughout the proton therapy treatment of ten patients. We analyzed daily movements of the prostate, SVs, and rectum by simulating three image-matching strategies: bone matching, prostate center (PC) matching, and prostate-rectum boundary (PRB) matching. In the PC matching, translational movements of the prostate center were corrected after bone matching. In the PRB matching, we performed PC matching and correction along the anterior-posterior direction to match the boundary between the prostate and the rectum's anterior region. In each strategy, we evaluated systematic errors (Σ) and random errors (σ) by measuring the daily movements of certain points on each anatomic structure. The average positional deviations in millimeter of each point were determined by the Van Herk formula of 2.5Σ + 0.7σ. Using these positional deviations, we created planning target volumes of the prostate and SVs and analyzed the daily variation in the water equivalent length (WEL) from the skin surface to the target along the lateral beam directions using the density converted from the daily CT number. Based on this analysis, we designed prostate cancer treatment planning and evaluated the dose volume histograms (DVHs) for these strategies. The SVs' daily movements showed large variations over the superior-inferior direction, as did the rectum's anterior region. The average positional deviations of the prostate in the anterior, posterior, superior, inferior, and lateral sides (mm) in bone matching, PC matching, and PRB matching were (8.9, 9.8, 7.5, 3.6, 1.6), (5.6, 6.1, 3.5, 4.5, 1.9), and (8.6, 3.2, 3.5, 4.5, 1.9) (mm), respectively. Moreover, the ones of the SV tip were similarly (22.5, 15.5, 11.0, 7.6, 6.0), (11.8, 8.4, 7.8, 5.2, 6.3), and (9.9, 7.5, 7.8, 5.2, 6.3). PRB matching showed the smallest positional deviations at all portions except for the anterior portion of the prostate and was able to markedly reduce the positional deviations at the posterior portion. The averaged WEL variations at the distal and proximal sides of planning target volumes were estimated 7-9 mm and 4-6 mm, respectively, and showed the increasing of a few millimeters in PC and PRB matching compared to bone matching. In the treatment planning simulation, the DVH values of the rectum in PRB matching were reduced compared to those obtained with other matching strategies. The positional deviations for the prostate on the posterior side and the SVs were smaller by PRB matching than the other strategies and effectively reduced the rectal dose. 3D dose calculations indicate that PRB matching with CT image guidance may do a better job relative to other positioning methods to effectively reduce the rectal complications. The WEL variation was quite large, and the appropriate margin (approx. 10 mm) must be adapted to the proton range in an initial planning to maintain the coverage of target volumes throughout entire treatment. © 2018 American Association of Physicists in Medicine.

Laser Treatment of Benign Prostatic Hyperplasia: Dosimetric and Thermodynamic Considerations

NASA Astrophysics Data System (ADS)

Anvari, Bahman

1993-01-01

Benign prostatic hyperplasia (BPH) is the most commonly occurring neoplastic disease in the aging human male. Currently, surgical treatment of BPH is the primary therapeutic method. However, due to surgical complications, less invasive methods of treatment are desirable. In recent years, thermal coagulation of the hyperplastic prostate by a laser has received a considerable amount of attention. Nevertheless, the optimum laser irradiation parameters that lead to a successful and safe treatment of BPH have not been determined. This dissertation studies the physics of laser coagulation of prostate from both basic science and practical perspectives. Optical properties of prostatic tissue are determined over a spectrum of wavelengths. Knowledge of these properties allows for selection of appropriate laser wavelengths and provides a basis for performing dose equivalency studies among various types of lasers. Furthermore, knowledge of optical properties are needed for development of computer simulation models that predict the extent of thermal injury during laser irradiation of prostate. A computer model of transurethral heating of prostate that can be used to guide the clinical studies in determining an optimum dosimetry is then presented. Studies of the effects of non-laser heating devices, optical properties, blood perfusion, surface irrigation, and beam geometry are performed to examine the extent of heat propagation within the prostate. An in vitro model for transurethral laser irradiation of prostate is also presented to examine the effects of an 810 nm diode laser, thermal boundary conditions, and energy deposition rate during Nd:YAG laser irradiation. Results of these studies suggest that in the presence of laminar irrigation, the convective boundary condition is dominated by thermal diffusion as opposed to the bulk motion of the irrigation fluid. Distinct phases of thermal events are also identified during the laser irradiation. The in vivo studies of transurethral laser irradiation of prostate in canine models are also performed to search for an optimum dosimetry that will result in a maximum zone of coagulation necrosis.

Desquamation takes center stage at the origin of proliferative inflammatory atrophy, epithelial-mesenchymal transition, and stromal growth in benign prostate hyperplasia.

PubMed

Ferrucci, Danilo; Biancardi, Manoel F; Nishan, Umar; Rosa-Ribeiro, Rafaela; Carvalho, Hernandes F

2017-11-01

In this commentary, we propose a relationship between desquamation, initially described as the collective detachment and deletion of epithelial cell in the prostate gland after castration, and proliferative inflammatory atrophy (PIA) and stromal growth in benign prostate hyperplasia (BPH). First, in response to diverse stimuli, including inflammatory mediators, epithelial cells desquamate and leave a large surface of the luminal side of the basement membrane (BM) exposed. Basal cells are activated into intermediate-type cells, which change morphology to cover and remodel the exposed BM (simple atrophy) to a new physiological demand (such as in the hypoandrogen environment, simulated by surgical and/or chemical castration) and/or to support re-epithelialization (under normal androgen levels). In the presence of inflammation (that might be the cause of desquamation), the intermediate-type cells proliferate and characterize PIA. Second, in other circumstances, desquamation is an early step of epithelial-to-mesenchymal transition (EMT), which contributes to stromal growth, as suggested by some experimental models of BPH. The proposed associations correlate unexplored cell behaviors and reveal the remarkable plasticity of the prostate epithelium that might be at the origin of prostate diseases. © 2017 International Federation for Cell Biology.

Simulation of realistic abnormal SPECT brain perfusion images: application in semi-quantitative analysis

NASA Astrophysics Data System (ADS)

Ward, T.; Fleming, J. S.; Hoffmann, S. M. A.; Kemp, P. M.

2005-11-01

Simulation is useful in the validation of functional image analysis methods, particularly when considering the number of analysis techniques currently available lacking thorough validation. Problems exist with current simulation methods due to long run times or unrealistic results making it problematic to generate complete datasets. A method is presented for simulating known abnormalities within normal brain SPECT images using a measured point spread function (PSF), and incorporating a stereotactic atlas of the brain for anatomical positioning. This allows for the simulation of realistic images through the use of prior information regarding disease progression. SPECT images of cerebral perfusion have been generated consisting of a control database and a group of simulated abnormal subjects that are to be used in a UK audit of analysis methods. The abnormality is defined in the stereotactic space, then transformed to the individual subject space, convolved with a measured PSF and removed from the normal subject image. The dataset was analysed using SPM99 (Wellcome Department of Imaging Neuroscience, University College, London) and the MarsBaR volume of interest (VOI) analysis toolbox. The results were evaluated by comparison with the known ground truth. The analysis showed improvement when using a smoothing kernel equal to system resolution over the slightly larger kernel used routinely. Significant correlation was found between effective volume of a simulated abnormality and the detected size using SPM99. Improvements in VOI analysis sensitivity were found when using the region median over the region mean. The method and dataset provide an efficient methodology for use in the comparison and cross validation of semi-quantitative analysis methods in brain SPECT, and allow the optimization of analysis parameters.

Effect of Time-Dependent Pinning Pressure on Abnormal Grain Growth: Phase Field Simulation

NASA Astrophysics Data System (ADS)

Kim, Jeong Min; Min, Guensik; Shim, Jae-Hyeok; Lee, Kyung Jong

2018-05-01

The effect of the time-dependent pinning pressure of precipitates on abnormal grain growth has been investigated by multiphase field simulation with a simple precipitation model. The application of constant pinning pressure is problematic because it always induces abnormal grain growth or no grain growth, which is not reasonable considering the real situation. To produce time-dependent pinning pressure, both precipitation kinetics and precipitate coarsening kinetics have been considered with two rates: slow and fast. The results show that abnormal grain growth is suppressed at the slow precipitation rate. At the slow precipitation rate, the overall grain growth caused by the low pinning pressure in the early stage indeed plays a role in preventing abnormal grain growth by reducing the mobility advantage of abnormal grains. In addition, the fast precipitate coarsening rate tends to more quickly transform abnormal grain growth into normal grain growth by inducing the active growth of grains adjacent to the abnormal grains in the early stage. Therefore, the present study demonstrates that the time dependence of the pinning pressure of precipitates is a critical factor that determines the grain growth mode.

Effect of Time-Dependent Pinning Pressure on Abnormal Grain Growth: Phase Field Simulation

NASA Astrophysics Data System (ADS)

Kim, Jeong Min; Min, Guensik; Shim, Jae-Hyeok; Lee, Kyung Jong

2018-03-01

The effect of the time-dependent pinning pressure of precipitates on abnormal grain growth has been investigated by multiphase field simulation with a simple precipitation model. The application of constant pinning pressure is problematic because it always induces abnormal grain growth or no grain growth, which is not reasonable considering the real situation. To produce time-dependent pinning pressure, both precipitation kinetics and precipitate coarsening kinetics have been considered with two rates: slow and fast. The results show that abnormal grain growth is suppressed at the slow precipitation rate. At the slow precipitation rate, the overall grain growth caused by the low pinning pressure in the early stage indeed plays a role in preventing abnormal grain growth by reducing the mobility advantage of abnormal grains. In addition, the fast precipitate coarsening rate tends to more quickly transform abnormal grain growth into normal grain growth by inducing the active growth of grains adjacent to the abnormal grains in the early stage. Therefore, the present study demonstrates that the time dependence of the pinning pressure of precipitates is a critical factor that determines the grain growth mode.

Analysis of late toxicity associated with external beam radiation therapy for prostate cancer with uniform setting of classical 4-field 70 Gy in 35 fractions: a survey study by the Osaka Urological Tumor Radiotherapy Study Group.

PubMed

Yoshioka, Yasuo; Suzuki, Osamu; Nishimura, Kazuo; Inoue, Hitoshi; Hara, Tsuneo; Yoshida, Ken; Imai, Atsushi; Tsujimura, Akira; Nonomura, Norio; Ogawa, Kazuhiko

2013-01-01

We aimed to analyse late toxicity associated with external beam radiation therapy (EBRT) for prostate cancer using uniform dose-fractionation and beam arrangement, with the focus on the effect of 3D (CT) simulation and portal field size. We collected data concerning patients with localized prostate adenocarcinoma who had been treated with EBRT at five institutions in Osaka, Japan, between 1998 and 2006. All had been treated with 70 Gy in 35 fractions, using the classical 4-field technique with gantry angles of 0°, 90°, 180° and 270°. Late toxicity was evaluated strictly in terms of the Common Terminology Criteria for Adverse Events Version 4.0. In total, 362 patients were analysed, with a median follow-up of 4.5 years (range 1.0-11.6). The 5-year overall and cause-specific survival rates were 93% and 96%, respectively. The mean ± SD portal field size in the right-left, superior-inferior, and anterior-posterior directions was, respectively, 10.8 ± 1.1, 10.2 ± 1.0 and 8.8 ± 0.9 cm for 2D simulation, and 8.4 ± 1.2, 8.2 ± 1.0 and 7.7 ± 1.0 cm for 3D simulation (P < 0.001). No Grade 4 or 5 late toxicity was observed. The actuarial 5-year Grade 2-3 genitourinary and gastrointestinal (GI) late toxicity rates were 6% and 14%, respectively, while the corresponding late rectal bleeding rate was 23% for 2D simulation and 7% for 3D simulation (P < 0.001). With a uniform setting of classical 4-field 70 Gy/35 fractions, the use of CT simulation and the resultant reduction in portal field size were significantly associated with reduced late GI toxicity, especially with less rectal bleeding.

Cascaded discrimination of normal, abnormal, and confounder classes in histopathology: Gleason grading of prostate cancer

PubMed Central

2012-01-01

Background Automated classification of histopathology involves identification of multiple classes, including benign, cancerous, and confounder categories. The confounder tissue classes can often mimic and share attributes with both the diseased and normal tissue classes, and can be particularly difficult to identify, both manually and by automated classifiers. In the case of prostate cancer, they may be several confounding tissue types present in a biopsy sample, posing as major sources of diagnostic error for pathologists. Two common multi-class approaches are one-shot classification (OSC), where all classes are identified simultaneously, and one-versus-all (OVA), where a “target” class is distinguished from all “non-target” classes. OSC is typically unable to handle discrimination of classes of varying similarity (e.g. with images of prostate atrophy and high grade cancer), while OVA forces several heterogeneous classes into a single “non-target” class. In this work, we present a cascaded (CAS) approach to classifying prostate biopsy tissue samples, where images from different classes are grouped to maximize intra-group homogeneity while maximizing inter-group heterogeneity. Results We apply the CAS approach to categorize 2000 tissue samples taken from 214 patient studies into seven classes: epithelium, stroma, atrophy, prostatic intraepithelial neoplasia (PIN), and prostate cancer Gleason grades 3, 4, and 5. A series of increasingly granular binary classifiers are used to split the different tissue classes until the images have been categorized into a single unique class. Our automatically-extracted image feature set includes architectural features based on location of the nuclei within the tissue sample as well as texture features extracted on a per-pixel level. The CAS strategy yields a positive predictive value (PPV) of 0.86 in classifying the 2000 tissue images into one of 7 classes, compared with the OVA (0.77 PPV) and OSC approaches (0.76 PPV). Conclusions Use of the CAS strategy increases the PPV for a multi-category classification system over two common alternative strategies. In classification problems such as histopathology, where multiple class groups exist with varying degrees of heterogeneity, the CAS system can intelligently assign class labels to objects by performing multiple binary classifications according to domain knowledge. PMID:23110677

Comparison of Digital Rectal Examination and Serum Prostate Specific Antigen in the Early Detection of Prostate Cancer: Results of a Multicenter Clinical Trial of 6,630 Men.

PubMed

Catalona, William J; Richie, Jerome P; Ahmann, Frederick R; Hudson, M'Liss A; Scardino, Peter T; Flanigan, Robert C; DeKernion, Jean B; Ratliff, Timothy L; Kavoussi, Louis R; Dalkin, Bruce L; Waters, W Bedford; MacFarlane, Michael T; Southwick, Paula C

2017-02-01

To compare the efficacy of digital rectal examination and serum prostate specific antigen (PSA) in the early detection of prostate cancer, we conducted a prospective clinical trial at 6 university centers of 6,630 male volunteers 50 years old or older who underwent PSA determination (Hybritech Tandom-E or Tandem-R assays) and digital rectal examination. Quadrant biopsies were performed if the PSA level was greater than 4 μg./l. or digital rectal examination was suspicious, even if transrectal ultrasonography revealed no areas suspicious for cancer. The results showed that 15% of the men had a PSA level of greater than 4 μg./l., 15% had a suspicious digital rectal examination and 26% had suspicious findings on either or both tests. Of 1,167 biopsies performed cancer was detected in 264. PSA detected significantly more tumors (82%, 216 of 264 cancers) than digital rectal examination (55%, 146 of 264, p = 0.001). The cancer detection rate was 3.2% for digital rectal examination, 4.6% for PSA and 5.8% for the 2 methods combined. Positive predictive value was 32% for PSA and 21% for digital rectal examination. Of 160 patients who underwent radical prostatectomy and pathological staging 114 (71%) had organ confined cancer: PSA detected 85 (75%) and digital rectal examination detected 64 (56%, p = 0.003). Use of the 2 methods in combination increased detection of organ confined disease by 78% (50 of 64 cases) over digital rectal examination alone. If the performance of a biopsy would have required suspicious transrectal ultrasonography findings, nearly 40% of the tumors would have been missed. We conclude that the use of PSA in conjunction with digital rectal examination enhances early prostate cancer detection. Prostatic biopsy should be considered if either the PSA level is greater than 4 μg./l. or digital rectal examination is suspicious for cancer, even in the absence of abnormal transrectal ultrasonography findings. Copyright © 1994 American Urological Association, Inc. Published by Elsevier Inc. All rights reserved.

Cost-effectiveness of prostate cancer screening: a simulation study based on ERSPC data.

PubMed

Heijnsdijk, E A M; de Carvalho, T M; Auvinen, A; Zappa, M; Nelen, V; Kwiatkowski, M; Villers, A; Páez, A; Moss, S M; Tammela, T L J; Recker, F; Denis, L; Carlsson, S V; Wever, E M; Bangma, C H; Schröder, F H; Roobol, M J; Hugosson, J; de Koning, H J

2015-01-01

The results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial showed a statistically significant 29% prostate cancer mortality reduction for the men screened in the intervention arm and a 23% negative impact on the life-years gained because of quality of life. However, alternative prostate-specific antigen (PSA) screening strategies for the population may exist, optimizing the effects on mortality reduction, quality of life, overdiagnosis, and costs. Based on data of the ERSPC trial, we predicted the numbers of prostate cancers diagnosed, prostate cancer deaths averted, life-years and quality-adjusted life-years (QALY) gained, and cost-effectiveness of 68 screening strategies starting at age 55 years, with a PSA threshold of 3, using microsimulation modeling. The screening strategies varied by age to stop screening and screening interval (one to 14 years or once in a lifetime screens), and therefore number of tests. Screening at short intervals of three years or less was more cost-effective than using longer intervals. Screening at ages 55 to 59 years with two-year intervals had an incremental cost-effectiveness ratio of $73000 per QALY gained and was considered optimal. With this strategy, lifetime prostate cancer mortality reduction was predicted as 13%, and 33% of the screen-detected cancers were overdiagnosed. When better quality of life for the post-treatment period could be achieved, an older age of 65 to 72 years for ending screening was obtained. Prostate cancer screening can be cost-effective when it is limited to two or three screens between ages 55 to 59 years. Screening above age 63 years is less cost-effective because of loss of QALYs because of overdiagnosis. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tamura, K; Araki, F; Ohno, T

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. Photonmore » 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.« less

Using manual prostate contours to enhance deformable registration of endorectal MRI.

PubMed

Cheung, M R; Krishnan, K

2012-10-01

Endorectal MRI provides detailed images of the prostate anatomy and is useful for radiation treatment planning. Here we describe a Demons field-initialized B-spline deformable registration of prostate MRI. T2-weighted endorectal MRIs of five patients were used. The prostate and the tumor of each patient were manually contoured. The planning MRIs and their segmentations were simulated by warping the corresponding endorectal MRIs using thin plate spline (TPS). Deformable registration was initialized using the deformation field generated using Demons algorithm to map the deformed prostate MRI to the non-deformed one. The solution was refined with B-Spline registration. Volume overlap similarity was used to assess the accuracy of registration and to suggest a minimum margin to account for the registration errors. Initialization using Demons algorithm took about 15 min on a computer with 2.8 GHz Intel, 1.3 GB RAM. Refinement B-spline registration (200 iterations) took less than 5 min. Using the synthetic images as the ground truth, at zero margin, the average (S.D.) 98 (±0.4)% for prostate coverage was 97 (±1)% for tumor. The average (±S.D.) treatment margin required to cover the entire prostate was 1.5 (±0.2)mm. The average (± S.D.) treatment margin required to cover the tumor was 0.7 (±0.1)mm. We also demonstrated the challenges in registering an in vivo deformed MRI to an in vivo non-deformed MRI. We here present a deformable registration scheme that can overcome large deformation. This platform is expected to be useful for prostate cancer radiation treatment planning. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Flexible proton 3D MR spectroscopic imaging of the prostate with low-power adiabatic pulses for volume selection and spiral readout.

PubMed

Steinseifer, Isabell K; Philips, Bart W J; Gagoski, Borjan; Weiland, Elisabeth; Scheenen, Tom W J; Heerschap, Arend

2017-03-01

Cartesian k-space sampling in three-dimensional magnetic resonance spectroscopic imaging (MRSI) of the prostate limits the selection of voxel size and acquisition time. Therefore, large prostates are often scanned at reduced spatial resolutions to stay within clinically acceptable measurement times. Here we present a semilocalized adiabatic selective refocusing (sLASER) sequence with gradient-modulated offset-independent adiabatic (GOIA) refocusing pulses and spiral k-space acquisition (GOIA-sLASER-Spiral) for fast prostate MRSI with enhanced resolution and extended matrix sizes. MR was performed at 3 tesla with an endorectal receive coil. GOIA-sLASER-Spiral at an echo time (TE) of 90 ms was compared to a point-resolved spectroscopy sequence (PRESS) with weighted, elliptical phase encoding at an TE of 145 ms using simulations and measurements of phantoms and patients (n = 9). GOIA-sLASER-Spiral acquisition allows prostate MR spectra to be obtained in ∼5 min with a quality comparable to those acquired with a common Cartesian PRESS protocol in ∼9 min, or at an enhanced spatial resolution showing more precise tissue allocation of metabolites. Extended field of views (FOVs) and matrix sizes for large prostates are possible without compromising spatial resolution or measurement time. The flexibility of spiral sampling enables prostate MRSI with a wide range of resolutions and FOVs without undesirable increases in acquisition times, as in Cartesian encoding. This approach is suitable for routine clinical exams of prostate metabolites. Magn Reson Med 77:928-935, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

A dosimetric comparison of {sup 169}Yb versus {sup 192}Ir for HDR prostate brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lymperopoulou, G.; Papagiannis, P.; Sakelliou, L.

2005-12-15

For the purpose of evaluating the use of {sup 169}Yb for prostate High Dose Rate brachytherapy (HDR), a hypothetical {sup 169}Yb source is assumed with the exact same design of the new microSelectron source replacing the {sup 192}Ir active core by pure {sup 169}Yb metal. Monte Carlo simulation is employed for the full dosimetric characterization of both sources and results are compared following the AAPM TG-43 dosimetric formalism. Monte Carlo calculated dosimetry results are incorporated in a commercially available treatment planning system (SWIFT{sup TM}), which features an inverse treatment planning option based on a multiobjective dose optimization engine. The qualitymore » of prostate HDR brachytherapy using the real {sup 192}Ir and hypothetical {sup 169}Yb source is compared in a comprehensive analysis of different prostate implants in terms of the multiobjective dose optimization solutions as well as treatment quality indices such as Dose Volume Histograms (DVH) and the Conformal Index (COIN). Given that scattering overcompensates for absorption in intermediate photon energies and distances in the range of interest to prostate HDR brachytherapy, {sup 169}Yb proves at least equivalent to {sup 192}Ir irrespective of prostate volume. This has to be evaluated in view of the shielding requirements for the {sup 169}Yb energies that are minimal relative to that for {sup 192}Ir.« less

Further Developments in Microwave Ablation of Prostate Cells

NASA Technical Reports Server (NTRS)

Arndt, G. Dickey; Ngo, Phong

2005-01-01

A report presents additional information about the subject matter of Microwave Treatment of Prostate Cancer and Hyperplasia (MSC-23049), NASA Tech Briefs, Vol. 29, No. 6 (June 2005), page 62. To recapitulate: the basic idea is to use microwaves to heat and thereby kill small volumes of unhealthy prostate tissue. The prostate is irradiated with microwaves from one or more antennas positioned near the prostate by means of catheters inserted in the urethra and/or colon. The microwave frequency, power, and exposure time, phasing, positions, and orientations of the antennas may be chosen to obtain the desired temperature rise in the heated region and to ensure that the location and extent of the heated region coincides with the region to be treated to within a few millimeters. Going beyond the description in the cited previous article, the report includes a diagram that illustrates typical placement of urethra and colon antenna catheters and presents results of computationally simulated prostate-heating profiles for several different combinations of antenna arrangements, frequencies, and delivered- energy levels as well as experimental results within phantom materials. The advantage of the two-antenna technology is that the heat generated at each antenna is significantly reduced from that associated with only one antenna. The microwave energy radiated from each antenna is focused at the tumor center by adjusting the phasing of the irradiated microwave signal from the antennas.

Clinical Utility of Urinary CD90 as a Biomarker for Prostate Cancer Detection — EDRN Public Portal

Cancer.gov

Tumor-associated stromal cells differ from normal gland-associated stromal cells in gene expression. Genes up-regulated in these stromal cells are potential cancer biomarkers, especially those encoding secreted or extracellular proteins. These proteins might be detected in urine. CD90/THY1 is one such candidate. A clinical test based on urinary CD90 would be useful in reducing the number of unnecessary biopsies done because of abnormal serum PSA and/or DRE finding. Elevated CD90 protein is found in tumor tissue and urine.

Müllerian duct cyst: diagnosis with MR imaging.

PubMed

Thurnher, S; Hricak, H; Tanagho, E A

1988-07-01

The value of magnetic resonance (MR) imaging in diagnosing clinically suspected müllerian duct cysts was assessed in six patients. MR imaging correctly demonstrated the abnormality to be intraprostatic, consistent with the diagnosis of müllerian duct cysts in four patients, and allowed the diagnosis to be excluded in the other two. The demonstration of prostatic zonal anatomy, the ability to obtain direct images in all three orthogonal planes, and a large field of view make MR imaging valuable in the study of suspected müllerian duct cysts.

The Role of Polycomb Group Gene BMI-1 in the Development of Prostate Cancer

DTIC Science & Technology

2009-09-01

17. Fu M, Wang C, Li Z, Sakamaki T, Pestell RG. Minireview: Cyclin D1: normal and abnormal functions. Endocrinology. 2004 Dec;145(12):5439-47. 18...connecting development to breast cancer. Cell Cycle. 2004 Feb;3(2):145-8. 32. Wang C, Li Z, Fu M, Bouras T, Pestell RG. Signal transduction mediated by...Ferzli G, Johnson K, Fricke S, Diba F, Kallakury B, Ohanyerenwa C, Chen M, Ostrowski M, Hung MC, Rabbani SA, Datar R, Cote R, Pestell R, Albanese C

The Mechanosensitive Ca2+ Channel as a Central Regular of Prostate Tumor Cell Migration and Invasiveness

DTIC Science & Technology

2009-01-01

sibly explain why the absence of dystrophin in Duchenne muscular dystrophic muscle results in TRPC1 channels being abnormally gated open (see Sect...135 7/30/2007 6:35:10 PM 136 O.P. Hamill, R. Maroto 7.6.1.4 TRPC1 in Muscular Dystrophy Both TRPC1 and MscCa are expressed in skeletal muscle and...both have been implicated in the muscular degeneration that occurs in Duchenne muscular dystro- phy (DMD). In particular, muscle fibers from the mdx

Dosimetric and workflow evaluation of first commercial synthetic CT software for clinical use in pelvis

NASA Astrophysics Data System (ADS)

Tyagi, Neelam; Fontenla, Sandra; Zhang, Jing; Cloutier, Michelle; Kadbi, Mo; Mechalakos, Jim; Zelefsky, Michael; Deasy, Joe; Hunt, Margie

2017-04-01

To evaluate a commercial synthetic CT (syn-CT) software for use in prostate radiotherapy. Twenty-five prostate patients underwent CT and MR simulation scans in treatment position on a 3T MR scanner. A commercially available MR protocol was used that included a T2w turbo spin-echo sequence for soft-tissue contrast and a dual echo 3D mDIXON fast field echo (FFE) sequence for generating syn-CT. A dual-echo 3D FFE B 0 map was used for patient-induced susceptibility distortion analysis and a new 3D balanced-FFE sequence was evaluated for identification of implanted gold fiducial markers and subsequent image-guidance during radiotherapy delivery. Tissues were classified as air, adipose, water, trabecular/spongy bone and compact/cortical bone and assigned bulk HU values. The accuracy of syn-CT for treatment planning was analyzed by transferring the structures and plan from planning CT to syn-CT and recalculating the dose. Accuracy of localization at the treatment machine was evaluated by comparing registration of kV radiographs to either digitally reconstructed radiographs (DRRs) generated from syn-CT or traditional DRRs generated from the planning CT. Similarly, accuracy of setup using CBCT and syn-CT was compared to that using the planning CT. Finally, a MR-only simulation workflow was established and end-to-end testing was completed on five patients undergoing MR-only simulation. Dosimetric comparison between the original CT and syn-CT plans was within 0.5% on average for all structures. The de-novo optimized plans on the syn-CT met institutional clinical objectives for target and normal structures. Patient-induced susceptibility distortion based on B 0 maps was within 1 mm and 0.5 mm in the body and prostate respectively. DRR and CBCT localization based on MR-localized fiducials showed a standard deviation of  <1 mm. End-to-end testing and MR simulation workflow was successfully validated. MRI derived synthetic CT can be successfully used for a MR-only planning and treatment for prostate radiotherapy.

Thermal dosimetry analysis combined with patient-specific thermal modeling of clinical interstitial ultrasound hyperthermia integrated within HDR brachytherapy for treatment of locally advanced prostate cancer

NASA Astrophysics Data System (ADS)

Salgaonkar, Vasant A.; Wootton, Jeff; Prakash, Punit; Scott, Serena; Hsu, I. C.; Diederich, Chris J.

2017-03-01

This study presents thermal dosimetry analysis from clinical treatments where ultrasound hyperthermia (HT) was administered following high-dose rate (HDR) brachytherapy treatment for locally advanced prostate cancer as part of a clinical pilot study. HT was administered using ultrasound applicators from within multiple 13-g brachytherapy catheters implanted along the posterior periphery of the prostate. The heating applicators were linear arrays of sectored tubular transducers (˜7 MHz), with independently powered array elements enabling energy deposition with 3D spatial control. Typical heat treatments employed time-averaged peak acoustic intensities of 1 - 3 W/cm2 and lasted for 60 - 70 minutes. Throughout the treatments, temperatures at multiple points were monitored using multi-junction thermocouples, placed within available brachytherapy catheters throughout mid-gland prostate and identified as the hyperthermia target volume (HTV). Clinical constraints allowed placement of 8 - 12 thermocouple sensors in the HTV and patient-specific 3D thermal modeling based on finite element methods (FEM) was used to supplement limited thermometry. Patient anatomy, heating device positions, orientations, and thermometry junction locations were obtained from patient CT scans and HDR and hyperthermia planning software. The numerical models utilized the applied power levels recorded during the treatments. Tissue properties such as perfusion and acoustic absorption were varied within physiological ranges such that squared-errors between measured and simulated temperatures were minimized. This data-fitting was utilized for 6 HT treatments to estimate volumetric temperature distributions achieved in the HTV and surrounding anatomy devoid of thermocouples. For these treatments, the measured and simulated T50 values in the hyperthermia target volume (HTV) were between 40.1 - 43.9 °C and 40.3 - 44.9 °C, respectively. Maximum temperatures between 46.8 - 49.8 °C were measured during these treatments and the corresponding range obtained from simulation was 47.3 - 51.1 °C. Based on the simulations, the maximum temperatures in the bladder and the rectum were below 41.7 °C and 41.1 °C, respectively.

Detection and clearance of prostate cells subsequent to ultrasound-guided needle biopsy as determined by multiplex nested reverse transcription polymerase chain reaction assay.

PubMed

Price, D K; Clontz, D R; Woodard, W L; Kaufman, J S; Daniels, J M; Stolzenberg, S J; Teigland, C M

1998-08-01

To determine if circulating prostate cells are detectable subsequent to transrectal ultrasound (TRUS)-guided biopsy, and if so, whether cells remain in circulation for up to 4 weeks. Blood samples were drawn from 90 patients with elevated serum prostate-specific antigen (PSA) levels and/or abnormal digital rectal examination. Two samples were drawn from all patients immediately prior to TRUS and 30 minutes postbiopsy. Blood samples were also obtained 1 week postbiopsy from 83 patients, and 1 month postbiopsy from 61 patients. Multiplex nested reverse transcription polymerase chain reaction assay (RT-PCR) for PSA and prostate-specific membrane antigen (PSM) was performed on total ribonucleic acid (RNA) from each sample. Results were reported as positive if at least one of the targets was detected. Of 45 patients with biopsy-proven adenocarcinoma, 22 were RT-PCR positive prebiopsy and all remained positive 30 minutes postbiopsy. Of 23 patients with adenocarcinoma who were RT-PCR negative prebiopsy, 5 (22%) converted to positive 30 minutes postbiopsy (P < 0.001). Four of these 5 patients returned to negative after 1 week or 1 month. Of 45 patients without cancer at biopsy, 32 were RT-PCR negative prebiopsy and 6 (19%) converted to positive 30 minutes postbiopsy (P < 0.001). Although four of six available samples were still positive at 1 week, all four samples available 1 month postbiopsy were negative. Detection of circulating prostate cells subsequent to biopsy occurred in 11 of 55 (20%) previously RT-PCR negative patients, a proportion twice that reported in the literature. We attribute this higher proportion to the simultaneous detection of PSA and PSM mRNA in our multiplex assay. Conversion rates were similar in patients regardless of biopsy result. Testing of serial postbiopsy blood demonstrates clearing of these cells by 4 weeks in most patients.

O-Glycosylation-mediated signaling circuit drives metastatic castration-resistant prostate cancer.

PubMed

Tzeng, Sheue-Fen; Tsai, Chin-Hsien; Chao, Tai-Kuang; Chou, Yu-Ching; Yang, Yu-Chih; Tsai, Mong-Hsun; Cha, Tai-Lung; Hsiao, Pei-Wen

2018-06-15

Disseminated castration-resistant prostate cancer (CRPC) is a common disease in men that is characterized by limited survival and resistance to androgen-deprivation therapy. The increase in human epidermal growth factor receptor 2 (HER2) signaling contributes to androgen receptor activity in a subset of patients with CRPC; however, enigmatically, HER2-targeted therapies have demonstrated a lack of efficacy in patients with CRPC. Aberrant glycosylation is a hallmark of cancer and involves key processes that support cancer progression. Using transcriptomic analysis of prostate cancer data sets, histopathologic examination of clinical specimens, and in vivo experiments of xenograft models, we reveal in this study a coordinated increase in glycan-binding protein, galectin-4, specific glycosyltransferases of core 1 synthase, glycoprotein- N-acetylgalactosamine 3-β-galactosyltransferase 1 (C1GALT1) and ST3 beta-galactoside α-2,3-sialyltransferase 1 (ST3GAL1), and resulting mucin-type O-glycans during the progression of CRPC. Furthermore, galectin-4 engaged with C1GALT1-dependent O-glycans to promote castration resistance and metastasis by activating receptor tyrosine kinase signaling and cancer cell stemness properties mediated by SRY-box 9 (SOX9). This galectin-glycan interaction up-regulated the MYC-dependent expression of C1GALT1 and ST3GAL1, which altered cellular mucin-type O-glycosylation to allow for galectin-4 binding. In clinical prostate cancer, high-level expression of C1GALT1 and galectin-4 together predict poor overall survival compared with low-level expression of C1GALT1 and galectin-4. In summary, MYC regulates abnormal O-glycosylation, thus priming cells for binding to galectin-4 and downstream signaling, which promotes castration resistance and metastasis.-Tzeng, S.-F., Tsai, C.-H., Chao, T.-K., Chou, Y.-C., Yang, Y.-C., Tsai, M.-H., Cha, T.-L., Hsiao, P.-W. O-Glycosylation-mediated signaling circuit drives metastatic castration-resistant prostate cancer.

An ESIPT fluorescent probe sensitive to protein α-helix structures.

PubMed

Jiang, Nan; Yang, Chanli; Dong, Xiongwei; Sun, Xianglang; Zhang, Dan; Liu, Changlin

2014-07-28

A large majority of membrane proteins have one or more transmembrane regions consisting of α-helices. Membrane protein levels differ from one type of cell to another, and the expression of membrane proteins also changes from normal to diseased cells. For example, prostate cancer cells have been reported to have downregulated expression of membrane proteins, including zinc transporters, compared with normal prostate cells. These reports inspired us to design a fluorescence probe sensitive to protein α-helical structures to discriminate individual prostate cancer cells from normal ones. A benzazole derivative ( in this study) was observed to emit strong fluorescence resulting from an excited-state intramolecular proton transfer (ESIPT) in protein α-helical environments. The intensity of ESIPT fluorescence of was observed to be positively correlated with the α-helix content of proteins. The molecular docking simulation suggested that it had low energy for the binding of to proteins when the binding sites were localized within the α-helical regions of protein via H-bonds. Furthermore, was found to be localized in cell membranes through binding to transmembrane α-helical regions of membrane proteins, and was capable of probing differences in the α-helix contents of membrane proteins between normal and cancerous prostate cells through changes in the ESIPT emission intensity. These results indicated that could distinguish individual prostate cancer cells from normal ones, as the changes in the ESIPT fluorescence intensity of could reflect the regulation in expression of the membrane proteins including zinc transporters. This recognition strategy of individual prostate cancer cells might contribute to early diagnosis techniques for prostate cancer.

Dosimetric and geometric evaluation of a hybrid strategy of offline adaptive planning and online image guidance for prostate cancer radiotherapy

PubMed Central

Liu, Han; Wu, Qiuwen

2011-01-01

For prostate cancer patients, online image-guided (IG) radiotherapy has been widely used in clinic to correct the translational inter-fractional motion at each treatment fraction. For uncertainties that cannot be corrected online, such as rotation and deformation of the target volume, margins are still required to be added to the clinical target volume (CTV) for the treatment planning. Offline adaptive radiotherapy has been implemented to optimize the treatment for each individual patient based on the measurements at early stages of treatment process. It has been shown that offline adaptive radiotherapy can effectively reduce the required margin. Recently a hybrid strategy of offline adaptive replanning and online IG was proposed and the geometric evaluation was performed. It was found that the planning margins can be further reduced by 1–2 mm compared to online IG only strategy. The purpose of this study was to investigate the dosimetric benefits of such hybrid strategy on the target and organs at risk (OARs). A total of 420 repeated helical computed tomography (HCT) scans from 28 patients were included in the study. Both low-risk patients (LRP, CTV = prostate) and intermediate-risk patients (IRP, CTV = prostate + seminal vesicles, SV) were included in the simulation. Two registration methods, based on center-of-mass (COM) shift of prostate only and prostate plus SV, were performed for IRP. The intensity modulated radiotherapy (IMRT) was used in the simulation. Criteria on both cumulative dose and fractional doses were evaluated. Furthermore, the geometric evaluation was extended to investigate the optimal number of fractions necessary to construct the internal target volume (ITV) for the hybrid strategy. The dosimetric margin improvement was smaller than its geometric counterpart and was in the range of 0 mm to 1 mm. The optimal number of fractions necessary for the ITV construction is 2 for LRP and 3–4 for IRP in a hypofractionation protocol. A new cumulative index of target volume (CITV) was proposed for the evaluation of adaptive radiotherapy strategies, and it was found that it had the advantages over other indices in evaluating different adaptive radiotherapy strategies. PMID:21772083

Dosimetric and geometric evaluation of a hybrid strategy of offline adaptive planning and online image guidance for prostate cancer radiotherapy.

PubMed

Liu, Han; Wu, Qiuwen

2011-08-07

For prostate cancer patients, online image-guided (IG) radiotherapy has been widely used in clinic to correct the translational inter-fractional motion at each treatment fraction. For uncertainties that cannot be corrected online, such as rotation and deformation of the target volume, margins are still required to be added to the clinical target volume (CTV) for the treatment planning. Offline adaptive radiotherapy has been implemented to optimize the treatment for each individual patient based on the measurements at early stages of treatment process. It has been shown that offline adaptive radiotherapy can effectively reduce the required margin. Recently a hybrid strategy of offline adaptive replanning and online IG was proposed and the geometric evaluation was performed. It was found that the planning margins can further be reduced by 1-2 mm compared to online IG only strategy. The purpose of this study was to investigate the dosimetric benefits of such a hybrid strategy on the target and organs at risk. A total of 420 repeated helical computed tomography scans from 28 patients were included in the study. Both low-risk patients (LRP, CTV = prostate) and intermediate-risk patients (IRP, CTV = prostate + seminal vesicles, SV) were included in the simulation. Two registration methods, based on center-of-mass shift of prostate only and prostate plus SV, were performed for IRP. The intensity-modulated radiotherapy was used in the simulation. Criteria on both cumulative and fractional doses were evaluated. Furthermore, the geometric evaluation was extended to investigate the optimal number of fractions necessary to construct the internal target volume (ITV) for the hybrid strategy. The dosimetric margin improvement was smaller than its geometric counterpart and was in the range of 0-1 mm. The optimal number of fractions necessary for the ITV construction is 2 for LRPs and 3-4 for IRPs in a hypofractionation protocol. A new cumulative index of target volume was proposed for the evaluation of adaptive radiotherapy strategies, and it was found that it had the advantages over other indices in evaluating different adaptive radiotherapy strategies.

SU-C-17A-03: Evaluation of Deformable Image Registration Methods Between MRI and CT for Prostate Cancer Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wen, N; Glide-Hurst, C; Zhong, H

2014-06-15

Purpose: We evaluated the performance of two commercially available and one open source B-Spline deformable image registration (DIR) algorithms between T2-weighted MRI and treatment planning CT using the DICE indices. Methods: CT simulation (CT-SIM) and MR simulation (MR-SIM) for four prostate cancer patients were conducted on the same day using the same setup and immobilization devices. CT images (120 kVp, 500 mAs, voxel size = 1.1x1.1x3.0 mm3) were acquired using an open-bore CT scanner. T2-weighted Turbo Spine Echo (T2W-TSE) images (TE/TR/α = 80/4560 ms/90°, voxel size = 0.7×0.7×2.5 mm3) were scanned on a 1.0T high field open MR-SIM. Prostates, seminalmore » vesicles, rectum and bladders were delineated on both T2W-TSE and CT images by the attending physician. T2W-TSE images were registered to CT images using three DIR algorithms, SmartAdapt (Varian), Velocity AI (Velocity) and Elastix (Klein et al 2010) and contours were propagated. DIR results were evaluated quantitatively or qualitatively by image comparison and calculating organ DICE indices. Results: Significant differences in the contours of prostate and seminal vesicles were observed between MR and CT. On average, volume changes of the propagated contours were 5%, 2%, 160% and 8% for the prostate, seminal vesicles, bladder and rectum respectively. Corresponding mean DICE indices were 0.7, 0.5, 0.8, and 0.7. The intraclass correlation coefficient (ICC) was 0.9 among three algorithms for the Dice indices. Conclusion: Three DIR algorithms for CT/MR registration yielded similar results for organ propagation. Due to the different soft tissue contrasts between MRI and CT, organ delineation of prostate and SVs varied significantly, thus efforts to develop other DIR evaluation metrics are warranted. Conflict of interest: Submitting institution has research agreements with Varian Medical System and Philips Healthcare.« less

SU-C-17A-02: Sirius MRI Markers for Prostate Post-Implant Assessment: MR Protocol Development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, T; Wang, J; Kudchadker, R

Purpose: Currently, CT is used to visualize prostate brachytherapy sources, at the expense of accurate structure contouring. MRI is superior to CT for anatomical delineation, but the sources appear as voids on MRI images. Previously we have developed Sirius MRI markers (C4 Imaging) to replace spacers to assist source localization on MRI images. Here we develop an MRI pulse sequence protocol that enhances the signal of these markers to enable MRI-only post-implant prostate dosimetric analysis. Methods: To simulate a clinical scenario, a CIRS multi-modality prostate phantom was implanted with 66 markers and 86 sources. The implanted phantom was imaged onmore » both 1.5T and 3.0T GE scanners under various conditions, different pulse sequences (2D fast spin echo [FSE], 3D balanced steadystate free precession [bSSFP] and 3D fast spoiled gradient echo [FSPGR]), as well as varying amount of padding to simulate various patient sizes and associated signal fall-off from the surface coil elements. Standard FSE sequences from the current clinical protocols were also evaluated. Marker visibility, marker size, intra-marker distance, total scan time and artifacts were evaluated for various combinations of echo time, repetition time, flip angle, number of excitations, bandwidth, slice thickness and spacing, fieldof- view, frequency/phase encoding steps and frequency direction. Results: We have developed a 3D FSPGR pulse sequence that enhances marker signal and ensures the integrity of the marker shape while maintaining reasonable scan time. For patients contraindicated for 3.0T, we have also developed a similar sequence for 1.5T scanners. Signal fall-off with distance from prostate to coil can be compensated mainly by decreasing bandwidth. The markers are not visible using standard FSE sequences. FSPGR sequences are more robust for consistent marker visualization as compared to bSSFP sequences. Conclusion: The developed MRI pulse sequence protocol for Sirius MRI markers assists source localization to enable MRIonly post-implant prostate dosimetric analysis. S.J. Frank is a co-founder of C4 Imaging (manufactures the MRI markers)« less

Non-Invasive Prostate Cancer Characterization with Diffusion-Weighted MRI: Insight from In silico Studies of a Transgenic Mouse Model

PubMed Central

Hill, Deborah K.; Heindl, Andreas; Zormpas-Petridis, Konstantinos; Collins, David J.; Euceda, Leslie R.; Rodrigues, Daniel N.; Moestue, Siver A.; Jamin, Yann; Koh, Dow-Mu; Yuan, Yinyin; Bathen, Tone F.; Leach, Martin O.; Blackledge, Matthew D.

2017-01-01

Diffusion-weighted magnetic resonance imaging (DWI) enables non-invasive, quantitative staging of prostate cancer via measurement of the apparent diffusion coefficient (ADC) of water within tissues. In cancer, more advanced disease is often characterized by higher cellular density (cellularity), which is generally accepted to correspond to a lower measured ADC. A quantitative relationship between tissue structure and in vivo measurements of ADC has yet to be determined for prostate cancer. In this study, we establish a theoretical framework for relating ADC measurements with tissue cellularity and the proportion of space occupied by prostate lumina, both of which are estimated through automatic image processing of whole-slide digital histology samples taken from a cohort of six healthy mice and nine transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. We demonstrate that a significant inverse relationship exists between ADC and tissue cellularity that is well characterized by our model, and that a decrease of the luminal space within the prostate is associated with a decrease in ADC and more aggressive tumor subtype. The parameters estimated from our model in this mouse cohort predict the diffusion coefficient of water within the prostate-tissue to be 2.18 × 10−3 mm2/s (95% CI: 1.90, 2.55). This value is significantly lower than the diffusion coefficient of free water at body temperature suggesting that the presence of organelles and macromolecules within tissues can drastically hinder the random motion of water molecules within prostate tissue. We validate the assumptions made by our model using novel in silico analysis of whole-slide histology to provide the simulated ADC (sADC); this is demonstrated to have a significant positive correlation with in vivo measured ADC (r2 = 0.55) in our mouse population. The estimation of the structural properties of prostate tissue is vital for predicting and staging cancer aggressiveness, but prostate tissue biopsies are painful, invasive, and are prone to complications such as sepsis. The developments made in this study provide the possibility of estimating the structural properties of prostate tissue via non-invasive virtual biopsies from MRI, minimizing the need for multiple tissue biopsies and allowing sequential measurements to be made for prostate cancer monitoring. PMID:29250485

Immunoendocrine abnormalities in the male reproductive system during experimental pulmonary tuberculosis.

PubMed

Ramos Robles, Brenda; Valdez, Ricardo A; Hernández, Uriel Juárez; Marquina Castillo, Brenda; Mata Espinosa, Dulce; Barrios Payan, Jorge; Hernández Pando, Rogelio; Romano, Marta C

2018-03-01

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that mainly affects the lungs. Along the course of pulmonary TB there are remarkable changes in the production of cytokines that cause endocrine changes. So far, it is not known the physiological and histological changes in the male reproductive system during pulmonary TB. To investigate whether pulmonary TB produces histological alterations of the BALB/c mice reproductive organs, as well as abnormalities in spermatogenesis, serum testosterone concentrations and expression of testicular cytokines. BALB/c mice were infected intratracheally with high dose Mtb strain H37Rv. Groups of six non infected and infected animals were euthanized on days 1, 3, 7, 14, 21, 28, 60, 90 and 120 post-infection. Bacillary loads were determined by counting colony forming units (CFUs) in lungs, testes, prostate and seminal vesicles. Histological sections were obtained from the same organs. Spermatozoids number and quality were assessed by spermatobioscopy. Serum testosterone concentrations were determined by radioimmunoanalysis (RIA) in control and infected mice in each time of sacrifice. Mtb only grew in lung tissue. Serum androgens showed a trend to decrease in the infected mice compared to the healthy animals, the difference turn into statistically significance at post infection day 120. The weight of the testis was not modified throughout the study, and no histopathological changes were found. However, we detected a significant decrease in the weight of the seminal vesicles and prostate starting at 28 days post-infection. Atrophy of the seminal vesicles and prostate epithelia were significant, beginning after 60 days of infection. Spermatobioscopy revealed hypospermia in the later stages of the disease. We have observed in the testes a local significant disbalance on the cytokine profile (increase of IL-6 and decrease of IL-10 and TGF-b levels) together with a very significant reduction of the body weight during late pulmonary TB. Pulmonary TB affects the histophysiology of the male reproductive system due to hormonal changes, an imbalance of pro-inflammatory cytokine profile, and a wasting syndrome during late disease. Copyright © 2018. Published by Elsevier Ltd.

Neurophysiological model of the normal and abnormal human pupil

NASA Technical Reports Server (NTRS)

Krenz, W.; Robin, M.; Barez, S.; Stark, L.

1985-01-01

Anatomical, experimental, and computer simulation studies were used to determine the structure of the neurophysiological model of the pupil size control system. The computer simulation of this model demonstrates the role played by each of the elements in the neurological pathways influencing the size of the pupil. Simulations of the effect of drugs and common abnormalities in the system help to illustrate the workings of the pathways and processes involved. The simulation program allows the user to select pupil condition (normal or an abnormality), specific site along the neurological pathway (retina, hypothalamus, etc.) drug class input (barbiturate, narcotic, etc.), stimulus/response mode, display mode, stimulus type and input waveform, stimulus or background intensity and frequency, the input and output conditions, and the response at the neuroanatomical site. The model can be used as a teaching aid or as a tool for testing hypotheses regarding the system.

The stem cell factor (SCF)/c-KIT signalling in testis and prostate cancer.

PubMed

Cardoso, Henrique J; Figueira, Marília I; Socorro, Sílvia

2017-12-01

The stem cell factor (SCF) is a cytokine that specifically binds the tyrosine kinase receptor c-KIT. The SCF/c-KIT interaction leads to receptor dimerization, activation of kinase activity and initiation of several signal transduction pathways that control cell proliferation, apoptosis, differentiation and migration in several tissues. The activity of SCF/c-KIT system is linked with the phosphatidylinositol 3-kinase (PI3-K), the Src, the Janus kinase/signal transducers and activators of transcription (JAK/STAT), the phospholipase-C (PLC-γ) and the mitogen-activated protein kinase (MAPK) pathways. Moreover, it has been reported that cancer cases display an overactivation of c-KIT due to the presence of gain-of-function mutations or receptor overexpression, which renders c-KIT a tempting target for cancer treatment. In the case of male cancers the most documented activated pathways are the PI3-K and Src, both enhancing abnormal cell proliferation. It is also known that the Src activity in prostate cancer cases depends on the presence of tr-KIT, the cytoplasmic truncated variant of c-KIT that is specifically expressed in tumour tissues and, thus, a very interesting target for drug development. The present review provides an overview of the signalling pathways activated by SCF/c-KIT and discusses the potential application of c-KIT inhibitors for treatment of testicular and prostatic cancers.

Acute progressive paravascular placoid neuroretinopathy with negative-type electroretinography in paraneoplastic retinopathy.

PubMed

Chen, Fred K; Chew, Avenell L; Zhang, Dan; Chen, Shang-Chih; Chelva, Enid; Chandrasekera, Erandi; Koay, Eleanor M H; Forrester, John; McLenachan, Samuel

2017-06-01

Paraneoplastic retinopathy can be the first manifestation of systemic malignancy. A subset of paraneoplastic retinopathy is characterized by negative-type electroretinography (ERG) without fundus abnormality. Here we describe the multimodal imaging and clinico-pathological correlation of a unique case of acute progressive paravascular placoid neuroretinopathy with suspected retinal depolarizing bipolar cell dysfunction preceding the diagnosis of metastatic small cell carcinoma of the prostate. ERG was performed according to the International Society for Clinical Electrophysiology of Vision standards. Imaging modalities included near-infrared reflectance, blue-light autofluorescence, fluorescein and indocyanine green angiographies, spectral domain optical coherence tomography, ultra-widefield colour and green-light autofluorescence imaging, microperimetry and adaptive optics imaging. Patient serum was screened for anti-retinal antibodies using western blotting. Immunostaining and histological analyses were performed on sections from human retinal tissues and a patient prostate biopsy. Serial multimodal retinal imaging, microperimetry and adaptive optics photography demonstrated a paravascular distribution of placoid lesions characterized by hyper-reflectivity within the outer nuclear layer resembling type 2 acute macular neuroretinopathy. There was no visible lesion within the inner nuclear layer despite electronegative-type ERG. Six months later, the patient presented with metastatic small cell carcinoma of the prostate. Tumour cells were immunopositive for glyceraldehyde-3-phosphate dehydrogenase, enolase and recoverin as well as neuroendocrine markers. The patient's serum reacted to cytoplasmic and nuclear antigens in the prostate biopsy and in human retina. Anti-retinal antibodies against several antigens were detected by both commercial and in-house western blots. A spectrum of autoreactive anti-retinal antibodies is associated with a unique phenotype of acute progressive paravascular placoid neuroretinopathy resulting in degeneration of photoreceptor cells, inner retinal dysfunction and classic electronegative ERG in paraneoplastic retinopathy. Detailed clinical, functional and immunological phenotyping of paraneoplastic retinopathy illustrated the complex mechanism of paraneoplastic syndrome.

Computerized planning of prostate cryosurgery using variable cryoprobe insertion depth.

PubMed

Rossi, Michael R; Tanaka, Daigo; Shimada, Kenji; Rabin, Yoed

2010-02-01

The current study presents a computerized planning scheme for prostate cryosurgery using a variable insertion depth strategy. This study is a part of an ongoing effort to develop computerized tools for cryosurgery. Based on typical clinical practices, previous automated planning schemes have required that all cryoprobes be aligned at a single insertion depth. The current study investigates the benefit of removing this constraint, in comparison with results based on uniform insertion depth planning as well as the so-called "pullback procedure". Planning is based on the so-called "bubble-packing method", and its quality is evaluated with bioheat transfer simulations. This study is based on five 3D prostate models, reconstructed from ultrasound imaging, and cryoprobe active length in the range of 15-35 mm. The variable insertion depth technique is found to consistently provide superior results when compared to the other placement methods. Furthermore, it is shown that both the optimal active length and the optimal number of cryoprobes vary among prostate models, based on the size and shape of the target region. Due to its low computational cost, the new scheme can be used to determine the optimal cryoprobe layout for a given prostate model in real time. Copyright 2008 Elsevier Inc. All rights reserved.

A clinical data validated mathematical model of prostate cancer growth under intermittent androgen suppression therapy

NASA Astrophysics Data System (ADS)

Portz, Travis; Kuang, Yang; Nagy, John D.

2012-03-01

Prostate cancer is commonly treated by a form of hormone therapy called androgen suppression. This form of treatment, while successful at reducing the cancer cell population, adversely affects quality of life and typically leads to a recurrence of the cancer in an androgen-independent form. Intermittent androgen suppression aims to alleviate some of these adverse affects by cycling the patient on and off treatment. Clinical studies have suggested that intermittent therapy is capable of maintaining androgen dependence over multiple treatment cycles while increasing quality of life during off-treatment periods. This paper presents a mathematical model of prostate cancer to study the dynamics of androgen suppression therapy and the production of prostate-specific antigen (PSA), a clinical marker for prostate cancer. Preliminary models were based on the assumption of an androgen-independent (AI) cell population with constant net growth rate. These models gave poor accuracy when fitting clinical data during simulation. The final model presented hypothesizes an AI population with increased sensitivity to low levels of androgen. It also hypothesizes that PSA production is heavily dependent on androgen. The high level of accuracy in fitting clinical data with this model appears to confirm these hypotheses, which are also consistent with biological evidence.

PEG spacer gel and adaptive planning vs single plan in external prostate radiotherapy—clinical dosimetry evaluation

PubMed Central

2015-01-01

Objective: Spacer gel is used to reduce the rectal dose in prostate radiotherapy. It is injected to increase the distance between the prostate and rectum. During the course of external radiotherapy treatment, physiological changes in rectal volume exist. When using polyethylene glycol material, such as DuraSeal® (Covidien, Mansfield, MA), gel resorption also occurs. Together, these factors alter the original dose plan distribution. Methods: External dose planning and calculations were simulated using images acquired from 10 patients who were treated with brachytherapy and gel. The CT series was taken relative to gel injection: pre 1 day, post 1 day, post 1 month and post 2 months. Adaptive planning was compared with a single plan. Results: Adaptive planning shows better results compared with the single plan used in the total treatment course; however, the effect is minor. Conclusion: Gel usage is clearly favourable to rectal DVH. Using adaptive planning with gel improves rectal DVH but is not necessary according to this study. Advances in knowledge: Spacer gel is used in prostate radiotherapy to increase distance between the prostate and the rectum, thus reducing the rectal doses. During the treatment course, gel resorption exists which affects the rectal doses. The usefulness of adaptive planning to compensate this resorption effect has not been studied before. PMID:26370300

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

PubMed

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.

A 16-channel combined loop-dipole transceiver array for 7 Tesla body MRI.

PubMed

Ertürk, M Arcan; Raaijmakers, Alexander J E; Adriany, Gregor; Uğurbil, Kâmil; Metzger, Gregory J

2017-02-01

To develop a 16-channel transceive body imaging array at 7.0 T with improved transmit, receive, and specific absorption rate (SAR) performance by combining both loop and dipole elements and using their respective and complementary near and far field characteristics. A 16-channel radiofrequency (RF) coil array consisting of eight loop-dipole blocks (16LD) was designed and constructed. Transmit and receive performance was quantitatively investigated in phantom and human model simulations, and experiments on five healthy volunteers inside the prostate. Comparisons were made with 16-channel microstrip line (16ML) and 10-channel fractionated dipole antenna (10DA) arrays. The 16LD was used to acquire anatomic and functional images of the prostate, kidneys, and heart. The 16LD provided > 14% improvements in the signal-to-noise ratio (SNR), peak B1+, B1+ transmit, and SAR efficiencies over the 16ML and 10DA in simulations inside the prostate. Experimentally, the 16LD had > 20% higher SNR and B1+ transmit efficiency compared with other arrays, and achieved up to 51.8% higher peak B1+ compared with 10DA. Combining loop and dipole elements provided a body imaging array with high channel count and density while limiting inter-element coupling. The 16LD improved both near and far-field performance compared with existing 7.0T body arrays and provided high-quality MRI of the prostate kidneys and heart. Magn Reson Med 77:884-894, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Schedule for CT image guidance in treating prostate cancer with helical tomotherapy

PubMed Central

Beldjoudi, G; Yartsev, S; Bauman, G; Battista, J; Van Dyk, J

2010-01-01

The aim of this study was to determine the effect of reducing the number of image guidance sessions and patient-specific target margins on the dose distribution in the treatment of prostate cancer with helical tomotherapy. 20 patients with prostate cancer who were treated with helical tomotherapy using daily megavoltage CT (MVCT) imaging before treatment served as the study population. The average geometric shifts applied for set-up corrections, as a result of co-registration of MVCT and planning kilovoltage CT studies over an increasing number of image guidance sessions, were determined. Simulation of the consequences of various imaging scenarios on the dose distribution was performed for two patients with different patterns of interfraction changes in anatomy. Our analysis of the daily set-up correction shifts for 20 prostate cancer patients suggests that the use of four fractions would result in a population average shift that was within 1 mm of the average obtained from the data accumulated over all daily MVCT sessions. Simulation of a scenario in which imaging sessions are performed at a reduced frequency and the planning target volume margin is adapted provided significantly better sparing of organs at risk, with acceptable reproducibility of dose delivery to the clinical target volume. Our results indicate that four MVCT sessions on helical tomotherapy are sufficient to provide information for the creation of personalised target margins and the establishment of the new reference position that accounts for the systematic error. This simplified approach reduces overall treatment session time and decreases the imaging dose to the patient. PMID:19505966

Nanoparticle-mediated siRNA delivery assessed in a 3D co-culture model simulating prostate cancer bone metastasis.

PubMed

Fitzgerald, Kathleen A; Guo, Jianfeng; Raftery, Rosanne M; Castaño, Irene Mencía; Curtin, Caroline M; Gooding, Matt; Darcy, Raphael; O' Brien, Fergal J; O' Driscoll, Caitriona M

2016-09-25

siRNA has emerged as a potential therapeutic for the treatment of prostate cancer but effective delivery remains a major barrier to its clinical application. This study aimed to develop and characterise a 3D in vitro co-culture model to simulate prostate cancer bone metastasis and to assess the ability of the model to investigate nanoparticle-mediated siRNA delivery and gene knockdown. PC3 or LNCaP prostate cancer cells were co-cultured with hFOB 1.19 osteoblast cells in 2D on plastic tissue culture plates and in 3D on collagen scaffolds mimicking the bone microenvironment. To characterise the co-culture model, cell proliferation, enzyme secretion and the utility of two different gene delivery vectors to mediate siRNA uptake and gene knockdown were assessed. Cell proliferation was reduced by∼50% by day 7 in the co-culture system relative to monoculture (PC3 and LNCaP co-cultures, in 2D and 3D) and an enhanced level of MMP9 (a marker of bone metastasis) was secreted into the media (1.2-4-fold increase depending on the co-culture system). A cationic cyclodextrin gene delivery vector proved significantly less toxic in the co-culture system relative to the commercially available vector Lipofectamine 2000(®). In addition, knockdown of both the GAPDH gene (minimum 15%) and RelA subunit of the NF-κB transcription factor (minimum 20%) was achieved in 2D and 3D cell co-cultures. Results indicate that the prostate cancer-osteoblast in vitro co-culture model was more physiologically relevant vs the monoculture. This model has the potential to help improve the design and efficacy of gene delivery formulations, to more accurately predict in vivo performance and, therefore, to reduce the risk of product failure in late-stage clinical development. Copyright © 2016 Elsevier B.V. All rights reserved.

Dosimetric evaluation of three adaptive strategies for prostate cancer treatment including pelvic lymph nodes irradiation.

PubMed

Cantin, Audrey; Gingras, Luc; Lachance, Bernard; Foster, William; Goudreault, Julie; Archambault, Louis

2015-12-01

The movements of the prostate relative to the pelvic lymph nodes during intensity-modulated radiation therapy treatment can limit margin reduction and affect the protection of the organs at risk (OAR). In this study, the authors performed an analysis of three adaptive treatment strategies that combine information from both bony and gold marker registrations. The robustness of those treatments against the interfraction prostate movements was evaluated. A retrospective study was conducted on five prostate cancer patients with 7-13 daily cone-beam CTs (CBCTs). The clinical target volumes (CTVs) consisting of pelvic lymph nodes, prostate, and seminal vesicles as well as the OARs were delineated on each CBCT and the initial CT. Three adaptive strategies were analyzed. Two of these methods relied on a two-step patient positioning at each fraction. First step: a bony registration was used to deliver the nodal CTV prescription. Second step: a gold marker registration was then used either to (1) complete the dose delivered to the prostate (complement); (2) or give almost the entire prescription to the prostate with a weak dose gradient between the targets to compensate for possible motions (gradient). The third method (COR) used a pool of precalculated plans based on images acquired at previous treatment fractions. At each new fraction, a plan is selected from that pool based on the daily position of prostate center-of-mass. The dosimetric comparison was conducted and results are presented with and without the systematic shift in the prostate position on the CT planning. The adaptive strategies were compared to the current clinical standard where all fractions are treated with the initial nonadaptive plan. The minimum daily prostate D95% is improved by 2%, 9%, and 6% for the complement, the gradient, and the COR approaches, respectively, compared to the nonadaptive method. The average nodal CTV D95% remains constant across the strategies, except for the gradient approach where a reduction of 7% is observed. However, a correction of the systematic shift reduced the problem, and the adaptive strategies remain robust against the prostate movement across the fraction. The bladder V55Gy is reduced by 35% on average for the adaptive strategies. Because they offer increased CTV coverage and OAR sparing, adaptive methods may be suitable candidates for simple and efficient adaptive treatment strategies for prostate cancer. Margin reduction and systematic error correction in the prostate position improve the protection of the OAR and the dose coverage. A cumulative dose to simulate a complete treatment would show real effects and allow a better comparison between each method.

Quality-of-life effects of prostate-specific antigen screening

PubMed Central

Heijnsdijk, EAM; Wever, EM; Auvinen, A; Hugosson, J; Ciatto, S; Nelen, V; Kwiatkowski, M; Villers, A; Páez, A; Moss, SM; Zappa, M; Tammela, TLJ; Mäkinen, T; Carlsson, S; Korfage, IJ; Essink-Bot, ML; Otto, SJ; Draisma, G; Bangma, CH; Roobol, MJ; Schröder, FH; de Koning, HJ

2016-01-01

Background The European Randomized Study of Screening for Prostate Cancer (ERSPC) reported a 29% prostate cancer mortality reduction among screened men after 11 years. However, it is uncertain to what extent harms from overdiagnosis and treatment on quality of life counterbalance this benefit. Methods Based on ERSPC follow-up data, we used micro-simulation modeling (MISCAN) to predict the number of prostate cancers, treatments, deaths and quality-adjusted life-years (QALYs) gained following the introduction of screening. Various screening strategies, efficacies, and quality of life assumptions were modeled. Results Per 1,000 men of all ages followed for their entire lifespan we predicted for annual screening from age 55–69 years: 9 fewer deaths due to prostate cancer (28% reduction), 14 fewer men receiving palliative therapy (35% reduction), and 73 life-years gained (average 8.4 years per prostate cancer death avoided). QALYs gained were 56 (range: −21, 97), a reduction of 23% from unadjusted life-years gained. The number needed to screen (NNS) was 98 and number needed to detect (NND) 5. Also inviting men aged 70–74 resulted in more life-years (82) but similar QALYs (56). Conclusions Although NNS and NND are more favorable than previously calculated, the benefit of PSA screening is diminished by loss of QALYs, that is dependent primarily on post-diagnosis long-term effects. Longer follow-up data from both the ERSPC and quality of life are essential before making universal recommendations regarding screening. PMID:22894572

14 CFR 142.3 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... accordance with subpart C of this part. Line-Operational Simulation means simulation conducted using... operations. Line operational simulation simulations are conducted for training and evaluation purposes and include random, abnormal, and emergency occurrences. Line operational simulation specifically includes...

Investigation of power and frequency for 3D conformal MRI-controlled transurethral ultrasound therapy with a dual frequency multi-element transducer.

PubMed

N'djin, William Apoutou; Burtnyk, Mathieu; Bronskill, Michael; Chopra, Rajiv

2012-01-01

Transurethral ultrasound therapy uses real-time magnetic resonance (MR) temperature feedback to enable the 3D control of thermal therapy accurately in a region within the prostate. Previous canine studies showed the feasibility of this method in vivo. The aim of this study was to reduce the procedure time, while maintaining targeting accuracy, by investigating new combinations of treatment parameters. Simulations and validation experiments in gel phantoms were used, with a collection of nine 3D realistic target prostate boundaries obtained from previous preclinical studies, where multi-slice MR images were acquired with the transurethral device in place. Acoustic power and rotation rate were varied based on temperature feedback at the prostate boundary. Maximum acoustic power and rotation rate were optimised interdependently, as a function of prostate radius and transducer operating frequency. The concept of dual frequency transducers was studied, using the fundamental frequency or the third harmonic component depending on the prostate radius. Numerical modelling enabled assessment of the effects of several acoustic parameters on treatment outcomes. The range of treatable prostate radii extended with increasing power, and tended to narrow with decreasing frequency. Reducing the frequency from 8 MHz to 4 MHz or increasing the surface acoustic power from 10 to 20 W/cm(2) led to treatment times shorter by up to 50% under appropriate conditions. A dual frequency configuration of 4/12 MHz with 20 W/cm(2) ultrasound intensity exposure can treat entire prostates up to 40 cm(3) in volume within 30 min. The interdependence between power and frequency may, however, require integrating multi-parametric functions in the controller for future optimisations.

Offline multiple adaptive planning strategy for concurrent irradiation of the prostate and pelvic lymph nodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qi, Peng; Xia, Ping, E-mail: xiap@ccf.org; Pouliot, Jean

2014-02-15

Purpose: Concurrent irradiation of the prostate and pelvic lymph nodes (PLNs) can be challenging due to the independent motion of the two target volumes. To address this challenge, the authors have proposed a strategy referred to as Multiple Adaptive Planning (MAP). To minimize the number of MAP plans, the authors’ previous work only considered the prostate motion in one major direction. After analyzing the pattern of the prostate motion, the authors investigated a practical number of intensity-modulated radiotherapy (IMRT) plans needed to accommodate the prostate motion in two major directions simultaneously. Methods: Six patients, who received concurrent irradiation of themore » prostate and PLNs, were selected for this study. Nine MAP-IMRT plans were created for each patient with nine prostate contours that represented the prostate at nine locations with respect to the PLNs, including the original prostate contour and eight contours shifted either 5 mm in a single anterior-posterior (A-P), or superior-inferior (S-I) direction, or 5 mm in both A-P and S-I directions simultaneously. From archived megavoltage cone beam CT (MV-CBCT) and a dual imaging registration, 17 MV-CBCTs from 33 available MV-CBCT from these patients showed large prostate displacements (>3 mm in any direction) with respect to the pelvic bones. For each of these 17 fractions, one of nine MAP-IMRT plans was retrospectively selected and applied to the MV-CBCT for dose calculation. For comparison, a simulated isocenter-shifting plan and a reoptimized plan were also created for each of these 17 fractions. The doses to 95% (D95) of the prostate and PLNs, and the doses to 5% (D5) of the rectum and bladder were calculated and analyzed. Results: For the prostate, D95 > 97% of the prescription dose was observed in 16, 16, and 17 of 17 fractions for the MAP, isocenter-shifted, and reoptimized plans, respectively. For PLNs, D95 > 97% of the prescription doses was observed in 10, 3, and 17 of 17 fractions for the three types of verification plans, respectively. The D5 (mean ± SD) of the rectum was 45.78 ± 5.75, 45.44 ± 4.64, and 44.64 ± 2.71 Gy, and the D5 (mean ± SD) of the bladder was 45.18 ± 2.70, 46.91 ± 3.04, and 45.67 ± 3.61 Gy for three types of verification plans, respectively. Conclusions: The MAP strategy with nine IMRT plans to accommodate the prostate motions in two major directions achieved good dose coverage to the prostate and PLNs. The MAP approach can be immediately used in clinical practice without requiring extra hardware and software.« less

14 CFR 142.3 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... instruction in accordance with subpart C of this part. Line-Operational Simulation means simulation conducted..., and ground operations. Line operational simulation simulations are conducted for training and evaluation purposes and include random, abnormal, and emergency occurrences. Line operational simulation...

14 CFR 142.3 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... instruction in accordance with subpart C of this part. Line-Operational Simulation means simulation conducted..., and ground operations. Line operational simulation simulations are conducted for training and evaluation purposes and include random, abnormal, and emergency occurrences. Line operational simulation...

14 CFR 142.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... instruction in accordance with subpart C of this part. Line-Operational Simulation means simulation conducted..., and ground operations. Line operational simulation simulations are conducted for training and evaluation purposes and include random, abnormal, and emergency occurrences. Line operational simulation...

Computerized transrectal ultrasound (C-TRUS) of the prostate: detection of cancer in patients with multiple negative systematic random biopsies.

PubMed

Loch, Tillmann

2007-08-01

This study was designed to compare the diagnostic yield of computerized transrectal ultrasound (C-TRUS) guided biopsies in the detection of prostate cancer in a group of men with a history of multiple systematic random biopsies with no prior evidence of prostate cancer. The question was asked: Can we detect cancer by C-TRUS that has been overlooked by multiple systematic biopsies? The entrance criteria for this study were prior negative systematic random biopsies regardless of number of biopsy sessions or number of individual biopsy cores. Serial static TRUS images were evaluated by C-TRUS, which assessed signal information independent of visual gray scale. Five C-TRUS algorithms were utilized to evaluate the information of the ultrasound signal. Interpretation of the results were documented and the most suspicious regions marked by C-TRUS were biopsied by guiding the needle to the marked location. Five hundred and forty men were biopsied because of an elevated PSA or abnormal digital rectal exam. 132 had a history of prior negative systematic random biopsies (1-7 sessions, median: 2 and between 6 and 72 individual prostate biopsies, median: 12 cores). Additionally, a diagnostic TUR-P of the prostate with benign result was performed in four patients. The PSA ranged from 3.1-36 ng/ml with a median of 9.01 ng/ml. The prostate volume ranged from 6-203 ml with a median of 42 ml. Of the 132 patients with prior negative systematic random biopsies, cancer was found in 66 (50%) by C-TRUS targeted biopsies. In this group the median number of negative biopsy sessions was two and a median of 12 biopsy cores were performed. From literature we would expect a cancer detection rate in this group with systematic biopsies of approximately 7%. We only found five carcinomas with a Gleason Score (GS) of 5, 25 with GS 6, 22 with GS 7, 8 with GS 8 and even 7 with GS 9. The results of this prospective clinical trail indicates that the additional use of the C-TRUS identifies clinical significant cancerous lesions that could not been visualized or detected by systematic random biopsies in a very high percentage. In addition, the results of the study support the efforts to search for strategies that utilize expertise and refinement of imaging modalities rather than elevating the number of random biopsies (f.e. 141 cores in one session) in the detection of prostate cancer.

Evaluation of Genomic Instability in the Abnormal Prostate

DTIC Science & Technology

2008-12-01

Research 63, 4781-5. (24) Mehrotra, J., Varde, S., Wang, H., Chiu, H., Vargo, J., Gray , K., Nagle, R.B., Neri, J.R., Mazumder, A. (2007) Quantitative...examined. B-actin was used as the internal control (not shown). Figure 6 Figure 6. Telomere Content of samples by tissue source. The gray ...TTC GGG GTG TAG CG-6-TAMSp-3’ RassF1A Forward 5’-GCG TTG AAG TCG GGG TTC-3’ RassF1A Reverse 5’-CCC GTA CTT CGC TAA CTT TAA ACG-3’ RassF1A Probe 5

Prevalence of Prostate Cancer Clinical States and Mortality in the United States: Estimates Using a Dynamic Progression Model

PubMed Central

Scher, Howard I.; Solo, Kirk; Valant, Jason; Todd, Mary B.; Mehra, Maneesha

2015-01-01

Objective To identify patient populations most in need of treatment across the prostate cancer disease continuum, we developed a novel dynamic transition model based on risk of disease progression and mortality. Design and Outcome Measurements We modeled the flow of patient populations through eight prostate cancer clinical states (PCCS) that are characterized by the status of the primary tumor, presence of metastases, prior and current treatment, and testosterone levels. Simulations used published US incidence rates for each year from 1990. Progression and mortality rates were derived from published clinical trials, meta-analyses, and observational studies. Model outputs included the incidence, prevalence, and mortality for each PCCS. The impact of novel treatments was modeled in three distinct scenarios: metastatic castration-resistant prostate cancer (mCRPC), non-metastatic CRPC (nmCRPC), or both. Results and Limitations The model estimated the prevalence of prostate cancer as 2,219,280 in the US in 2009 and 3,072,480 in 2020, and incidence of mCRPC as 36,100 and 42,970, respectively. All-cause mortality in prostate cancer was estimated at 168,290 in 2009 and 219,360 in 2020, with 20.5% and 19.5% of these deaths, respectively, occurring in men with mCRPC. The majority (86%) of incidence flow into mCRPC states was from the nmCRPC clinical state. In the scenario with novel interventions for nmCRPC states, the progression to mCRPC is reduced, thus decreasing mCRPC incidence by 12% in 2020, with a sustained decline in mCRPC mortality. A limitation of the model is that it does not estimate prostate cancer—specific mortality. Conclusion The model informs clinical trial design for prostate cancer by quantifying outcomes in PCCS, and demonstrates the impact of an effective therapy applied in an earlier clinical state of nmCRPC on the incidence of mCRPC morbidity and subsequent mortality. PMID:26460686

The Use of Fluoroproline in MUC1 Antigen Enables Efficient Detection of Antibodies in Patients with Prostate Cancer.

PubMed

Somovilla, Víctor J; Bermejo, Iris A; Albuquerque, Inês S; Martínez-Sáez, Nuria; Castro-López, Jorge; García-Martín, Fayna; Compañón, Ismael; Hinou, Hiroshi; Nishimura, Shin-Ichiro; Jiménez-Barbero, Jesús; Asensio, Juan L; Avenoza, Alberto; Busto, Jesús H; Hurtado-Guerrero, Ramón; Peregrina, Jesús M; Bernardes, Gonçalo J L; Corzana, Francisco

2017-12-20

A structure-based design of a new generation of tumor-associated glycopeptides with improved affinity against two anti-MUC1 antibodies is described. These unique antigens feature a fluorinated proline residue, such as a (4S)-4-fluoro-l-proline or 4,4-difluoro-l-proline, at the most immunogenic domain. Binding assays using biolayer interferometry reveal 3-fold to 10-fold affinity improvement with respect to the natural (glyco)peptides. According to X-ray crystallography and MD simulations, the fluorinated residues stabilize the antigen-antibody complex by enhancing key CH/π interactions. Interestingly, a notable improvement in detection of cancer-associated anti-MUC1 antibodies from serum of patients with prostate cancer is achieved with the non-natural antigens, which proves that these derivatives can be considered better diagnostic tools than the natural antigen for prostate cancer.

TOPEM: A PET-TOF endorectal probe, compatible with MRI for diagnosis and follow up of prostate cancer

NASA Astrophysics Data System (ADS)

Garibaldi, F.; Capuani, S.; Colilli, S.; Cosentino, L.; Cusanno, F.; De Leo, R.; Finocchiaro, P.; Foresta, M.; Giove, F.; Giuliani, F.; Gricia, M.; Loddo, F.; Lucentini, M.; Maraviglia, B.; Meddi, F.; Monno, E.; Musico, P.; Pappalardo, A.; Perrino, R.; Ranieri, A.; Rivetti, A.; Santavenere, F.; Tamma, C.

2013-02-01

Prostate cancer is the most common disease in men and the second leading cause of cancer death. Generic large instruments for diagnosis have sensitivity, spatial resolution, and contrast inferior with respect to dedicated prostate imagers. Multimodality imaging can play a significant role merging anatomical and functional details coming from simultaneous PET and MRI. The TOPEM project has the goal of designing, building, and testing an endorectal PET-TOF MRI probe. The performance is dominated by the detector close to the source. Results from simulation show spatial resolution of ∼1.5 mm for source distances up to 80 mm. The efficiency is significantly improved with respect to the external PET. Mini-detectors have been built and tested. We obtained, for the first time, to our best knowledge, timing resolution of <400 ps and at the same time Depth Of Interaction (DOI) resolution of 1 mm or less.

A nonlinear competitive model of the prostate tumor growth under intermittent androgen suppression.

PubMed

Yang, Jing; Zhao, Tong-Jun; Yuan, Chang-Qing; Xie, Jing-Hui; Hao, Fang-Fang

2016-09-07

Hormone suppression has been the primary modality of treatment for prostate cancer. However long-term androgen deprivation may induce androgen-independent (AI) recurrence. Intermittent androgen suppression (IAS) is a potential way to delay or avoid the AI relapse. Mathematical models of tumor growth and treatment are simple while they are capable of capturing the essence of complicated interactions. Game theory models have analyzed that tumor cells can enhance their fitness by adopting genetically determined survival strategies. In this paper, we consider the survival strategies as the competitive advantage of tumor cells and propose a new model to mimic the prostate tumor growth in IAS therapy. Then we investigate the competition effect in tumor development by numerical simulations. The results indicate that successfully IAS-controlled states can be achieved even though the net growth rate of AI cells is positive for any androgen level. There is crucial difference between the previous models and the new one in the phase diagram of successful and unsuccessful tumor control by IAS administration, which means that the suggestions from the models for medication can be different. Furthermore we introduce quadratic logistic terms to the competition model to simulate the tumor growth in the environment with a finite carrying capacity considering the nutrients or inhibitors. The simulations show that the tumor growth can reach an equilibrium state or an oscillatory state with the net growth rate of AI cells being androgen independent. Our results suggest that the competition and the restraint of a limited environment can enhance the possibility of relapse prevention. Copyright © 2016 Elsevier Ltd. All rights reserved.

Irreversible electroporation: Just another form of thermal therapy?

PubMed Central

van Gemert, Martin J C; Wagstaff, Peter G K; de Bruin, Daniel M; van Leeuwen, Ton G; van der Wal, Allard C; Heger, Michal; van der Geld, Cees W M

2015-01-01

Background Irreversible electroporation (IRE) is (virtually) always called non-thermal despite many reports showing that significant Joule heating occurs. Our first aim is to validate with mathematical simulations that IRE as currently practiced has a non-negligible thermal response. Our second aim is to present a method that allows simple temperature estimation to aid IRE treatment planning. Methods We derived an approximate analytical solution of the bio-heat equation for multiple 2-needle IRE pulses in an electrically conducting medium, with and without a blood vessel, and incorporated published observations that an electric pulse increases the medium's electric conductance. Results IRE simulation in prostate-resembling tissue shows thermal lesions with 67–92°C temperatures, which match the positions of the coagulative necrotic lesions seen in an experimental study. Simulation of IRE around a blood vessel when blood flow removes the heated blood between pulses confirms clinical observations that the perivascular tissue is thermally injured without affecting vascular patency. Conclusions The demonstration that significant Joule heating surrounds current multiple-pulsed IRE practice may contribute to future in-depth discussions on this thermal issue. This is an important subject because it has long been under-exposed in literature. Its awareness pleads for preventing IRE from calling “non-thermal” in future publications, in order to provide IRE-users with the most accurate information possible. The prospect of thermal treatment planning as outlined in this paper likely aids to the important further successful dissemination of IRE in interventional medicine. Prostate 75:332–335, 2015. © 2014 The Authors. The Prostate Published by Wiley Periodicals, Inc. PMID:25327875

Assessment of Prospectively Assigned Likert Scores for Targeted Magnetic Resonance Imaging-Transrectal Ultrasound Fusion Biopsies in Patients with Suspected Prostate Cancer.

PubMed

Costa, Daniel N; Lotan, Yair; Rofsky, Neil M; Roehrborn, Claus; Liu, Alexander; Hornberger, Brad; Xi, Yin; Francis, Franto; Pedrosa, Ivan

2016-01-01

We assess the performance of prospectively assigned magnetic resonance imaging based Likert scale scores for the detection of clinically significant prostate cancer, and analyze the pre-biopsy imaging variables associated with increased cancer detection using targeted magnetic resonance imaging-transrectal ultrasound fusion biopsy. In this retrospective review of prospectively generated data including men with abnormal multiparametric prostate magnetic resonance imaging (at least 1 Likert score 3 or greater lesion) who underwent subsequent targeted magnetic resonance imaging-transrectal ultrasound fusion biopsy, we determined the association between different imaging variables (Likert score, lesion size, lesion location, prostate volume, radiologist experience) and targeted biopsy positivity rate. We also compared the detection of clinically significant cancer according to Likert scale scores. Tumors with high volume (50% or more of any core) Gleason score 3+4 or any tumor with greater Gleason score were considered clinically significant. Each lesion served as the elementary unit for analysis. We used logistic regression for univariate and multivariate (stepwise selection) analysis to assess for an association between targeted biopsy positivity rate and each tested variable. The relationship between Likert scale and Gleason score was evaluated using the Spearman correlation coefficient. A total of 161 men with 244 lesions met the study eligibility criteria. Targeted biopsies diagnosed cancer in 41% (66 of 161) of the men and 41% (99 of 244) of the lesions. The Likert score was the strongest predictor of targeted biopsy positivity (OR 3.7, p <0.0001). Other imaging findings associated with a higher targeted biopsy positivity rate included smaller prostate volume (OR 0.7, p <0.01), larger lesion size (OR 2.2, p <0.001) and anterior location (OR 2.0, p=0.01). On multiple logistic regression analysis Likert score, lesion size and prostate volume were significant predictors of targeted biopsy positivity. Higher Likert scores were also associated with increased detection of clinically significant tumors (p <0.0001). The Likert scale score used to convey the degree of suspicion on multiparametric magnetic resonance imaging is the strongest predictor of targeted biopsy positivity and of the presence of clinically significant tumor. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A novel urinary long non-coding RNA transcript improves diagnostic accuracy in patients undergoing prostate biopsy.

PubMed

Zhang, Wei; Ren, Shan-Cheng; Shi, Xiao-Lei; Liu, Ya-Wei; Zhu, Ya-Sheng; Jing, Tai-Le; Wang, Fu-Bo; Chen, Rui; Xu, Chuan-Liang; Wang, Hui-Qing; Wang, Hai-Feng; Wang, Yan; Liu, Bing; Li, Yao-Ming; Fang, Zi-Yu; Guo, Fei; Lu, Xin; Shen, Dan; Gao, Xu; Hou, Jian-Guo; Sun, Ying-Hao

2015-05-01

Long non-coding RNA (LncRNA) PCA3 has been a well-established urine biomarker for the detection of prostate cancer (PCa). Our previous study showed a novel LncRNA FR0348383 is up-regulated in over 70% of PCa compared with matched benign tissues. The aim of this study was to evaluate the diagnostic value of urinary FR0348383 for men undergoing prostate biopsy due to elevated PSA (PSA > 4.0 ng/ml) and/or abnormal digital rectal examination (DRE). Post-DRE first-catch urine specimens prior to prostate biopsies were prospectively collected. After the whole transcriptome amplification, quantitative real time polymerase chain reaction was applied to quantify urine FR0348383 and PSA levels. The FR0348383 score was calculated as the ratio of PSA and FR0348383 mRNA (PSA mRNA/FR0348383 mRNA × 1000). The diagnostic value of FR0348383 score was evaluated by logistic regression and decision curve analysis. 213 cases with urine samples containing sufficient mRNA were included, 94 cases had serum PSA level 4.0-10.0 ng/ml. PCa was identified in 72 cases. An increasing FR0348383 score was correlated with an increasing probability of a positive biopsy (P < 0.001). Multivariable logistic analysis indicated FR0348383 score (P < 0.001), PSA (P = 0.004), age (P = 0.007), prostate volume (P < 0.001) were independent predictors of PCa. ROC analysis demonstrated FR0348383 score outperformed PSA, %free PSA, and PSA Density in the prediction of PCa in the subgroup of patients with grey area PSA (AUC: 0.815 vs. 0.562 vs. 0.599 vs. 0.645). When using a probability threshold of 30% in the grey zone cohort, The FR0348383 score would save 52.0% of avoidable biopsies without missing any high grade cancers. FR0348383 transcript in post-DRE urine may be a novel biomarker for detection of PCa with great diagnostic value, especially in the grey zone cohort. The application of FR0348383 score in clinical practice might avoid unnecessary prostate biopsies and increase the specificity of PCa diagnosis. © 2015 Wiley Periodicals, Inc.

A Monte Carlo study of I-125 prostate brachytherapy with gold nanoparticles: dose enhancement with simultaneous rectal dose sparing via radiation shielding.

PubMed

Brivio, D; Nguyen, P L; Sajo, E; Ngwa, W; Zygmanski, P

2017-03-07

We investigate via Monte Carlo simulations a new 125 I brachytherapy treatment technique for high-risk prostate cancer patients via injection of Au nanoparticle (AuNP) directly into the prostate. The purpose of using the nanoparticles is to increase the therapeutic index via two synergistic effects: enhanced energy deposition within the prostate and simultaneous shielding of organs at risk from radiation escaping from the prostate. Both uniform and non-uniform concentrations of AuNP are studied. The latter are modeled considering the possibility of AuNP diffusion after the injection using brachy needles. We study two extreme cases of coaxial AuNP concentrations: centered on brachy needles and centered half-way between them. Assuming uniform distribution of 30 mg g -1 of AuNP within the prostate, we obtain a dose enhancement larger than a factor of 2 to the prostate. Non-uniform concentration of AuNP ranging from 10 mg g -1 and 66 mg g -1 were studied. The higher the concentration in a given region of the prostate the greater is the enhancement therein. We obtain the highest dose enhancement when the brachytherapy needles are coincident with AuNP injection needles but, at the same time, the regions in the tail are colder (average dose ratio of 0.7). The best enhancement uniformity is obtained with the seeds in the tail of the AuNP distribution. In both uniform and non-uniform cases the urethra and rectum receive less than 1/3 dose compared to an analog treatment without AuNP. Remarkably, employing AuNP not only significantly increases dose to the target but also decreases dose to the neighboring rectum and even urethra, which is embedded within the prostate. These are mutually interdependent effects as more enhancement leads to more shielding and vice-versa. Caution must be paid since cold spot or hot spots may be created if the AuNP concentration versus seed position is not properly distributed respect to the seed locations.

A Monte Carlo study of I-125 prostate brachytherapy with gold nanoparticles: dose enhancement with simultaneous rectal dose sparing via radiation shielding

NASA Astrophysics Data System (ADS)

Brivio, D.; Nguyen, P. L.; Sajo, E.; Ngwa, W.; Zygmanski, P.

2017-03-01

We investigate via Monte Carlo simulations a new 125I brachytherapy treatment technique for high-risk prostate cancer patients via injection of Au nanoparticle (AuNP) directly into the prostate. The purpose of using the nanoparticles is to increase the therapeutic index via two synergistic effects: enhanced energy deposition within the prostate and simultaneous shielding of organs at risk from radiation escaping from the prostate. Both uniform and non-uniform concentrations of AuNP are studied. The latter are modeled considering the possibility of AuNP diffusion after the injection using brachy needles. We study two extreme cases of coaxial AuNP concentrations: centered on brachy needles and centered half-way between them. Assuming uniform distribution of 30 mg g-1 of AuNP within the prostate, we obtain a dose enhancement larger than a factor of 2 to the prostate. Non-uniform concentration of AuNP ranging from 10 mg g-1 and 66 mg g-1 were studied. The higher the concentration in a given region of the prostate the greater is the enhancement therein. We obtain the highest dose enhancement when the brachytherapy needles are coincident with AuNP injection needles but, at the same time, the regions in the tail are colder (average dose ratio of 0.7). The best enhancement uniformity is obtained with the seeds in the tail of the AuNP distribution. In both uniform and non-uniform cases the urethra and rectum receive less than 1/3 dose compared to an analog treatment without AuNP. Remarkably, employing AuNP not only significantly increases dose to the target but also decreases dose to the neighboring rectum and even urethra, which is embedded within the prostate. These are mutually interdependent effects as more enhancement leads to more shielding and vice-versa. Caution must be paid since cold spot or hot spots may be created if the AuNP concentration versus seed position is not properly distributed respect to the seed locations.

SU-G-BRA-12: Development of An Intra-Fractional Motion Tracking and Dose Reconstruction System for Adaptive Stereotactic Body Radiation Therapy in High-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rezaeian, N Hassan; Chi, Y; Tian, Z

Purpose: A clinical trial on stereotactic body radiation therapy (SBRT) for high-risk prostate cancer is undergoing at our institution. In addition to escalating dose to the prostate, we have increased dose to intra-prostatic lesions. Intra-fractional prostate motion deteriorates well planned radiation dose, especially for the small intra-prostatic lesions. To solve this problem, we have developed a motion tracking and 4D dose-reconstruction system to facilitate adaptive re-planning. Methods: Patients in the clinical trial were treated with VMAT using four arcs and 10 FFF beam. KV triggered x-ray projections were taken every 3 sec during delivery to acquire 2D projections of 3Dmore » anatomy at the direction orthogonal to the therapeutic beam. Each patient had three implanted prostate markers. Our developed system first determined 2D projection locations of these markers and then 3D prostate translation and rotation via 2D/3D registration of the markers. Using delivery log files, our GPU-based Monte Carlo tool (goMC) reconstructed dose corresponding to each triggered image. The calculated 4D dose distributions were further aggregated to yield the delivered dose. Results: We first tested each module in our system. MC dose engine were commissioned to our treatment planning system with dose difference of <0.5%. For motion tracking, 1789 kV projections from 7 patients were acquired. The 2D marker location error was <1 mm. For 3D motion tracking, root mean square (RMS) errors along LR, AP, and CC directions were 0.26mm, 0.36mm, and 0.01mm respectively in simulation studies and 1.99mm, 1.37mm, and 0.22mm in phantom studies. We also tested the entire system workflow. Our system was able to reconstruct delivered dose. Conclusion: We have developed a functional intra-fractional motion tracking and 4D dose re-construction system to support our clinical trial on adaptive high-risk prostate cancer SBRT. Comprehensive evaluations have shown the capability and accuracy of our system.« less

Poster — Thur Eve — 13: Inter-Fraction Target Movement in Image-Guided Radiation Therapy of Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cui, Congwu; Zeng, Grace G.; Department of Radiation Oncology, University of Toronto, Toronto, ON

2014-08-15

We investigated the setup variations over the treatment courses of 113 patients with intact prostate treated with 78Gy/39fx. Institutional standard bladder and bowel preparation and image guidance protocols were used in CT simulation and treatment. The RapidArc treatment plans were optimized in Varian Eclipse treatment planning system and delivered on Varian 2100X Clinacs equipped with On-Board Imager to localize the target before beam-on. The setup variations were calculated in terms of mean and standard deviation of couch shifts. No correlation was observed between the mean shift and standard deviation over the treatment course and patient age, initial prostate volume andmore » rectum size. The mean shifts in the first and last 5 fractions are highly correlated (P < 10{sup −10}) while the correlation of the standard deviations cannot be determined. The Mann-Kendall tests indicate trends of the mean daily Ant-Post and Sup-Inf shifts of the group. The target is inferior by ∼1mm to the planned position when the treatment starts and moves superiorly, approaching the planned position at 10th fraction, and then gradually moves back inferiorly by ∼1mm in the remain fractions. In the Ant-Post direction, the prostate gradually moves posteriorly during the treatment course from a mean shift of ∼2.5mm in the first fraction to ∼1mm in the last fraction. It may be related to a systematic rectum size change in the progress of treatment. The biased mean shifts in Ant-Post and Sup-Inf direction of most patients suggest systematically larger rectum and smaller bladder during the treatment than at CT simulation.« less

Development of an adjoint sensitivity field-based treatment-planning technique for the use of newly designed directional LDR sources in brachytherapy.

PubMed

Chaswal, V; Thomadsen, B R; Henderson, D L

2012-02-21

The development and application of an automated 3D greedy heuristic (GH) optimization algorithm utilizing the adjoint sensitivity fields for treatment planning to assess the advantage of directional interstitial prostate brachytherapy is presented. Directional and isotropic dose kernels generated using Monte Carlo simulations based on Best Industries model 2301 I-125 source are utilized for treatment planning. The newly developed GH algorithm is employed for optimization of the treatment plans for seven interstitial prostate brachytherapy cases using mixed sources (directional brachytherapy) and using only isotropic sources (conventional brachytherapy). All treatment plans resulted in V100 > 98% and D90 > 45 Gy for the target prostate region. For the urethra region, the D10(Ur), D90(Ur) and V150(Ur) and for the rectum region the V100cc, D2cc, D90(Re) and V90(Re) all are reduced significantly when mixed sources brachytherapy is used employing directional sources. The simulations demonstrated that the use of directional sources in the low dose-rate (LDR) brachytherapy of the prostate clearly benefits in sparing the urethra and the rectum sensitive structures from overdose. The time taken for a conventional treatment plan is less than three seconds, while the time taken for a mixed source treatment plan is less than nine seconds, as tested on an Intel Core2 Duo 2.2 GHz processor with 1GB RAM. The new 3D GH algorithm is successful in generating a feasible LDR brachytherapy treatment planning solution with an extra degree of freedom, i.e. directionality in very little time.

Development of an adjoint sensitivity field-based treatment-planning technique for the use of newly designed directional LDR sources in brachytherapy

NASA Astrophysics Data System (ADS)

Chaswal, V.; Thomadsen, B. R.; Henderson, D. L.

2012-02-01

The development and application of an automated 3D greedy heuristic (GH) optimization algorithm utilizing the adjoint sensitivity fields for treatment planning to assess the advantage of directional interstitial prostate brachytherapy is presented. Directional and isotropic dose kernels generated using Monte Carlo simulations based on Best Industries model 2301 I-125 source are utilized for treatment planning. The newly developed GH algorithm is employed for optimization of the treatment plans for seven interstitial prostate brachytherapy cases using mixed sources (directional brachytherapy) and using only isotropic sources (conventional brachytherapy). All treatment plans resulted in V100 > 98% and D90 > 45 Gy for the target prostate region. For the urethra region, the D10Ur, D90Ur and V150Ur and for the rectum region the V100cc, D2cc, D90Re and V90Re all are reduced significantly when mixed sources brachytherapy is used employing directional sources. The simulations demonstrated that the use of directional sources in the low dose-rate (LDR) brachytherapy of the prostate clearly benefits in sparing the urethra and the rectum sensitive structures from overdose. The time taken for a conventional treatment plan is less than three seconds, while the time taken for a mixed source treatment plan is less than nine seconds, as tested on an Intel Core2 Duo 2.2 GHz processor with 1GB RAM. The new 3D GH algorithm is successful in generating a feasible LDR brachytherapy treatment planning solution with an extra degree of freedom, i.e. directionality in very little time.

Robust and efficient pharmacokinetic parameter non-linear least squares estimation for dynamic contrast enhanced MRI of the prostate.

PubMed

Kargar, Soudabeh; Borisch, Eric A; Froemming, Adam T; Kawashima, Akira; Mynderse, Lance A; Stinson, Eric G; Trzasko, Joshua D; Riederer, Stephen J

2018-05-01

To describe an efficient numerical optimization technique using non-linear least squares to estimate perfusion parameters for the Tofts and extended Tofts models from dynamic contrast enhanced (DCE) MRI data and apply the technique to prostate cancer. Parameters were estimated by fitting the two Tofts-based perfusion models to the acquired data via non-linear least squares. We apply Variable Projection (VP) to convert the fitting problem from a multi-dimensional to a one-dimensional line search to improve computational efficiency and robustness. Using simulation and DCE-MRI studies in twenty patients with suspected prostate cancer, the VP-based solver was compared against the traditional Levenberg-Marquardt (LM) strategy for accuracy, noise amplification, robustness to converge, and computation time. The simulation demonstrated that VP and LM were both accurate in that the medians closely matched assumed values across typical signal to noise ratio (SNR) levels for both Tofts models. VP and LM showed similar noise sensitivity. Studies using the patient data showed that the VP method reliably converged and matched results from LM with approximate 3× and 2× reductions in computation time for the standard (two-parameter) and extended (three-parameter) Tofts models. While LM failed to converge in 14% of the patient data, VP converged in the ideal 100%. The VP-based method for non-linear least squares estimation of perfusion parameters for prostate MRI is equivalent in accuracy and robustness to noise, while being more reliably (100%) convergent and computationally about 3× (TM) and 2× (ETM) faster than the LM-based method. Copyright © 2017 Elsevier Inc. All rights reserved.

Dose perturbation due to the presence of a prostatic urethral stent in patients receiving pelvic radiotherapy: an in vitro study.

PubMed

Gez, E; Cederbaum, M; Yachia, D; Bar-Deroma, R; Kuten, A

1997-01-01

Temporary metallic intraprostatic stent is a new alternative treatment for patients with urinary obstructive syndrome caused by prostate cancer. Definitive radiotherapy is a treatment of choice for localized prostate cancer. This study evaluates in vitro the effect of a urethral intraprostatic metallic stent on the dose absorbed by the surrounding tissue. The study was designed to mimic the conditions under which the prostatic stent is placed in the body during pelvic irradiation. A urethral stent composed of a 50% nickel-50% titanium alloy (Uracoil-InStent) was imbedded in material mimicking normal tissue (bolus) at a simulated body depth of 10 cm. The distribution of the absorbed dose of irradiation was determined by film dosimetry using Kodak X-Omat V film. Irradiation was done in a single field at the isocenter of a 6 MV linear accelerator with a field size of 7 x 7 cm. The degree of film blackening was in direct proportion to the absorbed dose. The measurements showed an increase in dose of up to 20% immediately before the stent and a decrease of up to 18% immediately after the stent. These changes occurred within a range of 1-3 mm from both sides of the stent. In practice, irradiation in prostate cancer is given by two pairs of opposed co-axial fields; a total of four fields (Box Technique). The dose perturbations are partly cancelled in a pair of opposed beams resulting in a net variation of +/- 4%; therefore, the presence of the intraprostatic stent should not influence radiotherapy planning for prostate cancer.

Positioning accuracy and daily dose assessment for prostate cancer treatment using in-room CT image guidance at a proton therapy facility.

PubMed

Maeda, Yoshikazu; Sato, Yoshitaka; Minami, Hiroki; Yasukawa, Yutaka; Yamamoto, Kazutaka; Tamamura, Hiroyasu; Shibata, Satoshi; Bou, Sayuri; Sasaki, Makoto; Tameshige, Yuji; Kume, Kyo; Ooto, Hiroshi; Kasahara, Shigeru; Shimizu, Yasuhiro; Saga, Yusuke; Omoya, Akira; Saitou, Makoto

2018-05-01

To evaluate the effectiveness of CT image-guided proton radiotherapy for prostate cancer by analyzing the positioning uncertainty and assessing daily dose change due to anatomical variations. Patients with prostate cancer were treated by opposed lateral proton beams based on a passive scattering method using an in-room CT image-guided system. The system employs a single couch for both CT scanning and beam delivery. The patient was positioned by matching the boundary between the prostate and the rectum's anterior region identified in the CT images to the corresponding boundary in the simulator images after bone matching. We acquired orthogonal kV x-ray images after couch movement and confirmed the body position by referring to the bony structure prior to treatment. In offline analyses, we contoured the targeted anatomical structures on 375 sets of daily in-room CT images for 10 patients. The uncertainty of the image-matching procedure was evaluated using the prostate contours and actual couch corrections. We also performed dose calculations using the same set of CT images, and evaluated daily change of dose-volume histograms (DVHs) to compare the effectiveness of the treatment using prostate matching to the bone-matching procedure. The isocenter shifts by prostate matching after bone matching were 0.5 ± 1.8 and -0.8 ± 2.6 mm along the superior-inferior (SI) and anterior-posterior (AP) directions, respectively. The body movement errors (σ) after couch movement were 0.7, 0.5, and 0.3 mm along the lateral, SI and AP direction, respectively, for 30 patients. The estimated errors (σ) in the prostate matching were 1.0 and 1.3 mm, and, in conjunction with the movement errors, the total positioning uncertainty was estimated to be 1.0 and 1.4 mm along the SI and AP directions, respectively. Daily DVH analyses showed that in the prostate matching, 98.7% and 86.1% of the total 375 irradiations maintained a dose condition of V 95%  > 95% for the prostate and a dose constraint of V 77%  < 18% for the rectum, whereas 90.4% and 66.1% of the total irradiations did so when bone matching was used. The dose constraint of the rectum and dose coverage of the prostate were better maintained by prostate matching than bone matching (P < 0.001). The daily variation in the dose to the seminal vesicles (SVs) was large, and only 40% of the total irradiations maintained the initial planned values of V 95% for high-risk treatment. Nevertheless, the deviations from the original value were -4 ± 7% and -5 ± 11% in the prostate and bone matching, respectively, and a better dose coverage of the SV was achieved by the prostate matching. The correction of repositioning along the AP and SI direction from conventional bone matching in CT image-guided proton therapy was found to be effective to maintain the dose constraint of the rectum and the dose coverage of the prostate. This work indicated that prostate cancer treatment by prostate matching using CT image guidance may be effective to reduce the rectal complications and achieve better tumor control of the prostate. However, an adaptive approach is desirable to maintain better dose coverage of the SVs. © 2018 American Association of Physicists in Medicine.

A model describing diffusion in prostate cancer.

PubMed

Gilani, Nima; Malcolm, Paul; Johnson, Glyn

2017-07-01

Quantitative diffusion MRI has frequently been studied as a means of grading prostate cancer. Interpretation of results is complicated by the nature of prostate tissue, which consists of four distinct compartments: vascular, ductal lumen, epithelium, and stroma. Current diffusion measurements are an ill-defined weighted average of these compartments. In this study, prostate diffusion is analyzed in terms of a model that takes explicit account of tissue compartmentalization, exchange effects, and the non-Gaussian behavior of tissue diffusion. The model assumes that exchange between the cellular (ie, stromal plus epithelial) and the vascular and ductal compartments is slow. Ductal and cellular diffusion characteristics are estimated by Monte Carlo simulation and a two-compartment exchange model, respectively. Vascular pseudodiffusion is represented by an additional signal at b = 0. Most model parameters are obtained either from published data or by comparing model predictions with the published results from 41 studies. Model prediction error is estimated using 10-fold cross-validation. Agreement between model predictions and published results is good. The model satisfactorily explains the variability of ADC estimates found in the literature. A reliable model that predicts the diffusion behavior of benign and cancerous prostate tissue of different Gleason scores has been developed. Magn Reson Med 78:316-326, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Dosimetric effects of seed anisotropy and interseed attenuation for {sup 103}Pd and {sup 125}I prostate implants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chibani, Omar; Williamson, Jeffrey F.; Todor, Dorin

2005-08-15

A Monte Carlo study is carried out to quantify the effects of seed anisotropy and interseed attenuation for {sup 103}Pd and {sup 125}I prostate implants. Two idealized and two real prostate implants are considered. Full Monte Carlo simulation (FMCS) of implants (seeds are physically and simultaneously simulated) is compared with isotropic point-source dose-kernel superposition (PSKS) and line-source dose-kernel superposition (LSKS) methods. For clinical pre- and post-procedure implants, the dose to the different structures (prostate, rectum wall, and urethra) is calculated. The discretized volumes of these structures are reconstructed using transrectal ultrasound contours. Local dose differences (PSKS versus FMCS and LSKSmore » versus FMCS) are investigated. The dose contributions from primary versus scattered photons are calculated separately. For {sup 103}Pd, the average absolute total dose difference between FMCS and PSKS can be as high as 7.4% for the idealized model and 6.1% for the clinical preprocedure implant. Similarly, the total dose difference is lower for the case of {sup 125}I: 4.4% for the idealized model and 4.6% for a clinical post-procedure implant. Average absolute dose differences between LSKS and FMCS are less significant for both seed models: 3 to 3.6% for the idealized models and 2.9 to 3.2% for the clinical plans. Dose differences between PSKS and FMCS are due to the absence of both seed anisotropy and interseed attenuation modeling in the PSKS approach. LSKS accounts for seed anisotropy but not for the interseed effect, leading to systematically overestimated dose values in comparison with the more accurate FMCS method. For both idealized and clinical implants the dose from scattered photons represent less than 1/3 of the total dose. For all studied cases, LSKS prostate DVHs overestimate D{sub 90} by 2 to 5% because of the missing interseed attenuation effect. PSKS and LSKS predictions of V{sub 150} and V{sub 200} are overestimated by up to 9% in comparison with the FMCS results. Finally, effects of seed anisotropy and interseed attenuation must be viewed in the context of other significant sources of dose uncertainty, namely seed orientation, source misplacement, prostate morphological changes and tissue heterogeneity.« less

Dosimetric evaluation of three adaptive strategies for prostate cancer treatment including pelvic lymph nodes irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cantin, Audrey; Gingras, Luc; Archambault, Louis, E-mail: louis.archambault@phy.ulaval.ca

Purpose: The movements of the prostate relative to the pelvic lymph nodes during intensity-modulated radiation therapy treatment can limit margin reduction and affect the protection of the organs at risk (OAR). In this study, the authors performed an analysis of three adaptive treatment strategies that combine information from both bony and gold marker registrations. The robustness of those treatments against the interfraction prostate movements was evaluated. Methods: A retrospective study was conducted on five prostate cancer patients with 7–13 daily cone-beam CTs (CBCTs). The clinical target volumes (CTVs) consisting of pelvic lymph nodes, prostate, and seminal vesicles as well asmore » the OARs were delineated on each CBCT and the initial CT. Three adaptive strategies were analyzed. Two of these methods relied on a two-step patient positioning at each fraction. First step: a bony registration was used to deliver the nodal CTV prescription. Second step: a gold marker registration was then used either to (1) complete the dose delivered to the prostate (complement); (2) or give almost the entire prescription to the prostate with a weak dose gradient between the targets to compensate for possible motions (gradient). The third method (COR) used a pool of precalculated plans based on images acquired at previous treatment fractions. At each new fraction, a plan is selected from that pool based on the daily position of prostate center-of-mass. The dosimetric comparison was conducted and results are presented with and without the systematic shift in the prostate position on the CT planning. The adaptive strategies were compared to the current clinical standard where all fractions are treated with the initial nonadaptive plan. Results: The minimum daily prostate D{sub 95%} is improved by 2%, 9%, and 6% for the complement, the gradient, and the COR approaches, respectively, compared to the nonadaptive method. The average nodal CTV D{sub 95%} remains constant across the strategies, except for the gradient approach where a reduction of 7% is observed. However, a correction of the systematic shift reduced the problem, and the adaptive strategies remain robust against the prostate movement across the fraction. The bladder V{sub 55Gy} is reduced by 35% on average for the adaptive strategies. Conclusions: Because they offer increased CTV coverage and OAR sparing, adaptive methods may be suitable candidates for simple and efficient adaptive treatment strategies for prostate cancer. Margin reduction and systematic error correction in the prostate position improve the protection of the OAR and the dose coverage. A cumulative dose to simulate a complete treatment would show real effects and allow a better comparison between each method.« less

Development and experimental validation of computational methods to simulate abnormal thermal and structural environments

NASA Astrophysics Data System (ADS)

Moya, J. L.; Skocypec, R. D.; Thomas, R. K.

1993-09-01

Over the past 40 years, Sandia National Laboratories (SNL) has been actively engaged in research to improve the ability to accurately predict the response of engineered systems to abnormal thermal and structural environments. These engineered systems contain very hazardous materials. Assessing the degree of safety/risk afforded the public and environment by these engineered systems, therefore, is of upmost importance. The ability to accurately predict the response of these systems to accidents (to abnormal environments) is required to assess the degree of safety. Before the effect of the abnormal environment on these systems can be determined, it is necessary to ascertain the nature of the environment. Ascertaining the nature of the environment, in turn, requires the ability to physically characterize and numerically simulate the abnormal environment. Historically, SNL has demonstrated the level of safety provided by these engineered systems by either of two approaches: a purely regulatory approach, or by a probabilistic risk assessment (PRA). This paper will address the latter of the two approaches.

Hydrocarbons (jet fuel JP-8) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations.

PubMed

Tracey, Rebecca; Manikkam, Mohan; Guerrero-Bosagna, Carlos; Skinner, Michael K

2013-04-01

Environmental compounds have been shown to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a hydrocarbon mixture involving jet fuel (JP-8) promotes epigenetic transgenerational inheritance of disease. Gestating F0 generation female rats were transiently exposed during the fetal gonadal development period. The direct exposure F1 generation had an increased incidence of kidney abnormalities in both females and males, prostate and pubertal abnormalities in males, and primordial follicle loss and polycystic ovarian disease in females. The first transgenerational generation is the F3 generation, and the jet fuel lineage had an increased incidence of primordial follicle loss and polycystic ovarian disease in females, and obesity in both females and males. Analysis of the jet fuel lineage F3 generation sperm epigenome identified 33 differential DNA methylation regions, termed epimutations. Observations demonstrate hydrocarbons can promote epigenetic transgenerational inheritance of disease and sperm epimutations, potential biomarkers for ancestral exposures. Copyright © 2012 Elsevier Inc. All rights reserved.

Hydrocarbons (Jet Fuel JP-8) Induce Epigenetic Transgenerational Inheritance of Obesity, Reproductive Disease and Sperm Epimutations

PubMed Central

Tracey, Rebecca; Manikkam, Mohan; Guerrero-Bosagna, Carlos; Skinner, Michael K.

2012-01-01

Environmental compounds have been shown to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a hydrocarbon mixture involving jet fuel (JP-8) promotes epigenetic transgenerational inheritance of disease. Gestating F0 generation female rats were transiently exposed during the fetal gonadal development period. The direct exposure F1 generation had an increased incidence of kidney abnormalities in both females and males, prostate and pubertal abnormalities in males, and primordial follicle loss and polycystic ovarian disease in females. The first transgenerational generation is the F3 generation, and the jet fuel lineage had an increased incidence of primordial follicle loss and polycystic ovarian disease in females, and obesity in both females and males. Analysis of the jet fuel lineage F3 generation sperm epigenome identified 33 differential DNA methylation regions, termed epimutations. Observations demonstrate hydrocarbons can promote epigenetic transgenerational inheritance of disease and sperm epimutations, potential biomarkers for ancestral exposures. PMID:23453003

The use of collagen-based scaffolds to simulate prostate cancer bone metastases with potential for evaluating delivery of nanoparticulate gene therapeutics.

PubMed

Fitzgerald, Kathleen A; Guo, Jianfeng; Tierney, Erica G; Curtin, Caroline M; Malhotra, Meenakshi; Darcy, Raphael; O'Brien, Fergal J; O'Driscoll, Caitriona M

2015-10-01

Prostate cancer bone metastases are a leading cause of cancer-related death in men with current treatments offering only marginally improved rates of survival. Advances in the understanding of the genetic basis of prostate cancer provide the opportunity to develop gene-based medicines capable of treating metastatic disease. The aim of this work was to establish a 3D cell culture model of prostate cancer bone metastasis using collagen-based scaffolds, to characterise this model, and to assess the potential of the model to evaluate delivery of gene therapeutics designed to target bone metastases. Two prostate cancer cell lines (PC3 and LNCaP) were cultured in 2D standard culture and compared to 3D cell growth on three different collagen-based scaffolds (collagen and composites of collagen containing either glycosaminoglycan or nanohydroxyapatite). The 3D model was characterised for cell proliferation, viability and for matrix metalloproteinase (MMP) enzyme and Prostate Specific Antigen (PSA) secretion. Chemosensitivity to docetaxel treatment was assessed in 2D in comparison to 3D. Nanoparticles (NPs) containing siRNA formulated using a modified cyclodextrin were delivered to the cells on the scaffolds and gene silencing was quantified. Both prostate cancer cell lines actively infiltrated and proliferated on the scaffolds. Cell culture in 3D resulted in reduced levels of MMP1 and MMP9 secretion in PC3 cells. In contrast, LNCaP cells grown in 3D secreted elevated levels of PSA, particularly on the scaffold composed of collagen and glycosaminoglycans. Both cell lines grown in 3D displayed increased resistance to docetaxel treatment. The cyclodextrin.siRNA nanoparticles achieved cellular uptake and knocked down the endogenous GAPDH gene in the 3D model. In conclusion, development of a novel 3D cell culture model of prostate cancer bone metastasis has been initiated resulting, for the first time, in the successful delivery of gene therapeutics in a 3D in vitro model. Further enhancement of this model will help elucidate the pathogenesis of prostate cancer and also accelerate the design of effective therapies which can penetrate into the bone microenvironment for prostate cancer therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization of fibroblast-free CWR-R1ca castration-recurrent prostate cancer cell line.

PubMed

Shourideh, Mojgan; DePriest, Adam; Mohler, James L; Wilson, Elizabeth M; Koochekpour, Shahriar

2016-09-01

The previously established CWR-R1 cell line has been used as an in vitro model representing castration-recurrent prostate cancer. Microscopic observation of subconfluent cells demonstrated two distinct cellular morphologies: polygonal closely aggregated epithelial cells surrounded by bipolar fibroblastic cells with long processes. This study sought to establish and characterize a fibroblast-free derivative of the CWR-R1 cell line. The CWR-R1ca cell line was established from CWR-R1 cells by removing fibroblasts using multiple cycles of short-term trypsinization, cloning, and pooling single-cell colonies. Authentication of fibroblast-free CWR-R1ca cells was demonstrated by analyzing the expression of cytodifferentiation and prostate-associated markers, DNA and cytogenetic profiling, and growth pattern in the absence or presence of androgen. CWR-R1ca is an androgen-sensitive cell line that expresses the androgen receptor (AR) and its splice variant 7 and the luminal epithelia markers, CK-8, CK-18, and c-Met. CWR-R1fb fibroblasts isolated from CWR-R1 cells express AR, hepatocyte growth factor-α, and mouse β-actin but not AR-V7 or epithelial markers. Cytogenetic analysis of CWR-R1ca cells revealed a hyperdiploid male with numerical gains in chromosomes 1, 7, 8, 10, 11, and 12, deletion of one chromosome 2 allele, structural abnormalities that include der(1)t(1:4), der(4)t(2:4), der(10)t(4:10), and an unbalanced reciprocal translocation between chromosome 6 and 14. DNA-profiling revealed that CWR-R1ca cells had significant short-tandem repeat marker homology with CWR22Pc and CWR22Rv1 cell lines, which indicated lineage derivation from CWR22 prostate cancer xenografts. CWR-R1ca cells were responsive to the growth stimulatory effects of dihydrotestosterone (DHT) in the femtomolar range. This study establishes CWR-R1ca cells as a fibroblast-free derivative of the castration-recurrent CWR-R1 cell line. Prostate 76:1067-1077, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Silodosin for the treatment of clinical benign prostatic hyperplasia: safety, efficacy, and patient acceptability.

PubMed

Cho, Hee Ju; Yoo, Tag Keun

2014-01-01

α1-Adrenergic receptor antagonists are commonly used to treat male lower urinary tract symptoms and benign prostatic hyperplasia (BPH). We performed a literature search using PubMed, Medline via Ovid, Embase, and the Cochrane Library databases to identify studies on the treatment of BPH by silodosin. Silodosin is a novel α1-adrenergic receptor antagonist whose affinity for the α1A-adrenergic receptor is greater than that for the α1B-adrenergic receptor. Therefore, silodosin does not increase the incidence of blood pressure-related side effects, which may result from the inhibition of the α1B-adrenergic receptor. Patients receiving silodosin at a daily dose of 8 mg showed a significant improvement in the International Prostate Symptom Score and maximum urinary flow rate compared with those receiving a placebo. Silodosin also improved both storage and voiding symptoms, indicating that silodosin is effective, even during early phases of BPH treatment. Follow-up extension studies performed in the United States, Europe, and Asia demonstrated its long-term safety and efficacy. In the European study, silodosin significantly reduced nocturia compared to the placebo. Although retrograde or abnormal ejaculation was the most commonly reported symptom in these studies, only a few patients discontinued treatment. The incidence of adverse cardiovascular events was also very low. Evidence showing solid efficacy and cardiovascular safety profiles of silodosin will provide a good solution for the treatment of lower urinary tract symptoms associated with BPH in an increasingly aging society.

Silodosin for the treatment of clinical benign prostatic hyperplasia: safety, efficacy, and patient acceptability

PubMed Central

Cho, Hee Ju; Yoo, Tag Keun

2014-01-01

α1-Adrenergic receptor antagonists are commonly used to treat male lower urinary tract symptoms and benign prostatic hyperplasia (BPH). We performed a literature search using PubMed, Medline via Ovid, Embase, and the Cochrane Library databases to identify studies on the treatment of BPH by silodosin. Silodosin is a novel α1-adrenergic receptor antagonist whose affinity for the α1A-adrenergic receptor is greater than that for the α1B-adrenergic receptor. Therefore, silodosin does not increase the incidence of blood pressure-related side effects, which may result from the inhibition of the α1B-adrenergic receptor. Patients receiving silodosin at a daily dose of 8 mg showed a significant improvement in the International Prostate Symptom Score and maximum urinary flow rate compared with those receiving a placebo. Silodosin also improved both storage and voiding symptoms, indicating that silodosin is effective, even during early phases of BPH treatment. Follow-up extension studies performed in the United States, Europe, and Asia demonstrated its long-term safety and efficacy. In the European study, silodosin significantly reduced nocturia compared to the placebo. Although retrograde or abnormal ejaculation was the most commonly reported symptom in these studies, only a few patients discontinued treatment. The incidence of adverse cardiovascular events was also very low. Evidence showing solid efficacy and cardiovascular safety profiles of silodosin will provide a good solution for the treatment of lower urinary tract symptoms associated with BPH in an increasingly aging society. PMID:25328864

Assessment of prostate cancer detection with a visual-search human model observer

NASA Astrophysics Data System (ADS)

Sen, Anando; Kalantari, Faraz; Gifford, Howard C.

2014-03-01

Early staging of prostate cancer (PC) is a significant challenge, in part because of the small tumor sizes in- volved. Our long-term goal is to determine realistic diagnostic task performance benchmarks for standard PC imaging with single photon emission computed tomography (SPECT). This paper reports on a localization receiver operator characteristic (LROC) validation study comparing human and model observers. The study made use of a digital anthropomorphic phantom and one-cm tumors within the prostate and pelvic lymph nodes. Uptake values were consistent with data obtained from clinical In-111 ProstaScint scans. The SPECT simulation modeled a parallel-hole imaging geometry with medium-energy collimators. Nonuniform attenua- tion and distance-dependent detector response were accounted for both in the imaging and the ordered-subset expectation-maximization (OSEM) iterative reconstruction. The observer study made use of 2D slices extracted from reconstructed volumes. All observers were informed about the prostate and nodal locations in an image. Iteration number and the level of postreconstruction smoothing were study parameters. The results show that a visual-search (VS) model observer correlates better with the average detection performance of human observers than does a scanning channelized nonprewhitening (CNPW) model observer.

Performance of external and internal coil configurations for prostate investigations at 7 Tesla

PubMed Central

Metzger, Gregory J.; van de Moortele, Pierre-Francois; Akgun, Can; Snyder, Carl J.; Moeller, Steen; Strupp, John; Andersen, Peter; Shrivastava, Devashish; Vaughan, Tommy; Ugurbil, Kamil; Adriany, Gregor

2010-01-01

Three different coil configurations were evaluated through simulation and experimentally to determine safe operating limits and evaluate subject size dependent performance for prostate imaging at 7 Tesla. The coils included a transceiver endorectal coil (trERC), a 16 channel transceiver external surface array (trESA) and a trESA combined with a receive-only ERC (trESA+roERC). While the transmit B1 (B1+) homogeneity was far superior for the trESA, the maximum achievable B1+ is subject size dependent and limited by transmit chain losses and amplifier performance. For the trERC, limitations in transmit homogeneity greatly compromised image quality and limited coverage of the prostate. Despite these challenges, the high peak B1+ close to the trERC and subject size independent performance provides potential advantages especially for spectroscopic localization where high bandwidth RF pulses are required. On the receive side, the combined trESA+roERC provided the highest SNR and improved homogeneity over the trERC resulting in better visualization of the prostate and surrounding anatomy. In addition, the parallel imaging performance of the trESA+roERC holds strong promise for diffusion weighted imaging and dynamic contrast enhanced MRI. PMID:20740657

MO-G-17A-02: Computer Simulation Studies for On-Board Functional and Molecular Imaging of the Prostate Using a Robotic Multi-Pinhole SPECT System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, L; Duke University Medical Center, Durham, NC; Fudan University Shanghai Cancer Center, Shanghai

Purpose: To investigate prostate imaging onboard radiation therapy machines using a novel robotic, 49-pinhole Single Photon Emission Computed Tomography (SPECT) system. Methods: Computer-simulation studies were performed for region-of-interest (ROI) imaging using a 49-pinhole SPECT collimator and for broad cross-section imaging using a parallel-hole SPECT collimator. A male XCAT phantom was computersimulated in supine position with one 12mm-diameter tumor added in the prostate. A treatment couch was added to the phantom. Four-minute detector trajectories for imaging a 7cm-diameter-sphere ROI encompassing the tumor were investigated with different parameters, including pinhole focal length, pinhole diameter and trajectory starting angle. Pseudo-random Poisson noise wasmore » included in the simulated projection data, and SPECT images were reconstructed by OSEM with 4 subsets and up to 10 iterations. Images were evaluated by visual inspection, profiles, and Root-Mean- Square-Error (RMSE). Results: The tumor was well visualized above background by the 49-pinhole SPECT system with different pinhole parameters while it was not visible with parallel-hole SPECT imaging. Minimum RMSEs were 0.30 for 49-pinhole imaging and 0.41 for parallelhole imaging. For parallel-hole imaging, the detector trajectory from rightto- left yielded slightly lower RMSEs than that from posterior to anterior. For 49-pinhole imaging, near-minimum RMSEs were maintained over a broader range of OSEM iterations with a 5mm pinhole diameter and 21cm focal length versus a 2mm diameter pinhole and 18cm focal length. The detector with 21cm pinhole focal length had the shortest rotation radius averaged over the trajectory. Conclusion: On-board functional and molecular prostate imaging may be feasible in 4-minute scan times by robotic SPECT. A 49-pinhole SPECT system could improve such imaging as compared to broadcross-section parallel-hole collimated SPECT imaging. Multi-pinhole imaging can be improved by considering pinhole focal length, pinhole diameter, and trajectory starting angle. The project is supported by the NIH grant 5R21-CA156390.« less

Response of Human Prostate Cancer Cells to Mitoxantrone Treatment in Simulated Microgravity Environment

NASA Astrophysics Data System (ADS)

Zhang, Ye; Wu, Honglu

2012-07-01

RESPONSE OF HUMAN PROSTATE CANCER CELLS TO MITOXANTRONE TREATMENT IN SIMULATED MICROGRAVITY ENVIRONMENT Ye Zhang1,2, Christopher Edwards3, and Honglu Wu1 1 NASA-Johnson Space Center, Houston, TX 2 Wyle Integrated Science and Engineering Group, Houston, TX 3 Oregon State University, Corvallis, OR This study explores the changes in growth of human prostate cancer cells (LNCaP) and their response to the treatment of an antineoplastic agent, mitoxantrone, under the simulated microgravity condition. In comparison to static 1g, microgravity and simulated microgravity have been shown to alter global gene expression patterns and protein levels in various cultured cell models or animals. However, very little is known about the effect of altered gravity on the responses of cells to the treatment of drugs, especially chemotherapy drugs. To test the hypothesis that zero gravity would result in altered regulations of cells in response to antineoplastic agents, we cultured LNCaP cells in either a High Aspect Ratio Vessel (HARV) bioreactor at the rotating condition to model microgravity in space or in the static condition as control, and treated the cells with mitoxantrone. Cell growth, as well as expressions of oxidative stress related genes, were analyzed after the drug treatment. Compared to static 1g controls, the cells cultured in the simulated microgravity environment did not present significant differences in cell viability, growth rate, or cell cycle distribution. However, after mitoxantrone treatment, a significant proportion of bioreactor cultured cells became apoptotic or was arrested in G2. Several oxidative stress related genes also showed a higher expression level post mitoxantrone treatment. Our results indicate that simulated microgravity may alter the response of LNCaP cells to mitoxantrone treatment. Understanding the mechanisms by which cells respond to drugs differently in an altered gravity environment will be useful for the improvement of cancer treatment on the ground. This study explores the changes in growth of human prostate cancer cells (LNCaP) and their response to the treatment of an antineoplastic agent, mitoxantrone, under the simulated microgravity condition. In comparison to static 1g, microgravity and simulated microgravity have been shown to alter global gene expression patterns and protein levels in various cultured cell models or animals. However, very little is known about the effect of altered gravity on the responses of cells to the treatment of drugs, especially chemotherapy drugs. To test the hypothesis that zero gravity would result in altered regulations of cells in response to antineoplastic agents, we cultured LNCaP cells in either a High Aspect Ratio Vessel (HARV) bioreactor at the rotating condition to model microgravity in space or in the static condition as control, and treated the cells with mitoxantrone. Cell growth, as well as expressions of oxidative stress related genes, were analyzed after the drug treatment. Compared to static 1g controls, the cells cultured in the simulated microgravity environment did not present significant differences in cell viability, growth rate, or cell cycle distribution. However, after mitoxantrone treatment, a significant proportion of bioreactor cultured cells became apoptotic or was arrested in G2. Several oxidative stress related genes also showed a higher expression level post mitoxantrone treatment. Our results indicate that simulated microgravity may alter the response of LNCaP cells to mitoxantrone treatment. Understanding the mechanisms by which cells respond to drugs differently in an altered gravity environment will be useful for the improvement of cancer treatment on the ground.

Hierarchical clustering method for improved prostate cancer imaging in diffuse optical tomography

NASA Astrophysics Data System (ADS)

Kavuri, Venkaiah C.; Liu, Hanli

2013-03-01

We investigate the feasibility of trans-rectal near infrared (NIR) based diffuse optical tomography (DOT) for early detection of prostate cancer using a transrectal ultrasound (TRUS) compatible imaging probe. For this purpose, we designed a TRUS-compatible, NIR-based image system (780nm), in which the photo diodes were placed on the trans-rectal probe. DC signals were recorded and used for estimating the absorption coefficient. We validated the system using laboratory phantoms. For further improvement, we also developed a hierarchical clustering method (HCM) to improve the accuracy of image reconstruction with limited prior information. We demonstrated the method using computer simulations laboratory phantom experiments.

Optimization of b-value distribution for biexponential diffusion-weighted MR imaging of normal prostate.

PubMed

Jambor, Ivan; Merisaari, Harri; Aronen, Hannu J; Järvinen, Jukka; Saunavaara, Jani; Kauko, Tommi; Borra, Ronald; Pesola, Marko

2014-05-01

To determine the optimal b-value distribution for biexponential diffusion-weighted imaging (DWI) of normal prostate using both a computer modeling approach and in vivo measurements. Optimal b-value distributions for the fit of three parameters (fast diffusion Df, slow diffusion Ds, and fraction of fast diffusion f) were determined using Monte-Carlo simulations. The optimal b-value distribution was calculated using four individual optimization methods. Eight healthy volunteers underwent four repeated 3 Tesla prostate DWI scans using both 16 equally distributed b-values and an optimized b-value distribution obtained from the simulations. The b-value distributions were compared in terms of measurement reliability and repeatability using Shrout-Fleiss analysis. Using low noise levels, the optimal b-value distribution formed three separate clusters at low (0-400 s/mm2), mid-range (650-1200 s/mm2), and high b-values (1700-2000 s/mm2). Higher noise levels resulted into less pronounced clustering of b-values. The clustered optimized b-value distribution demonstrated better measurement reliability and repeatability in Shrout-Fleiss analysis compared with 16 equally distributed b-values. The optimal b-value distribution was found to be a clustered distribution with b-values concentrated in the low, mid, and high ranges and was shown to improve the estimation quality of biexponential DWI parameters of in vivo experiments. Copyright © 2013 Wiley Periodicals, Inc.

The Feasibility of Conformal Thermal Therapy with Transurethral Ultrasound Heating Applicators and MR Temperature Feedback

NASA Astrophysics Data System (ADS)

Choy, Vanessa; Tang, Kee; Wachsmuth, Jeff; Chopra, Rajiv; Bronskill, Michael

2006-05-01

Transurethral thermal therapy offers a minimally invasive alternative for the treatment of prostate diseases including benign prostate hyperplasia (BPH) and prostate cancer. Accurate heating of a targeted region of the gland can be achieved through the use of a rotating directional heating source incorporating planar ultrasound transducers, and the implementation of active temperature feedback along the beam direction during heating provided by magnetic resonance (MR) thermometry. The performance of this control method with practical spatial, temporal, and temperature resolution (such as angular alignment, spatial resolution, update rate for temperature feedback (imaging time), and the presence of noise) for thermal feedback using a clinical 1.5 T MR scanner was investigated in simulations. As expected, the control algorithm was most sensitive to the presence of noise, with noticeable degradation in its performance above ±2°C of temperature uncertainty. With respect to temporal resolution, acceptable performance was achieved at update rates of 5s or faster. The control algorithm was relatively insensitive to reduced spatial resolution due to the broad nature of the heating pattern produced by the heating applicator, this provides an opportunity to improve signal-to-noise ratio (SNR). The overall simulation results confirm that existing clinical 1.5T MR imagers are capable of providing adequate temperature feedback for transurethral thermal therapy without special pulse sequences or enhanced imaging hardware.

Prevention. How much harm? How much benefit? 3. Physical, psychological and social harm.

PubMed Central

Marshall, K G

1996-01-01

Harm caused by preventive programs may be physical, psychological, social or, if informed consent has not been obtained, ethical. Adverse effects of preventive screening programs may occur at any of the three levels of the "screening cascade", the screening procedure itself, the investigation of abnormal results of screening tests or the treatment of detected abnormalities or diseases. The greatest harm occurs at the second and third levels. Examples of procedures that may cause physical harm are venipuncture, mammography, colonoscopy, breast biopsy, transrectal ultrasonography, prostate biopsy, weight-reducing and cholesterol-lowering diets and radical prostatectomy. The psychological and social harm of preventive programs involves anticipated discomfort or perception of adverse effects of preventive interventions; unpleasant interactions with health care workers, time required for preventive programs, excessive overall awareness of health, anxiety over the results of a screening test implications of a positive screening test, consequences of being labelled as "sick" or "at risk," psychopathologic effects induced directly by preventive programs and, in the case of a false-negative test result, false assurance of disease-free status. Since the positive predictive value of screening tests in the general population is always low, most abnormal test results are "false-positive," these engender a great deal of psychological discuss among patients. PMID:8800074

Complex patterns of abnormal heartbeats

NASA Technical Reports Server (NTRS)

Schulte-Frohlinde, Verena; Ashkenazy, Yosef; Goldberger, Ary L.; Ivanov, Plamen Ch; Costa, Madalena; Morley-Davies, Adrian; Stanley, H. Eugene; Glass, Leon

2002-01-01

Individuals having frequent abnormal heartbeats interspersed with normal heartbeats may be at an increased risk of sudden cardiac death. However, mechanistic understanding of such cardiac arrhythmias is limited. We present a visual and qualitative method to display statistical properties of abnormal heartbeats. We introduce dynamical "heartprints" which reveal characteristic patterns in long clinical records encompassing approximately 10(5) heartbeats and may provide information about underlying mechanisms. We test if these dynamics can be reproduced by model simulations in which abnormal heartbeats are generated (i) randomly, (ii) at a fixed time interval following a preceding normal heartbeat, or (iii) by an independent oscillator that may or may not interact with the normal heartbeat. We compare the results of these three models and test their limitations to comprehensively simulate the statistical features of selected clinical records. This work introduces methods that can be used to test mathematical models of arrhythmogenesis and to develop a new understanding of underlying electrophysiologic mechanisms of cardiac arrhythmia.

Assessing the Clinical Impact of Approximations in Analytical Dose Calculations for Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schuemann, Jan, E-mail: jschuemann@mgh.harvard.edu; Giantsoudi, Drosoula; Grassberger, Clemens

2015-08-01

Purpose: To assess the impact of approximations in current analytical dose calculation methods (ADCs) on tumor control probability (TCP) in proton therapy. Methods: Dose distributions planned with ADC were compared with delivered dose distributions as determined by Monte Carlo simulations. A total of 50 patients were investigated in this analysis with 10 patients per site for 5 treatment sites (head and neck, lung, breast, prostate, liver). Differences were evaluated using dosimetric indices based on a dose-volume histogram analysis, a γ-index analysis, and estimations of TCP. Results: We found that ADC overestimated the target doses on average by 1% to 2%more » for all patients considered. The mean dose, D95, D50, and D02 (the dose value covering 95%, 50% and 2% of the target volume, respectively) were predicted within 5% of the delivered dose. The γ-index passing rate for target volumes was above 96% for a 3%/3 mm criterion. Differences in TCP were up to 2%, 2.5%, 6%, 6.5%, and 11% for liver and breast, prostate, head and neck, and lung patients, respectively. Differences in normal tissue complication probabilities for bladder and anterior rectum of prostate patients were less than 3%. Conclusion: Our results indicate that current dose calculation algorithms lead to underdosage of the target by as much as 5%, resulting in differences in TCP of up to 11%. To ensure full target coverage, advanced dose calculation methods like Monte Carlo simulations may be necessary in proton therapy. Monte Carlo simulations may also be required to avoid biases resulting from systematic discrepancies in calculated dose distributions for clinical trials comparing proton therapy with conventional radiation therapy.« less

Modeling Clinical Outcomes in Prostate Cancer: Application and Validation of the Discrete Event Simulation Approach.

PubMed

Pan, Feng; Reifsnider, Odette; Zheng, Ying; Proskorovsky, Irina; Li, Tracy; He, Jianming; Sorensen, Sonja V

2018-04-01

Treatment landscape in prostate cancer has changed dramatically with the emergence of new medicines in the past few years. The traditional survival partition model (SPM) cannot accurately predict long-term clinical outcomes because it is limited by its ability to capture the key consequences associated with this changing treatment paradigm. The objective of this study was to introduce and validate a discrete-event simulation (DES) model for prostate cancer. A DES model was developed to simulate overall survival (OS) and other clinical outcomes based on patient characteristics, treatment received, and disease progression history. We tested and validated this model with clinical trial data from the abiraterone acetate phase III trial (COU-AA-302). The model was constructed with interim data (55% death) and validated with the final data (96% death). Predicted OS values were also compared with those from the SPM. The DES model's predicted time to chemotherapy and OS are highly consistent with the final observed data. The model accurately predicts the OS hazard ratio from the final data cut (predicted: 0.74; 95% confidence interval [CI] 0.64-0.85 and final actual: 0.74; 95% CI 0.6-0.88). The log-rank test to compare the observed and predicted OS curves indicated no statistically significant difference between observed and predicted curves. However, the predictions from the SPM based on interim data deviated significantly from the final data. Our study showed that a DES model with properly developed risk equations presents considerable improvements to the more traditional SPM in flexibility and predictive accuracy of long-term outcomes. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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 distributions with the highest accuracy and the least bias compared to SECT. When imaging noise is considered, benefits of DECT are noticeable if important calcifications are found within the prostate.

Fast patient-specific Monte Carlo brachytherapy dose calculations via the correlated sampling variance reduction technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sampson, Andrew; Le Yi; Williamson, Jeffrey F.

2012-02-15

Purpose: To demonstrate potential of correlated sampling Monte Carlo (CMC) simulation to improve the calculation efficiency for permanent seed brachytherapy (PSB) implants without loss of accuracy. Methods: CMC was implemented within an in-house MC code family (PTRAN) and used to compute 3D dose distributions for two patient cases: a clinical PSB postimplant prostate CT imaging study and a simulated post lumpectomy breast PSB implant planned on a screening dedicated breast cone-beam CT patient exam. CMC tallies the dose difference, {Delta}D, between highly correlated histories in homogeneous and heterogeneous geometries. The heterogeneous geometry histories were derived from photon collisions sampled inmore » a geometrically identical but purely homogeneous medium geometry, by altering their particle weights to correct for bias. The prostate case consisted of 78 Model-6711 {sup 125}I seeds. The breast case consisted of 87 Model-200 {sup 103}Pd seeds embedded around a simulated lumpectomy cavity. Systematic and random errors in CMC were unfolded using low-uncertainty uncorrelated MC (UMC) as the benchmark. CMC efficiency gains, relative to UMC, were computed for all voxels, and the mean was classified in regions that received minimum doses greater than 20%, 50%, and 90% of D{sub 90}, as well as for various anatomical regions. Results: Systematic errors in CMC relative to UMC were less than 0.6% for 99% of the voxels and 0.04% for 100% of the voxels for the prostate and breast cases, respectively. For a 1 x 1 x 1 mm{sup 3} dose grid, efficiency gains were realized in all structures with 38.1- and 59.8-fold average gains within the prostate and breast clinical target volumes (CTVs), respectively. Greater than 99% of the voxels within the prostate and breast CTVs experienced an efficiency gain. Additionally, it was shown that efficiency losses were confined to low dose regions while the largest gains were located where little difference exists between the homogeneous and heterogeneous doses. On an AMD 1090T processor, computing times of 38 and 21 sec were required to achieve an average statistical uncertainty of 2% within the prostate (1 x 1 x 1 mm{sup 3}) and breast (0.67 x 0.67 x 0.8 mm{sup 3}) CTVs, respectively. Conclusions: CMC supports an additional average 38-60 fold improvement in average efficiency relative to conventional uncorrelated MC techniques, although some voxels experience no gain or even efficiency losses. However, for the two investigated case studies, the maximum variance within clinically significant structures was always reduced (on average by a factor of 6) in the therapeutic dose range generally. CMC takes only seconds to produce an accurate, high-resolution, low-uncertainly dose distribution for the low-energy PSB implants investigated in this study.« less

Computerized Planning of Cryosurgery Using Bubble Packing: An Experimental Validation on a Phantom Material

PubMed Central

Rossi, Michael R.; Tanaka, Daigo; Shimada, Kenji; Rabin, Yoed

2009-01-01

The current study focuses on experimentally validating a planning scheme based on the so-called bubble-packing method. This study is a part of an ongoing effort to develop computerized planning tools for cryosurgery, where bubble packing has been previously developed as a means to find an initial, uniform distribution of cryoprobes within a given domain; the so-called force-field analogy was then used to move cryoprobes to their optimum layout. However, due to the high quality of the cryoprobes’ distribution, suggested by bubble packing and its low computational cost, it has been argued that a planning scheme based solely on bubble packing may be more clinically relevant. To test this argument, an experimental validation is performed on a simulated cross-section of the prostate, using gelatin solution as a phantom material, proprietary liquid-nitrogen based cryoprobes, and a cryoheater to simulate urethral warming. Experimental results are compared with numerically simulated temperature histories resulting from planning. Results indicate an average disagreement of 0.8 mm in identifying the freezing front location, which is an acceptable level of uncertainty in the context of prostate cryosurgery imaging. PMID:19885373

Tissue mimicking simulations for temporal enhanced ultrasound-based tissue typing

NASA Astrophysics Data System (ADS)

Bayat, Sharareh; Imani, Farhad; Gerardo, Carlos D.; Nir, Guy; Azizi, Shekoofeh; Yan, Pingkun; Tahmasebi, Amir; Wilson, Storey; Iczkowski, Kenneth A.; Lucia, M. Scott; Goldenberg, Larry; Salcudean, Septimiu E.; Mousavi, Parvin; Abolmaesumi, Purang

2017-03-01

Temporal enhanced ultrasound (TeUS) is an imaging approach where a sequence of temporal ultrasound data is acquired and analyzed for tissue typing. Previously, in a series of in vivo and ex vivo studies we have demonstrated that, this approach is effective for detecting prostate and breast cancers. Evidences derived from our experiments suggest that both ultrasound-signal related factors such as induced heat and tissue-related factors such as the distribution and micro-vibration of scatterers lead to tissue typing information in TeUS. In this work, we simulate mechanical micro-vibrations of scatterers in tissue-mimicking phantoms that have various scatterer densities reflecting benign and cancerous tissue structures. Finite element modeling (FEM) is used for this purpose where the vertexes are scatterers representing cell nuclei. The initial positions of scatterers are determined by the distribution of nuclei segmented from actual digital histology scans of prostate cancer patients. Subsequently, we generate ultrasound images of the simulated tissue structure using the Field II package resulting in a temporal enhanced ultrasound. We demonstrate that the micro-vibrations of scatterers are captured by temporal ultrasound data and this information can be exploited for tissue typing.

Neurovascular bundle–sparing radiotherapy for prostate cancer using MRI-CT registration: A dosimetric feasibility study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cassidy, R.J., E-mail: richardjcassidy@emory.edu; Yang, X.; Liu, T.

Purpose: Sexual dysfunction after radiotherapy for prostate cancer remains an important late adverse toxicity. The neurovascular bundles (NVB) that lie posterolaterally to the prostate are typically spared during prostatectomy, but in traditional radiotherapy planning they are not contoured as an organ-at-risk with dose constraints. Our goal was to determine the dosimetric feasibility of “NVB-sparing” prostate radiotherapy while still delivering adequate dose to the prostate. Methods: Twenty-five consecutive patients with prostate cancer (with no extraprostatic disease on pelvic magnetic resonance imaging [MRI]) who that were treated with external beam radiotherapy, with the same primary planning target volume margins, to a dosemore » of 79.2 Gy were evaluated. Pelvic MRI and simulation computed tomography scans were registered using dedicated software to allow for bilateral NVB target delineation on T2-weighted MRI. A volumetric modulated arc therapy plan was generated using the NVB bilaterally with 2 mm margin as an organ to spare and compared to the patient’s previously delivered plan. Dose-volume histogram endpoints for NVB, rectum, bladder, and planning target volume 79.2 were compared between the 2 plans using a 2-tailed paired t-test. Results: The V70 for the NVB was significantly lower on the NVB-sparing plan (p <0.01), while rectum and bladder endpoints were similar. Target V100% was similar but V{sub 105%} was higher for the NVB-sparing plans (p <0.01). Conclusions: “NVB-sparing” radiotherapy is dosimetrically feasible using CT-MRI registration, and for volumetric modulated arc therapy technology — target coverage is acceptable without increased dose to other normal structures, but with higher target dose inhomogeneity. The clinical impact of “NVB-sparing” radiotherapy is currently under study at our institution.« less

Tissue mimicking materials for the detection of prostate cancer using shear wave elastography: a validation study.

PubMed

Cao, Rui; Huang, Zhihong; Varghese, Tomy; Nabi, Ghulam

2013-02-01

Quantification of stiffness changes may provide important diagnostic information and aid in the early detection of cancers. Shear wave elastography is an imaging technique that assesses tissue stiffness using acoustic radiation force as an alternate to manual palpation reported previously with quasistatic elastography. In this study, the elastic properties of tissue mimicking materials, including agar, polyacrylamide (PAA), and silicone, are evaluated with an objective to determine material characteristics which resemble normal and cancerous prostate tissue. Acoustic properties and stiffness of tissue mimicking phantoms were measured using compressional mechanical testing and shear wave elastography using supersonic shear imaging. The latter is based on the principles of shear waves generated using acoustic radiation force. The evaluation included tissue mimicking materials (TMMs) within the prostate at different positions and sizes that could mimic cancerous and normal prostate tissue. Patient data on normal and prostate cancer tissues quantified using biopsy histopathology were used to validate the findings. Pathologist reports on histopathology were blinded to mechanical testing and elastographic findings. Young's modulus values of 86.2 ± 4.5 and 271.5 ± 25.7 kPa were obtained for PAA mixed with 2% Al(2)O(3) particles and silicone, respectively. Young's modulus of TMMs from mechanical compression testing showed a clear trend of increasing stiffness with an increasing percentage of agar. The silicone material had higher stiffness values when compared with PAA with Al(2)O(3). The mean Young's modulus value in cancerous tissue was 90.5 ± 4.5 kPa as compared to 93.8 ± 4.4 and 86.2 ± 4.5 kPa obtained with PAA with 2% Al(2)O(3) phantom at a depth of 52.4 and 36.6 mm, respectively. PAA mixed with Al(2)O(3) provides the most suitable tissue mimicking material for prostate cancer tumor material, while agar could form the surrounding background to simulate normal prostate tissue.

Interactive deformation registration of endorectal prostate MRI using ITK thin plate splines.

PubMed

Cheung, M Rex; Krishnan, Karthik

2009-03-01

Magnetic resonance imaging with an endorectal coil allows high-resolution imaging of prostate cancer and the surrounding normal organs. These anatomic details can be used to direct radiotherapy. However, organ deformation introduced by the endorectal coil makes it difficult to register magnetic resonance images for treatment planning. In this study, plug-ins for the volume visualization software VolView were implemented on the basis of algorithms from the National Library of Medicine's Insight Segmentation and Registration Toolkit (ITK). Magnetic resonance images of a phantom simulating human pelvic structures were obtained with and without the endorectal coil balloon inflated. The prostate not deformed by the endorectal balloon was registered to the deformed prostate using an ITK thin plate spline (TPS). This plug-in allows the use of crop planes to limit the deformable registration in the region of interest around the prostate. These crop planes restricted the support of the TPS to the area around the prostate, where most of the deformation occurred. The region outside the crop planes was anchored by grid points. The TPS was more accurate in registering the local deformation of the prostate compared with a TPS variant, the elastic body spline. The TPS was also applied to register an in vivo T(2)-weighted endorectal magnetic resonance image. The intraprostatic tumor was accurately registered. This could potentially guide the boosting of intraprostatic targets. The source and target landmarks were placed graphically. This TPS plug-in allows the registration to be undone. The landmarks could be added, removed, and adjusted in real time and in three dimensions between repeated registrations. This interactive TPS plug-in allows a user to obtain a high level of accuracy satisfactory to a specific application efficiently. Because it is open-source software, the imaging community will be able to validate and improve the algorithm.

TH-A-BRF-08: Deformable Registration of MRI and CT Images for MRI-Guided Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhong, H; Wen, N; Gordon, J

2014-06-15

Purpose: To evaluate the quality of a commercially available MRI-CT image registration algorithm and then develop a method to improve the performance of this algorithm for MRI-guided prostate radiotherapy. Methods: Prostate contours were delineated on ten pairs of MRI and CT images using Eclipse. Each pair of MRI and CT images was registered with an intensity-based B-spline algorithm implemented in Velocity. A rectangular prism that contains the prostate volume was partitioned into a tetrahedral mesh which was aligned to the CT image. A finite element method (FEM) was developed on the mesh with the boundary constraints assigned from the Velocitymore » generated displacement vector field (DVF). The resultant FEM displacements were used to adjust the Velocity DVF within the prism. Point correspondences between the CT and MR images identified within the prism could be used as additional boundary constraints to enforce the model deformation. The FEM deformation field is smooth in the interior of the prism, and equal to the Velocity displacements at the boundary of the prism. To evaluate the Velocity and FEM registration results, three criteria were used: prostate volume conservation and center consistence under contour mapping, and unbalanced energy of their deformation maps. Results: With the DVFs generated by the Velocity and FEM simulations, the prostate contours were warped from MRI to CT images. With the Velocity DVFs, the prostate volumes changed 10.2% on average, in contrast to 1.8% induced by the FEM DVFs. The average of the center deviations was 0.36 and 0.27 cm, and the unbalance energy was 2.65 and 0.38 mJ/cc3 for the Velocity and FEM registrations, respectively. Conclusion: The adaptive FEM method developed can be used to reduce the error of the MIbased registration algorithm implemented in Velocity in the prostate region, and consequently may help improve the quality of MRI-guided radiation therapy.« less

Tissue mimicking materials for the detection of prostate cancer using shear wave elastography: A validation study

PubMed Central

Cao, Rui; Huang, Zhihong; Varghese, Tomy; Nabi, Ghulam

2013-01-01

Purpose: Quantification of stiffness changes may provide important diagnostic information and aid in the early detection of cancers. Shear wave elastography is an imaging technique that assesses tissue stiffness using acoustic radiation force as an alternate to manual palpation reported previously with quasistatic elastography. In this study, the elastic properties of tissue mimicking materials, including agar, polyacrylamide (PAA), and silicone, are evaluated with an objective to determine material characteristics which resemble normal and cancerous prostate tissue. Methods: Acoustic properties and stiffness of tissue mimicking phantoms were measured using compressional mechanical testing and shear wave elastography using supersonic shear imaging. The latter is based on the principles of shear waves generated using acoustic radiation force. The evaluation included tissue mimicking materials (TMMs) within the prostate at different positions and sizes that could mimic cancerous and normal prostate tissue. Patient data on normal and prostate cancer tissues quantified using biopsy histopathology were used to validate the findings. Pathologist reports on histopathology were blinded to mechanical testing and elastographic findings. Results: Young's modulus values of 86.2 ± 4.5 and 271.5 ± 25.7 kPa were obtained for PAA mixed with 2% Al2O3 particles and silicone, respectively. Young's modulus of TMMs from mechanical compression testing showed a clear trend of increasing stiffness with an increasing percentage of agar. The silicone material had higher stiffness values when compared with PAA with Al2O3. The mean Young's modulus value in cancerous tissue was 90.5 ± 4.5 kPa as compared to 93.8 ± 4.4 and 86.2 ± 4.5 kPa obtained with PAA with 2% Al2O3 phantom at a depth of 52.4 and 36.6 mm, respectively. Conclusions: PAA mixed with Al2O3 provides the most suitable tissue mimicking material for prostate cancer tumor material, while agar could form the surrounding background to simulate normal prostate tissue. PMID:23387774

Experiment K-7-16: Effects of Microgravity or Simulated Launch on Testicular Function in Rats

NASA Technical Reports Server (NTRS)

Amann, R. P.; Clemens, J. W.; Deaver, D.; Folmer, J.; Zirkin, B.; Veeramachaneni, D. N. R.; Grills, G. S.; Gruppi, C. M.; Wolgemuth, D.; Serova, L. V.;

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moteabbed, M; Trofimov, A; Sharp, G

Purpose: To investigate the impact of anatomy/setup variations on standard vs. hypofractionated anterolateral pencil beam scanning (PBS) proton therapy for prostate cancer. Methods: Six prostate cancer patients treated with double-scattering proton therapy, who underwent weekly verification CT scans were selected. Implanted fiducials were used for localization, and endorectal balloons for immobilization. New PBS plans using combination of lateral and anterior-oblique (AO) (±35 deg) beams were created. AO beams were added to spare the femoral heads during hypofractionation. Lateral beams delivered 50.4 Gy(RBE) to prostate plus 5-15mm of seminal vesicles and AO beams 28.8 Gy(RBE) to prostate, in 44 fractions. PTVmore » was laterally expanded by 2.5% to account for range uncertainty. No range margins were applied for AO beams, assuming delivery with in-vivo range verification. Field-specific apertures with 1.2cm margin were used. Spot size was ∼9.5mm sigma for 172MeV @isocenter in air. Plans were optimized as single-field-uniform-dose with ∼5% maximum non-uniformity. The planned dose was recomputed on each weekly CT after aligning the fiducials with the simulation CT, scaled and accumulated via deformable image registration. Hypofractionated treatments with 12 and 5 fractions were considered. Equivalent doses were calculated for prostate (α/β= 1.5Gy), bladder and rectum (α/β= 3Gy). Results: The biological equivalent prostate dose was 86.2 and 92.9 Gyeq for the hypofractionation scenarios at 4.32 and 7.35 Gy/fx, respectively. The equivalent prostate D98 was degraded by on average 2.7 Gyeq for standard, and 3.1 and 4.0 Gyeq for the hypofractionated plans after accumulation. Differences between accumulated and planned Dmean/D2/EUD were generally reduced when reducing the number of fractions for bladder and rectum. The average Dmean/D2/EUD differences over all patients and organs-at-risk were 0.74/4.0/9.23, 0.49/3.64/5.51, 0.37/3.21/3.49 Gyeq for 44, 12 and 5 fractions. Conclusion: Hypofractionation makes proton therapy of prostate more susceptible to interfractional motion-induced target dose degradation compared to the standard fractionation.« less

Transurethral light delivery for prostate photoacoustic imaging

NASA Astrophysics Data System (ADS)

Lediju Bell, Muyinatu A.; Guo, Xiaoyu; Song, Danny Y.; Boctor, Emad M.

2015-03-01

Photoacoustic imaging has broad clinical potential to enhance prostate cancer detection and treatment, yet it is challenged by the lack of minimally invasive, deeply penetrating light delivery methods that provide sufficient visualization of targets (e.g., tumors, contrast agents, brachytherapy seeds). We constructed a side-firing fiber prototype for transurethral photoacoustic imaging of prostates with a dual-array (linear and curvilinear) transrectal ultrasound probe. A method to calculate the surface area and, thereby, estimate the laser fluence at this fiber tip was derived, validated, applied to various design parameters, and used as an input to three-dimensional Monte Carlo simulations. Brachytherapy seeds implanted in phantom, ex vivo, and in vivo canine prostates at radial distances of 5 to 30 mm from the urethra were imaged with the fiber prototype transmitting 1064 nm wavelength light with 2 to 8 mJ pulse energy. Prebeamformed images were displayed in real time at a rate of 3 to 5 frames per second to guide fiber placement and beamformed offline. A conventional delay-and-sum beamformer provided decreasing seed contrast (23 to 9 dB) with increasing urethra-to-target distance, while the short-lag spatial coherence beamformer provided improved and relatively constant seed contrast (28 to 32 dB) regardless of distance, thus improving multitarget visualization in single and combined curvilinear images acquired with the fiber rotating and the probe fixed. The proposed light delivery and beamforming methods promise to improve key prostate cancer detection and treatment strategies.

Evaluation of contemporary prostate and urothelial lineage biomarkers in a consecutive cohort of poorly differentiated bladder neck carcinomas.

PubMed

Mohanty, Sambit K; Smith, Steven C; Chang, Elena; Luthringer, Daniel J; Gown, Allen M; Aron, Manju; Amin, Mahul B

2014-08-01

New immunohistochemical (IHC) markers of urothelial carcinoma (UCa) and prostatic adenocarcinoma (PCa) have emerged in recent years, yet comparative studies to establish markers remain lacking. We aimed to identify an effective but parsimonious approach for poorly differentiated bladder neck lesions, to establish a best practice panel approach in a setting simulating prospective use. We tested the performance of a panel of IHC markers on whole sections of a consecutive cohort of transurethral resection specimens of poorly differentiated, challenging bladder neck resections (n=36). In the setting of poorly differentiated bladder neck carcinomas, biomarker sensitivities for UCa were as follows: GATA3, 100%; S100P, 88%; p63, 75%; and cytokeratin (CK) 5/6, 56%; specificities of each were 100%. CK7 and CK20 showed sensitivities of 75% and 63%, though these were only 85% and 80% specific. For PCa markers, NKX3.1, p501S, prostate-specific membrane antigen, and androgen receptor (AR) each showed 100% sensitivity, outperforming ERG (35%) and prostate-specific antigen (PSA; 25%). All the prostate histogenesis markers were 100% specific, except for AR, which was positive in 13% of the UCa cases. Novel IHC markers show improved diagnostic performance that enables positive and negative support for identifying histogenesis with the use of as few as two markers for this critical therapeutic distinction. PSA underperforms newer markers. Copyright© by the American Society for Clinical Pathology.

In vivo dosimetry using a linear Mosfet-array dosimeter to determine the urethra dose in 125I permanent prostate implants.

PubMed

Bloemen-van Gurp, Esther J; Murrer, Lars H P; Haanstra, Björk K C; van Gils, Francis C J M; Dekker, Andre L A J; Mijnheer, Ben J; Lambin, Philippe

2009-01-01

In vivo dosimetry during brachytherapy of the prostate with (125)I seeds is challenging because of the high dose gradients and low photon energies involved. We present the results of a study using metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters to evaluate the dose in the urethra after a permanent prostate implantation procedure. Phantom measurements were made to validate the measurement technique, determine the measurement accuracy, and define action levels for clinical measurements. Patient measurements were performed with a MOSFET array in the urinary catheter immediately after the implantation procedure. A CT scan was performed, and dose values, calculated by the treatment planning system, were compared to in vivo dose values measured with MOSFET dosimeters. Corrections for temperature dependence of the MOSFET array response and photon attenuation in the catheter on the in vivo dose values are necessary. The overall uncertainty in the measurement procedure, determined in a simulation experiment, is 8.0% (1 SD). In vivo dose values were obtained for 17 patients. In the high-dose region (> 100 Gy), calculated and measured dose values agreed within 1.7% +/- 10.7% (1 SD). In the low-dose region outside the prostate (< 100 Gy), larger deviations occurred. MOSFET detectors are suitable for in vivo dosimetry during (125)I brachytherapy of prostate cancer. An action level of +/- 16% (2 SD) for detection of errors in the implantation procedure is achievable after validation of the detector system and measurement conditions.

Deciding on PSA-screening - Quality of current consumer information on the Internet.

PubMed

Korfage, Ida J; van den Bergh, Roderick C N; Essink-Bot, Marie-Louise

2010-11-01

Given that screening for prostate cancer has the potential to reduce prostate cancer mortality at the expense of considerable overdiagnosis and overtreatment, the availability of core consumer information - correct, balanced and supportive of autonomous decision-making - is a must. We assessed the quality of consumer information available through the Internet per November 2009 and its possible contribution to informed decision-making by potential screenees. Consumer information on PSA-screening was sought through the Internet in November 2009. Materials had to be targeted at potential consumers, offered by not-for-profit organisations, released in 2005 or after, in English or Dutch. Per material 2 of the authors assessed independently from each other whether standardised pre-defined topics were addressed, whether the content was correct and which approach was taken towards the decision-making process about uptake. Twenty-three materials were included, of which 11 were released (shortly) after the results of 2 large randomized-controlled trials (RCTs) that evaluated the effectiveness of screening for prostate cancer had been published in March 2009. That a PSA-test result can be abnormal because of non-cancerous conditions (false positive) and that it may miss prostate cancer (false negative) was not addressed in 2/23 and 8/23 materials, respectively. The risk of overdiagnosis and overtreatment was not mentioned in 6 out of 23. PSA-screening was presented as a usual thing to do in some materials, whereas other materials emphasised the voluntary nature of PSA-screening ('it is your decision'). The content of 19/23 materials was considered sufficiently informative according to the pre-defined criteria, 12/23 materials were considered supportive of informed decision-making by men. Most materials of not-for-profit organizations supplied adequate information about PSA-screening, whilst the degree of persuasion towards uptake reflected variations in opinions on men's autonomy regarding their own health. Copyright © 2010 Elsevier Ltd. All rights reserved.

Metabolomic profiling of prostate cancer by matrix assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry imaging using Matrix Coating Assisted by an Electric Field (MCAEF).

PubMed

Wang, Xiaodong; Han, Jun; Hardie, Darryl B; Yang, Juncong; Pan, Jingxi; Borchers, Christoph H

2017-07-01

In this work, we combined the use of two MALDI matrices (quercetin and 9-aminoacridine), a recently developed new matrix coating technique - matrix coating assisted by an electric field (MCAEF), and matrix-assisted laser desorption/ionization - Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICRMS) to detect and image endogenous compounds in the cancerous and non-cancerous regions of three human prostate cancer (stage II) tissue specimens. After three rounds of imaging data acquisitions (i.e., quercetin for positive and negative ion detection and 9-aminoacridine for negative ion detection), and metabolite identification, a total of 1091 metabolites including 1032 lipids and 59 other metabolites were routinely detected and successfully localized. Of these compounds, 250 and 217 were only detected in either the cancerous or the non-cancerous regions respectively, although we cannot rule out the presence of these metabolites at concentrations below the detection limit. In addition, 152 of the other 624 metabolites showed differential distributions (p<0.05, t-test) between the two regions of the tissues. Further studies on a larger number of clinical specimens will need to be carried out to confirm this large number of apparently cancer-related metabolites. The successful determination of the spatial locations and abundances of these endogenous biomolecules indicated significant metabolism abnormalities - e.g., increased energy charge and under-expression of neutral acyl glycerides, in the prostate cancer samples. To our knowledge, this work has resulted in MALDI-MS imaging of the largest group of metabolites in prostate cancer thus far and demonstrated the importance of using complementary matrices for comprehensive metabolomic imaging by MALDI-MS. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann. Copyright © 2017 Elsevier B.V. All rights reserved.

Locally Advanced Prostate Cancer: Three-Dimensional Magnetic Resonance Spectroscopy to Monitor Prostate Response to Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valentini, Anna Lia, E-mail: alvalentini@rm.unicatt.it; Gui, Benedetta; D'Agostino, Giuseppe Roberto

2012-11-01

Purpose: To correlate results of three-dimensional magnetic resonance spectroscopic imaging (MRSI) with prostate-specific antigen (PSA) levels and time since external beam irradiation (EBRT) in patients treated with long-term hormone therapy (HT) and EBRT for locally advanced disease to verify successful treatment by documenting the achievement of metabolic atrophy (MA). Methods and Materials: Between 2006 and 2008, 109 patients were consecutively enrolled. MA was assessed by choline and citrate peak area-to-noise-ratio <5:1. Cancerous metabolism (CM) was defined by choline-to-creatine ratio >1.5:1 or choline signal-to-noise-ratio >5:1. To test the strength of association between MRSI results and the time elapsed since EBRT (TEFRT),more » PSA levels, Gleason score (GS), and stage, logistic regression (LR) was performed. p value <0.05 was statistically significant. The patients' outcomes were verified in 2011. Results: MRSI documented MA in 84 of 109 and CM in 25 of 109 cases. LR showed that age, GS, stage, and initial and recent PSA had no significant impact on MRSI results which were significantly related to PSA values at the time of MRSI and to TEFRT. Patients were divided into three groups according to TEFRT: <1 year, 1-2 years, and >2 years. MA was detected in 54.1% of patients of group 1, 88.9% of group 2, and in 94.5% of group 3 (100% when PSA nadir was reached). CM was detected in 50% of patients with reached PSA nadir in group 1. Local relapse was found in 3 patients previously showing CM at long TEFRT. Conclusion: MA detection, indicative of successful treatment because growth of normal or abnormal cells cannot occur without metabolism, increases with decreasing PSA levels and increasing time on HT after EBRT. This supports long-term HT in advanced prostate cancer. Larger study series are needed to assess whether MRSI could predict local relapse by detecting CM at long TEFRT.« less

Pathogenesis of Bladder Calculi in the Presence of Urinary Stasis

PubMed Central

Childs, M. Adam; Mynderse, Lance A.; Rangel, Laureano J.; Wilson, Torrence M.; Lingeman, James E.; Krambeck, Amy E.

2013-01-01

Purpose Although minimal evidence exists, bladder calculi in men with benign prostatic hyperplasia are thought to be secondary to bladder outlet obstruction induced urinary stasis. We performed a prospective, multi-institutional clinical trial to determine whether metabolic differences were present in men with and without bladder calculi undergoing surgical intervention for benign prostatic hyperplasia induced bladder outlet obstruction. Materials and Methods Men who elected surgery for bladder outlet obstruction secondary to benign prostatic hyperplasia with and without bladder calculi were assessed prospectively and compared. Men without bladder calculi retained more than 150 ml urine post-void residual urine. Medical history, serum electrolytes and 24-hour urinary metabolic studies were compared. Results Of the men 27 had bladder calculi and 30 did not. Bladder calculi were associated with previous renal stone disease in 36.7% of patients (11 of 30) vs 4% (2 of 27) and gout was associated in 13.3% (4 of 30) vs 0% (0 of 27) (p <0.01 and 0.05, respectively). There was no observed difference in the history of other medical conditions or in serum electrolytes. Bladder calculi were associated with lower 24-hour urinary pH (median 5.9 vs 6.4, p = 0.02), lower 24-hour urinary magnesium (median 106 vs 167 mmol, p = 0.01) and increased 24-hour urinary uric acid supersaturation (median 2.2 vs 0.6, p <0.01). Conclusions In this comparative prospective analysis patients with bladder outlet obstruction and benign prostatic hyperplasia with bladder calculi were more likely to have a renal stone disease history, low urinary pH, low urinary magnesium and increased urinary uric acid supersaturation. These findings suggest that, like the pathogenesis of nephrolithiasis, the pathogenesis of bladder calculi is likely complex with multiple contributing lithogenic factors, including metabolic abnormalities and not just urinary stasis. PMID:23159588

Do Maori and Pacific Islander men present with more advanced prostate cancer than European New Zealand men? An analysis of 486 men undergoing biopsy in Auckland.

PubMed

Pokorny, Morgan R; Scott, David J

2011-04-01

• To address the question of whether Maori and Pacific Islander men in Auckland present with more advanced prostate cancer at diagnosis than New Zealand European or European men. • A retrospective database audit was undertaken of all men presenting for a first prostate biopsy under the Auckland Hospital Urology Service in 2005 and 2006. • Ethnicity was coded from self-identification codes on hospital databases. • Population numbers were obtained from the 2006 Census figures from Statistics New Zealand. • Primary outcome measures used as surrogates for advanced disease were PSA level at biopsy, Gleason Score and palpable abnormality on digital rectal examination and rates of metastatic disease as determined by nuclear medicine bone scan. • There was no appreciable difference when Maori and Pacific Islander men were compared with European men for median PSA level (13.30 vs 12.55 ng/mL, P = 0.264); median Gleason score (7 and 7), mean Gleason score (7.0 vs 6.9, P = 0.196) or the proportion of Gleason Score 7 or 8-10 (P = 0.431) • There was no difference between the rates of metastatic disease at presentation (11.5% vs 7.8%, P = 0.376). • There appeared to be a significant difference in the proportion of Maori and Pacific Islanders presenting with palpable disease (67.2%) compared with European men (53.3%, P = 0.042). • The crude population biopsy rate per 100,000 was similar for Maori and Pacific Islander and European men (560 vs 547). • Maori and Pacific Islander men present with similar prostate cancer characteristics to European men at diagnosis but there appears to be a real discrepancy in the rates of palpable disease. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

Detection of Local, Regional, and Distant Recurrence in Patients With PSA Relapse After External-Beam Radiotherapy Using {sup 11}C-Choline Positron Emission Tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Breeuwsma, Anthonius J., E-mail: a.j.breeuwsma@uro.umcg.n; Departments of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen; Pruim, Jan

2010-05-01

Purpose: An elevated serum prostate-specific antigen (PSA) level cannot distinguish between local-regional recurrences and the presence of distant metastases after treatment with curative intent for prostate cancer. With the advent of salvage treatment such as cryotherapy, it has become important to localize the site of recurrence (local or distant). In this study, the potential of {sup 11}C-choline positron emission tomography (PET) to identify site of recurrence was investigated in patients with rising PSA after external-beam radiotherapy (EBRT). Methods and Materials: Seventy patients with histologically proven prostate cancer treated with EBRT and showing biochemical recurrence as defined by American Society formore » Therapeutic Radiology and Oncology consensus statement and 10 patients without recurrence underwent a PET scan using 400 MBq {sup 11}C-choline intravenously. Biopsy-proven histology from the site of suspicion, findings with other imaging modalities, clinical follow-up and/or response to adjuvant therapy were used as comparative references. Results: None of the 10 patients without biochemical recurrence had a positive PET scan. Fifty-seven of 70 patients with biochemical recurrence (median PSA 9.1 ng/mL; mean PSA 12.3 ng/mL) showed an abnormal uptake pattern (sensitivity 81%). The site of recurrence was only local in 41 of 57 patients (mean PSA 11.1 ng/mL at scan), locoregionally and/or distant in 16 of 57 patients (mean PSA 17.7 ng/mL). Overall the positive predictive value and negative predictive value for {sup 11}C-choline PET scan were 1.0 and 0.44 respectively. Accuracy was 84%. Conclusions: {sup 11}C-choline PET scan is a sensitive technique to identify the site of recurrence in patients with PSA relapse after EBRT for prostate cancer.« less

Why and Where do We Miss Significant Prostate Cancer with Multi-parametric Magnetic Resonance Imaging followed by Magnetic Resonance-guided and Transrectal Ultrasound-guided Biopsy in Biopsy-naïve Men?

PubMed

Schouten, Martijn G; van der Leest, Marloes; Pokorny, Morgan; Hoogenboom, Martijn; Barentsz, Jelle O; Thompson, Les C; Fütterer, Jurgen J

2017-06-01

Knowledge of significant prostate (sPCa) locations being missed with magnetic resonance (MR)- and transrectal ultrasound (TRUS)-guided biopsy (Bx) may help to improve these techniques. To identify the location of sPCa lesions being missed with MR- and TRUS-Bx. In a referral center, 223 consecutive Bx-naive men with elevated prostate specific antigen level and/or abnormal digital rectal examination were included. Histopathologically-proven cancer locations, Gleason score, and tumor length were determined. All patients underwent multi-parametric MRI and 12-core systematic TRUS-Bx. MR-Bx was performed in all patients with suspicion of PCa on multi-parametric MRI (n=142). Cancer locations were compared between MR- and TRUS-Bx. Proportions were expressed as percentages, and the corresponding 95% confidence intervals were calculated. In total, 191 lesions were found in 108 patients with sPCa. From these lesion 74% (141/191) were defined as sPCa on either MR- or TRUS-Bx. MR-Bx detected 74% (105/141) of these lesions and 61% (86/141) with TRUS-Bx. TRUS-Bx detected more lesions compared with MR-Bx (140 vs 109). However, these lesions were often low risk (39%). Significant lesions missed with MR-Bx most often had involvement of dorsolateral (58%) and apical (37%) segments and missed segments with TRUS-Bx were located anteriorly (79%), anterior midprostate (50%), and anterior apex (23%). Both techniques have difficulties in detecting apical lesions. MR-Bx most often missed cancer with involvement of the dorsolateral part (58%) and TRUS-Bx with involvement of the anterior part (79%). Both biopsy techniques miss cancer in specific locations within the prostate. Identification of these lesions may help to improve these techniques. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

5-Year Downstream Outcomes Following Prostate-Specific Antigen (PSA) Screening in Older Men

PubMed Central

Walter, Louise C.; Fung, Kathy Z.; Kirby, Katharine A.; Shi, Ying; Espaldon, Roxanne; O'Brien, Sarah; Freedland, Stephen J.; Powell, Adam A.; Hoffman, Richard M.

2013-01-01

Background Despite ongoing controversies surrounding PSA screening, large numbers of men age 65+ undergo screening. However, there are few data quantifying the chain of events following screening in clinical practice to better inform decisions. The objective of this study is to quantify 5-year downstream outcomes following a PSA screening result > 4 ng/ml in older men. Methods Longitudinal cohort study of 295,645 men age 65+ who underwent PSA screening in the VA healthcare system in 2003 and were followed for 5 years using national VA and Medicare data. Among men whose index screening PSA was > 4 ng/ml we determined the number who underwent biopsy, were diagnosed with prostate cancer, were treated and survived 5-years, according to baseline characteristics. Biopsy and treatment complications were also assessed. Results 25,208 (8.5%) men had an index PSA > 4 ng/ml. During 5-year follow-up, 8,313 (33%) men underwent at least one biopsy, 5,220 (63%) of men biopsied were diagnosed with prostate cancer of whom 4,284 (82%) were treated. Receipt of biopsy decreased with advancing age and worsening comorbidity (P<0.001), whereas the percentage treated for biopsy-detected cancer exceeded 75% even among men age 85+, those with Charlson score 3+, and those with low-risk cancer. Among men with biopsy-detected cancer, the risk of dying of non-prostate cancer causes increased with advancing age and comorbidity (P<0.001). 468 (6%) of men had 7-day biopsy complications. Treatment complications included 584 (14%) men with new incontinence and 588 (14%) men with new erectile dysfunction. Conclusions Receipt of biopsy is low in older men with abnormal screening PSA and decreases with advancing age and comorbidity. However, once biopsy detects cancer most men undergo immediate treatment regardless of advancing age, comorbidity, or low-risk cancer. Understanding downstream outcomes in clinical practice should better inform individualized decisions among older men considering PSA screening. PMID:23588999

Contribution of 11C-Choline PET/CT in prostate carcinoma biochemical relapse with serum PSA level below 1 ng/ml.

PubMed

Gómez-de la Fuente, F J; Martínez-Rodríguez, I; de Arcocha-Torres, M; Quirce, R; Jiménez-Bonilla, J; Martínez-Amador, N; Banzo, I

11 C-choline PET/CT has demonstrated good results in the restaging of prostate cancer (PCa) with high serum prostate specific antigen (PSA), but its use in patients with low serum PSA is controversial. Our aim was to evaluate the contribution of 11 C-choline PET/CT in patients with PCa, biochemical relapse and PSA <1 ng/ml. Fifty consecutive patients (mean age: 65.9±5.6 years) with biochemical relapse of PCa and serum PSA <1ng/ml were evaluated retrospectively. PET/CT was performed 20min after intravenous administration of 555-740 MBq of 11 C-choline. Minimum follow up time was 30 months. Twenty-one out of 50 patients (42%) had an abnormal 11 C-choline PET/CT. In 7 out of 21 patients (14%) tumor was confirmed (4 in prostatic bed, 4 in pelvic lymph nodes, 2 in mediastinal lymph nodes and one synchronous sigmoid carcinoma), and in all cases the initial therapeutic planning was modified. In 2 patients (4%) subsequent tests diagnosed a benign disease (one sarcoidosis, one tuberculosis sequelae) and in 3 patients (6%) they ruled out pathology. The other 9 patients (18%) had no further assessment (7 mediastinal and 4 pelvic lymph nodes). Twenty-nine out of 50 patients (58%) had a normal PET/CT. At 30 months, follow up recurrence was confirmed only in 2 of these patients. 11 C-choline PET/CT proved its usefulness in demonstrating tumor in 14% of patients with BR of PCa and serum PSA <1ng/ml, with therapeutic implications. In 4% of patients a benign condition was detected. A normal 11 C-choline PET/CT was associated with a very low rate of recurrence at 30 months. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

A hybrid strategy of offline adaptive planning and online image guidance for prostate cancer radiotherapy.

PubMed

Lei, Yu; Wu, Qiuwen

2010-04-21

Offline adaptive radiotherapy (ART) has been used to effectively correct and compensate for prostate motion and reduce the required margin. The efficacy depends on the characteristics of the patient setup error and interfraction motion through the whole treatment; specifically, systematic errors are corrected and random errors are compensated for through the margins. In online image-guided radiation therapy (IGRT) of prostate cancer, the translational setup error and inter-fractional prostate motion are corrected through pre-treatment imaging and couch correction at each fraction. However, the rotation and deformation of the target are not corrected and only accounted for with margins in treatment planning. The purpose of this study was to investigate whether the offline ART strategy is necessary for an online IGRT protocol and to evaluate the benefit of the hybrid strategy. First, to investigate the rationale of the hybrid strategy, 592 cone-beam-computed tomography (CBCT) images taken before and after each fraction for an online IGRT protocol from 16 patients were analyzed. Specifically, the characteristics of prostate rotation were analyzed. It was found that there exist systematic inter-fractional prostate rotations, and they are patient specific. These rotations, if not corrected, are persistent through the treatment fraction, and rotations detected in early fractions are representative of those in later fractions. These findings suggest that the offline adaptive replanning strategy is beneficial to the online IGRT protocol with further margin reductions. Second, to quantitatively evaluate the benefit of the hybrid strategy, 412 repeated helical CT scans from 25 patients during the course of treatment were included in the replanning study. Both low-risk patients (LRP, clinical target volume, CTV = prostate) and intermediate-risk patients (IRP, CTV = prostate + seminal vesicles) were included in the simulation. The contours of prostate and seminal vesicles were delineated on each CT. The benefit of margin reduction to compensate for both rotation and deformation in the hybrid strategy was evaluated geometrically. With the hybrid strategy, the planning margins can be reduced by 1.4 mm for LRP, and 2.0 mm for IRP, compared with the standard online IGRT only, to maintain the same 99% target volume coverage. The average relative reduction in planning target volume (PTV) based on the internal target volume (ITV) from PTV based on CTV is 19% for LRP, and 27% for IRP.

Assessing cardiac physical examination skills using simulation technology and real patients: a comparison study.

PubMed

Hatala, Rose; Issenberg, S Barry; Kassen, Barry; Cole, Gary; Bacchus, C Maria; Scalese, Ross J

2008-06-01

High-stakes assessments of doctors' physical examination skills often employ standardised patients (SPs) who lack physical abnormalities. Simulation technology provides additional opportunities to assess these skills by mimicking physical abnormalities. The current study examined the relationship between internists' cardiac physical examination competence as assessed with simulation technology compared with that assessed with real patients (RPs). The cardiac physical examination skills and bedside diagnostic accuracy of 28 internists were assessed during an objective structured clinical examination (OSCE). The OSCE included 3 modalities of cardiac patients: RPs with cardiac abnormalities; SPs combined with computer-based, audio-video simulations of auscultatory abnormalities, and a cardiac patient simulator (CPS) manikin. Four cardiac diagnoses and their associated cardiac findings were matched across modalities. At each station, 2 examiners independently rated a participant's physical examination technique and global clinical competence. Two investigators separately scored diagnostic accuracy. Inter-rater reliability between examiners for global ratings (GRs) ranged from 0.75-0.78 for the different modalities. Although there was no significant difference between participants' mean GRs for each modality, the correlations between participants' performances on each modality were low to modest: RP versus SP, r = 0.19; RP versus CPS, r = 0.22; SP versus CPS, r = 0.57 (P < 0.01). Methodological limitations included variability between modalities in the components contributing to examiners' GRs, a paucity of objective outcome measures and restricted case sampling. No modality provided a clear 'gold standard' for the assessment of cardiac physical examination competence. These limitations need to be addressed before determining the optimal patient modality for high-stakes assessment purposes.

Effectiveness of stress management in patients undergoing transrectal ultrasound-guided biopsy of the prostate.

PubMed

Chiu, Li-Pin; Tung, Heng-Hsin; Lin, Kuan-Chia; Lai, Yu-Wei; Chiu, Yi-Chun; Chen, Saint Shiou-Sheng; Chiu, Allen W

2016-01-01

To assess the utilization of stress management in relieving anxiety and pain among patients who undergo transrectal ultrasound (TRUS)-guided biopsy of the prostate. Eighty-two patients admitted to a community hospital for a TRUS biopsy of the prostate participated in this case-controlled study. They were divided into an experimental group that was provided with stress management and a control group that received only routine nursing care. Stress management included music therapy and one-on-one simulation education. Before and after the TRUS biopsy, the patients' state-anxiety inventory score, pain visual analogue scale (VAS), respiratory rate, heart rate, and blood pressure were obtained. There were no differences in baseline and disease characteristics between the two groups. The VAS in both groups increased after the TRUS biopsy, but the difference in pre- and postbiopsy VAS scores was significantly lower in the experimental group (P=0.03). Patients in both groups experienced mild anxiety before and after the biopsy, but those in the experimental group displayed a significantly greater decrease in postbiopsy state-anxiety inventory score compared to the control group (P=0.02). Stress management can alleviate anxiety and pain in patients who received a TRUS biopsy of the prostate under local anesthesia.

On complexity and homogeneity measures in predicting biological aggressiveness of prostate cancer; Implication of the cellular automata model of tumor growth.

PubMed

Tanase, Mihai; Waliszewski, Przemyslaw

2015-12-01

We propose a novel approach for the quantitative evaluation of aggressiveness in prostate carcinomas. The spatial distribution of cancer cell nuclei was characterized by the global spatial fractal dimensions D0, D1, and D2. Two hundred eighteen prostate carcinomas were stratified into the classes of equivalence using results of ROC analysis. A simulation of the cellular automata mix defined a theoretical frame for a specific geometric representation of the cell nuclei distribution called a local structure correlation diagram (LSCD). The LSCD and dispersion Hd were computed for each carcinoma. Data mining generated some quantitative criteria describing tumor aggressiveness. Alterations in tumor architecture along progression were associated with some changes in both shape and the quantitative characteristics of the LSCD consistent with those in the automata mix model. Low-grade prostate carcinomas with low complexity and very low biological aggressiveness are defined by the condition D0 < 1.545 and Hd < 38. High-grade carcinomas with high complexity and very high biological aggressiveness are defined by the condition D0 > 1.764 and Hd < 38. The novel homogeneity measure Hd identifies carcinomas with very low aggressiveness within the class of complexity C1 or carcinomas with very high aggressiveness in the class C7. © 2015 Wiley Periodicals, Inc.

A fully nonparametric estimator of the marginal survival function based on case–control clustered age-at-onset data

PubMed Central

Gorfine, Malka; Bordo, Nadia; Hsu, Li

2017-01-01

Summary Consider a popular case–control family study where individuals with a disease under study (case probands) and individuals who do not have the disease (control probands) are randomly sampled from a well-defined population. Possibly right-censored age at onset and disease status are observed for both probands and their relatives. For example, case probands are men diagnosed with prostate cancer, control probands are men free of prostate cancer, and the prostate cancer history of the fathers of the probands is also collected. Inherited genetic susceptibility, shared environment, and common behavior lead to correlation among the outcomes within a family. In this article, a novel nonparametric estimator of the marginal survival function is provided. The estimator is defined in the presence of intra-cluster dependence, and is based on consistent smoothed kernel estimators of conditional survival functions. By simulation, it is shown that the proposed estimator performs very well in terms of bias. The utility of the estimator is illustrated by the analysis of case–control family data of early onset prostate cancer. To our knowledge, this is the first article that provides a fully nonparametric marginal survival estimator based on case–control clustered age-at-onset data. PMID:27436674

An animal model to study lower urinary tract symptoms and erectile dysfunction: the hyperlipidaemic rat.

PubMed

Rahman, Nadeem U; Phonsombat, Surat; Bochinski, Derek; Carrion, Rafael E; Nunes, Lora; Lue, Tom F

2007-09-01

To present evidence that rats fed a high-fat diet could serve as a useful animal model to study both lower urinary tract symptoms (LUTS) and erectile dysfunction (ED), as recent epidemiological studies have shown a strong association between LUTS and ED but the physiological basis behind this relationship is unknown. In all, 24 male Sprague-Dawley rats were divided into two groups: nine controls were fed a 'normal' diet and 15 were fed a high-fat diet (hyperlipidaemic rats). After 6 months all the rats had bladder and erectile functions evaluated using awake cystometry and cavernosal nerve electrostimulation, respectively. After the functional studies were completed, the penis, prostate and bladder were collected for immunohistochemical analysis. The hyperlipidaemic rats had significantly higher serum cholesterol and low-density lipoprotein than the controls (P < 0.05). The hyperlipidaemic rats also had significantly worse erectile function (P = 0.004) and developed more bladder overactivity (P = 0.004) than the controls. In the hyperlipidaemic rats there was significant muscle hypertrophy in the peri-urethral lobe of the prostate (P < 0.001) and in the bladder (P < 0.05). There was also greater P2X(1) (purinoceptor) staining as well as other molecular changes in the bladder of the hyperlipidaemic rats. In this hyperlipidaemic rat model three abnormalities were consistently detected: prostatic enlargement, bladder overactivity, and ED. This rat model could be a useful research tool for understanding the common causes of LUTS and ED, as well as facilitating the development of preventive measures and better therapies to treat both conditions.

Bicalutamide-induced hepatotoxicity: A rare adverse effect.

PubMed

Hussain, Salwa; Haidar, Abdallah; Bloom, Robert E; Zayouna, Nafea; Piper, Michael H; Jafri, Syed-Mohammed R

2014-01-01

Male, 81 FINAL DIAGNOSIS: Prostate cancer Symptoms: Anorexia • dark urine • joundice • letargy Casodex Clinical Procedure: - Specialty: Oncology. Adverse events of drug therapy. Bicalutamide is a nonsteroidal anti-androgen used extensively during the initiation of androgen deprivation therapy with a luteinizing hormone-releasing hormone (LHRH) agonist to reduce the symptoms of tumor flare in patients with metastatic prostate neoplasm. It can cause gynecomastia, hot flashes, fatigue, and decreased libido through competitive androgen receptor blockade. Although not as common, acute drug-induced liver injury is also possible with bicalutamide therapy. Typically, this results in transient derangement of liver function and patients remain asymptomatic. We share our experience with a case of symptomatic acute hepatotoxicity secondary to the use of bicalutamide and use this opportunity to present a brief review of existing literature. An 81-year-old African American male with metastatic prostate neoplasm presented with nonspecific symptoms along with jaundice of 1-day duration. He was started on a trial of bicalutamide 3 weeks prior to presentation. On physical examination, scleral icterus was noted. Workup revealed acutely elevated liver transaminases (>5 times the upper limit of normal), alkaline phosphatase, conjugated hyperbilirubinemia, and coagulopathy. Other etiologies, including viruses, common toxins, drugs, autoimmune, and copper-induced hepatitis, were considered. Bicalutamide was discontinued and the patient was managed with supportive care. He showed improvement of clinical and laboratory abnormalities within days. While rare, clinically significant and potentially life-threatening liver injury can result from use of bicalutamide. Prompt recognition and discontinuation of bicalutamide is necessary to avoid serious complications from this adverse reaction.

A Review of the Surgical Management of Perineal Hernias in Dogs.

PubMed

Gill, Sukhjit Singh; Barstad, Robert D

2018-05-14

Perineal hernia refers to the failure of the muscular pelvic diaphragm to support the rectal wall, resulting in herniation of pelvic and, occasionally, abdominal viscera into the subcutaneous perineal region. The proposed causes of pelvic diaphragm weakness include tenesmus associated with chronic prostatic disease or constipation, myopathy, rectal abnormalities, and gonadal hormonal imbalances. The most common presentation of perineal hernia in dogs is a unilateral or bilateral nonpainful swelling of the perineum. Clinical signs do occur, but not always. Clinical signs may include constipation, obstipation, dyschezia, tenesmus, rectal prolapse, stranguria, or anuria. The definitive diagnosis of perineal hernia is based on clinical signs and findings of weak pelvic diaphragm musculature during a digital rectal examination. In dogs, perineal hernias are mostly treated by surgical intervention. Appositional herniorrhaphy is sometimes difficult to perform as the levator ani and coccygeus muscles are atrophied and unsuitable for use. Internal obturator muscle transposition is the most commonly used technique. Additional techniques include superficial gluteal and semitendinosus muscle transposition, in addition to the use of synthetic implants and biomaterials. Pexy techniques may be used to prevent rectal prolapse and bladder and prostate gland displacement. Postoperative care involves analgesics, antibiotics, a low-residue diet, and stool softeners.

Prostate cancer, comorbidity, and participation in randomized controlled trials of therapy.

PubMed

Chao, Herta H; Mayer, Tina; Concato, John; Rose, Michal G; Uchio, Edward; Kelly, Wm Kevin

2010-03-01

Randomized controlled trials (RCTs) evaluate the potential benefits of chemotherapy regimens and guide clinical care for patients with cancer. Inclusion criteria for RCTs are usually stringent and may exclude many patients seen in clinical practice. Our objective was to determine the proportion of men with castrate-resistant prostate cancer (CRPC) in a clinical setting that would have been excluded from major phase 3 RCTs. We reviewed eligibility criteria from 24 phase 3 clinical trials evaluating chemotherapy for CRPC active from January, 2004, through April, 2008. We created a common list of criteria used in at least 3 studies and separately considered the criteria from a prominent RCT (TAX 327). We applied these criteria to a population of patients with CRPC treated during 2004 to 2006 at the Veterans Affairs Connecticut Healthcare System. Among 106 patients with CRPC, 99 (93%) had complete medical records, and 45 (45%) of the 99 would have been excluded from RCTs. Common reasons for exclusion were abnormal laboratory values, other malignancies, and other serious medical conditions including cardiac disease. Almost half of the CRPC patients examined in a clinical setting would have been ineligible for phase 3 RCTs, highlighting that such trials may not be applicable to general oncology practice.

Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer

PubMed Central

Dal Pra, Alan; Locke, Jennifer A.; Borst, Gerben; Supiot, Stephane; Bristow, Robert G.

2016-01-01

Radiation therapy (RT) is one of the mainstay treatments for prostate cancer (PCa). The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: (1) androgen signaling pathway; (2) hypoxic tumor cells and regions; (3) DNA damage response (DDR) pathway; and (4) abnormal extra-/intracell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa. PMID:26909338

The Relationship of Comorbidities and Patient Navigation to Time to Diagnostic Resolution after Abnormal Cancer Screening

PubMed Central

Whitley, Elizabeth M; Raich, Peter C; Dudley, Donald J; Freund, Karen M; Paskett, Electra D; Patierno, Steven R; Simon, Melissa; Warren-Mears, Victoria; Snyder, Frederick R

2016-01-01

Background Whether patient navigation improves outcomes in patients with comorbidities is unknown. Study aims were to determine the effect of comorbidities on time to diagnostic resolution following an abnormal cancer screening test, and to examine for patients with comorbidities, if patient navigation improves timeliness and likelihood of diagnostic resolution compared to patients without navigation. Methods A secondary analysis from the Patient Navigation Research Program sites that collected comorbidity data using the Charlson Comorbidity Index (CCI) was conducted. Participants were 6,349 patients with abnormal breast, cervical, colon or prostate cancer screening tests between 2007 and 2011. The intervention was patient navigation or usual care. CCI data were highly skewed across projects and cancer sites and were categorized as 0, no comorbidities identified, CCI score of 0 (76% of cases); 1, CCI score of 1 (16% of cases); or 2, CCI score of ≥2 (8% of cases). A separate adjusted hazards ratio for each site and cancer type was obtained, and then pooled using meta-analysis random effects methodology. Results Having a CCI score of ≥2 delayed the time to diagnostic resolution following an abnormal cancer screening test compared with those with fewer than one comorbidity. Patient Navigation reduced delays in diagnostic resolution with the greatest benefit seen in those with a CCI score of ≥2. Conclusions Persons with a CCI score of ≥2 experienced significant delays in timely diagnostic care compared to patients without comorbidities. Patient navigation was effective in reducing delays in diagnostic resolution among those with CCI scores > 1. PMID:27648520

Scintillating fiber optic dosimeters for breast and prostate brachytherapy

NASA Astrophysics Data System (ADS)

Moutinho, L. M.; Castro, I. F.; Freitas, H.; Melo, J.; Silva, P.; Gonçalves, A.; Peralta, L.; Rachinhas, P. J.; Simões, P. C. P. S.; Pinto, S.; Pereira, A.; Santos, J. A. M.; Costa, M.; Veloso, J. F. C. A.

2017-02-01

Brachytherapy is a radiotherapy modality where the radioactive material is placed close to the tumor, being a common treatment for skin, breast, gynecological and prostate cancers. These treatments can be of low-dose-rate, using isotopes with mean energy of 30 keV, or high-dose-rate, using isotopes such as 192Ir with a mean energy of 380 keV. Currently these treatments are performed in most cases without in-vivo dosimetry for quality control and quality assurance. We developed a dosimeter using small diameter probes that can be inserted into the patient's body using standard brachytherapy needles. By performing real-time dosimetry in breast and prostate brachytherapy it will be possible to perform real-time dose correction when deviations from the treatment plan are observed. The dosimeter presented in this work was evaluated in-vitro. The studies consisted in the characterization of the dosimeter with 500 μm diameter sensitive probes (with a BCF-12 scintillating optical fiber) using an inhouse made gelatin breast phantom with a volume of 566 cm3. A breast brachytherapy treatment was simulated considering a tumor volume of 27 cm3 and a prescribed absolute dose of 5 Gy. The dose distribution was determined by the Inverse Planning Simulated Annealing (IPSA) optimization algorithm (ELEKTA). The dwell times estimated from the experimental measurements are in agreement with the prescribed dwell times, with relative error below 3%. The measured signal-to-noise ratio (SNR) including the stem-effect contribution is below 3%.

A computerized tutor prototype for prostate cryotherapy: key building blocks and system evaluation

NASA Astrophysics Data System (ADS)

Rabin, Yoed; Shimada, Kenji; Joshi, Purva; Sehrawat, Anjali; Keelan, Robert; Wilfong, Dona M.; McCormick, James T.

2017-02-01

This paper focuses on the evaluation of a prototype for a computer-based tutoring system for prostate cryosurgery, while reviewing its key building blocks and their benchmark performance. The tutoring system lists geometrical constraints of cryoprobe placement, displays a rendered shape of the prostate, simulates cryoprobe insertion, enables distance measurements, simulates the corresponding thermal history, and evaluates the mismatch between the target region shape and a pre-selected planning isotherm. The quality of trainee planning is measured in comparison with a computergenerated plan, created for each case study by a previously developed planning algorithm, known as bubble-packing. While the tutoring level in this study aims only at geometrical constraints on cryoprobe placement and the resulting thermal history, it creates a unique opportunity to gain insight into the process outside of the operation room. System validation of the tutor has been performed by collecting training data from surgical residents, having no prior experience or advanced knowledge of cryotherapy. Furthermore, the system has been evaluated by graduate engineering students having no formal education in medicine. In terms of match between a planning isotherm and the target region shape, results demonstrate medical residents' performance improved from 4.4% in a pretest to 37.8% in a posttest over a course of 50 minutes of training (within 10% margins from a computer-optimized plan). Comparing those results with the performance of engineering students indicates similar results, suggesting that planning of the cryoprobe layout essentially revolves around geometric considerations.

An accurate method to quantify breathing-induced prostate motion for patients implanted with electromagnetic transponders.

PubMed

Giandini, Tommaso; Panaino, Costanza M V; Avuzzi, Barbara; Morlino, Sara; Villa, Sergio; Bedini, Nice; Carabelli, Gabriele; Frasca, Sarah C; Romanyukha, Anna; Rosenfeld, Anatoly; Pignoli, Emanuele; Valdagni, Riccardo; Carrara, Mauro

2017-03-24

To validate and apply a method for the quantification of breathing-induced prostate motion (BIPM) for patients treated with radiotherapy and implanted with electromagnetic transponders for prostate localization and tracking. For the analysis of electromagnetic transponder signal, dedicated software was developed and validated with a programmable breathing simulator phantom. The software was then applied to 1,132 radiotherapy fractions of 30 patients treated in supine position, and to a further 61 fractions of 2 patients treated in prone position. Application of the software in phantom demonstrated reliability of the developed method in determining simulated breathing frequencies and amplitudes. For supine patients, the in vivo analysis of BIPM resulted in median (maximum) amplitudes of 0.10 mm (0.35 mm), 0.24 mm (0.66 mm), and 0.17 mm (0.61 mm) in the left-right (LR), cranio-caudal (CC), and anterior-posterior (AP) directions, respectively. Breathing frequency ranged between 7.73 and 29.43 breaths per minute. For prone patients, the ranges of the BIPM amplitudes were 0.1-0.5 mm, 0.5-1.3 mm, and 0.7-1.7 mm in the LR, CC, and AP directions, respectively. The developed method was able to detect the BIPM with sub-millimeter accuracy. While for patients treated in supine position the BIPM represents a reduced source of treatment uncertainty, for patients treated in prone position, it can be higher than 3 mm.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meyer, Jeff, E-mail: jmeye3@utsouthwestern.ed; Bluett, Jaques; Amos, Richard

Purpose: Conventional proton therapy with passively scattered beams is used to treat a number of tumor sites, including prostate cancer. Spot scanning proton therapy is a treatment delivery means that improves conformal coverage of the clinical target volume (CTV). Placement of individual spots within a target is dependent on traversed tissue density. Errors in patient alignment perturb dose distributions. Moreover, there is a need for a rational planning approach that can mitigate the dosimetric effect of random alignment errors. We propose a treatment planning approach and then analyze the consequences of various simulated alignment errors on prostate treatments. Methods andmore » Materials: Ten control patients with localized prostate cancer underwent treatment planning for spot scanning proton therapy. After delineation of the clinical target volume, a scanning target volume (STV) was created to guide dose coverage. Errors in patient alignment in two axes (rotational and yaw) as well as translational errors in the anteroposterior direction were then simulated, and dose to the CTV and normal tissues were reanalyzed. Results: Coverage of the CTV remained high even in the setting of extreme rotational and yaw misalignments. Changes in the rectum and bladder V45 and V70 were similarly minimal, except in the case of translational errors, where, as a result of opposed lateral beam arrangements, much larger dosimetric perturbations were observed. Conclusions: The concept of the STV as applied to spot scanning radiation therapy and as presented in this report leads to robust coverage of the CTV even in the setting of extreme patient misalignments.« less

14 CFR 121.915 - Continuing qualification curriculum.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., flight training device, flight simulator, or other equipment, as appropriate, on normal, abnormal, and... training in the type flight training device or the type flight simulator, as appropriate, regarding... flight simulators or flight training devices: Training in operational flight procedures and maneuvers...

14 CFR 121.915 - Continuing qualification curriculum.

Code of Federal Regulations, 2013 CFR

2013-01-01

..., flight training device, flight simulator, or other equipment, as appropriate, on normal, abnormal, and... training in the type flight training device or the type flight simulator, as appropriate, regarding... flight simulators or flight training devices: Training in operational flight procedures and maneuvers...

14 CFR 121.915 - Continuing qualification curriculum.

Code of Federal Regulations, 2012 CFR

2012-01-01

..., flight training device, flight simulator, or other equipment, as appropriate, on normal, abnormal, and... training in the type flight training device or the type flight simulator, as appropriate, regarding... flight simulators or flight training devices: Training in operational flight procedures and maneuvers...

Simulation optimization of PSA-threshold based prostate cancer screening policies

PubMed Central

Zhang, Jingyu; Denton, Brian T.; Shah, Nilay D.; Inman, Brant A.

2013-01-01

We describe a simulation optimization method to design PSA screening policies based on expected quality adjusted life years (QALYs). Our method integrates a simulation model in a genetic algorithm which uses a probabilistic method for selection of the best policy. We present computational results about the efficiency of our algorithm. The best policy generated by our algorithm is compared to previously recommended screening policies. Using the policies determined by our model, we present evidence that patients should be screened more aggressively but for a shorter length of time than previously published guidelines recommend. PMID:22302420

Monitoring Detrusor Oxygenation and Hemodynamics Noninvasively during Dysfunctional Voiding

PubMed Central

Macnab, Andrew J.; Stothers, Lynn S.; Shadgan, Babak

2012-01-01

The current literature indicates that lower urinary tract symptoms (LUTSs) related to benign prostatic hyperplasia (BPH) have a heterogeneous pathophysiology. Pressure flow studies (UDSs) remain the gold standard evaluation methodology for such patients. However, as the function of the detrusor muscle depends on its vasculature and perfusion, the underlying causes of LUTS likely include abnormalities of detrusor oxygenation and hemodynamics, and available treatment options include agents thought to act on the detrusor smooth muscle and/or vasculature. Hence, near infrared spectroscopy (NIRS), an established optical methodology for monitoring changes in tissue oxygenation and hemodynamics, has relevance as a means of expanding knowledge related to the pathophysiology of BPH and potential treatment options. This methodological report describes how to conduct simultaneous NIRS monitoring of detrusor oxygenation and hemodynamics during UDS, outlines the clinical implications and practical applications of NIRS, explains the principles of physiologic interpretation of NIRS voiding data, and proposes an exploratory hypothesis that the pathophysiological causes underlying LUTS include detrusor dysfunction due to an abnormal hemodynamic response or the onset of oxygen debt during voiding. PMID:23019422

Environmental factors, epigenetics, and developmental origin of reproductive disorders.

PubMed

Ho, Shuk-Mei; Cheong, Ana; Adgent, Margaret A; Veevers, Jennifer; Suen, Alisa A; Tam, Neville N C; Leung, Yuet-Kin; Jefferson, Wendy N; Williams, Carmen J

2017-03-01

Sex-specific differentiation, development, and function of the reproductive system are largely dependent on steroid hormones. For this reason, developmental exposure to estrogenic and anti-androgenic endocrine disrupting chemicals (EDCs) is associated with reproductive dysfunction in adulthood. Human data in support of "Developmental Origins of Health and Disease" (DOHaD) comes from multigenerational studies on offspring of diethylstilbestrol-exposed mothers/grandmothers. Animal data indicate that ovarian reserve, female cycling, adult uterine abnormalities, sperm quality, prostate disease, and mating behavior are susceptible to DOHaD effects induced by EDCs such as bisphenol A, genistein, diethylstilbestrol, p,p'-dichlorodiphenyl-dichloroethylene, phthalates, and polyaromatic hydrocarbons. Mechanisms underlying these EDC effects include direct mimicry of sex steroids or morphogens and interference with epigenomic sculpting during cell and tissue differentiation. Exposure to EDCs is associated with abnormal DNA methylation and other epigenetic modifications, as well as altered expression of genes important for development and function of reproductive tissues. Here we review the literature exploring the connections between developmental exposure to EDCs and adult reproductive dysfunction, and the mechanisms underlying these effects. Copyright © 2016 Elsevier Inc. All rights reserved.

Environmental Factors, Epigenetics, and Developmental Origin of Reproductive Disorders

PubMed Central

Ho, Shuk-Mei; Cheong, Ana; Adgent, Margaret A.; Veevers, Jennifer; Suen, Alisa A.; Tam, Neville N.C.; Leung, Yuet-Kin; Jefferson, Wendy N.; Williams, Carmen J.

2016-01-01

Sex-specific differentiation, development, and function of the reproductive system are largely dependent on steroid hormones. For this reason, developmental exposure to estrogenic and anti-androgenic endocrine disrupting chemicals (EDCs) is associated with reproductive dysfunction in adulthood. Human data in support of “Developmental Origins of Health and Disease” (DOHaD) comes from multigenerational studies on offspring of diethylstilbestrol-exposed mothers/grandmothers. Animal data indicate that ovarian reserve, female cycling, adult uterine abnormalities, sperm quality, prostate disease, and mating behavior are susceptible to DOHaD effects induced by EDCs such as bisphenol A, genistein, diethylstilbestrol, p,p′-dichlorodiphenyl-dichloroethylene, phthalates, and polyaromatic hydrocarbons. Mechanisms underlying these EDC effects include direct mimicry of sex steroids or morphogens and interference with epigenomic sculpting during cell and tissue differentiation. Exposure to EDCs is associated with abnormal DNA methylation and other epigenetic modifications, as well as altered expression of genes important for development and function of reproductive tissues. Here we review the literature exploring the connections between developmental exposure to EDCs and adult reproductive dysfunction, and the mechanisms underlying these effects. PMID:27421580

Modeling the impact of prostate edema on LDR brachytherapy: a Monte Carlo dosimetry study based on a 3D biphasic finite element biomechanical model

NASA Astrophysics Data System (ADS)

Mountris, K. A.; Bert, J.; Noailly, J.; Rodriguez Aguilera, A.; Valeri, A.; Pradier, O.; Schick, U.; Promayon, E.; Gonzalez Ballester, M. A.; Troccaz, J.; Visvikis, D.

2017-03-01

Prostate volume changes due to edema occurrence during transperineal permanent brachytherapy should be taken under consideration to ensure optimal dose delivery. Available edema models, based on prostate volume observations, face several limitations. Therefore, patient-specific models need to be developed to accurately account for the impact of edema. In this study we present a biomechanical model developed to reproduce edema resolution patterns documented in the literature. Using the biphasic mixture theory and finite element analysis, the proposed model takes into consideration the mechanical properties of the pubic area tissues in the evolution of prostate edema. The model’s computed deformations are incorporated in a Monte Carlo simulation to investigate their effect on post-operative dosimetry. The comparison of Day1 and Day30 dosimetry results demonstrates the capability of the proposed model for patient-specific dosimetry improvements, considering the edema dynamics. The proposed model shows excellent ability to reproduce previously described edema resolution patterns and was validated based on previous findings. According to our results, for a prostate volume increase of 10-20% the Day30 urethra D10 dose metric is higher by 4.2%-10.5% compared to the Day1 value. The introduction of the edema dynamics in Day30 dosimetry shows a significant global dose overestimation identified on the conventional static Day30 dosimetry. In conclusion, the proposed edema biomechanical model can improve the treatment planning of transperineal permanent brachytherapy accounting for post-implant dose alterations during the planning procedure.

Label free aggressive prostate cancer identification with ultraviolet photoacoustic spectral analysis (Conference Presentation)

NASA Astrophysics Data System (ADS)

Xu, Guan; Davis, Mandy A.; Siddiqui, Javed; Chao, Wan-yu; Tomlins, Scott A.; Wei, John T.; Wang, Xueding

2017-03-01

Prostate cancer (PCa) is the most commonly diagnosed cancer in American men for the past decades. PCa has a relatively low progression rate but the 5 year survival rate decreases dramatically once the cancer has metastasized. Differentiating aggressive from indolent PCa is critical for improving PCa patient outcomes and preventing metastasis and death. Prostate biopsy is the standard procedure for evaluating the presence and aggressiveness of PCa. The microarchitecture of the biopsied tissues visualized by histology process is evaluated by pathologists and assigned a Gleason score as a quantification of the aggressiveness. In our previous study, we have shown that photoacoustic spectral analysis (PASA) is capable of quantifying the Gleason scores of the H&E stained human prostate tissues. In this study, we attempt to assess the Gleason scores without any staining by taking advantage of the strong optical absorption of nucleic acid at ultraviolet wavelengths. PA signals were generated by wide field illumination at 266 nm and received by a hydrophone with a bandwidth of 0-20 MHz. DU145 prostate cancer cells at the concentrations of 0.8, 0.4, 0.05, 0.025 and 0.0125 million per cm3 simulating those in cancerous and normal tissues were first attempted. The measurements were repeated for 10 times at each concentration. A correlation of 0.86 was observed between the PA signal intensities and the cell concentrations. Human PCa tissues with Gleason score 6, 7 and 8 and normal tissues were assessed. With 11 samples, a correlation of 0.89 was found between the Gleason scores and PASA slopes.

Modeling the impact of prostate edema on LDR brachytherapy: a Monte Carlo dosimetry study based on a 3D biphasic finite element biomechanical model.

PubMed

Mountris, K A; Bert, J; Noailly, J; Aguilera, A Rodriguez; Valeri, A; Pradier, O; Schick, U; Promayon, E; Ballester, M A Gonzalez; Troccaz, J; Visvikis, D

2017-03-21

Prostate volume changes due to edema occurrence during transperineal permanent brachytherapy should be taken under consideration to ensure optimal dose delivery. Available edema models, based on prostate volume observations, face several limitations. Therefore, patient-specific models need to be developed to accurately account for the impact of edema. In this study we present a biomechanical model developed to reproduce edema resolution patterns documented in the literature. Using the biphasic mixture theory and finite element analysis, the proposed model takes into consideration the mechanical properties of the pubic area tissues in the evolution of prostate edema. The model's computed deformations are incorporated in a Monte Carlo simulation to investigate their effect on post-operative dosimetry. The comparison of Day1 and Day30 dosimetry results demonstrates the capability of the proposed model for patient-specific dosimetry improvements, considering the edema dynamics. The proposed model shows excellent ability to reproduce previously described edema resolution patterns and was validated based on previous findings. According to our results, for a prostate volume increase of 10-20% the Day30 urethra D10 dose metric is higher by 4.2%-10.5% compared to the Day1 value. The introduction of the edema dynamics in Day30 dosimetry shows a significant global dose overestimation identified on the conventional static Day30 dosimetry. In conclusion, the proposed edema biomechanical model can improve the treatment planning of transperineal permanent brachytherapy accounting for post-implant dose alterations during the planning procedure.

Dose Escalation to the Dominant Intraprostatic Lesion Defined by Sextant Biopsy in a Permanent Prostate I-125 Implant: A Prospective Comparative Toxicity Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gaudet, Marc; Vigneault, Eric; Aubin, Sylviane

2010-05-01

Purpose: Using real-time intraoperative inverse-planned permanent seed prostate implant (RTIOP/PSI), multiple core biopsy maps, and three-dimensional ultrasound guidance, we planned a boost volume (BV) within the prostate to which hyperdosage was delivered selectively. The aim of this study was to investigate the potential negative effects of such a procedure. Methods and Materials: Patients treated with RTIOP/PSI for localized prostate cancer with topographic biopsy results received an intraprostatic boost (boost group [BG]). They were compared with patients treated with a standard plan (reference group [RG]). Plans were generated using a simulated annealing inverse planning algorithm. Prospectively recorded urinary, rectal, and sexualmore » toxicities and dosimetric parameters were compared between groups. Results: The study included 120 patients treated with boost technique who were compared with 70 patients treated with a standard plan. Boost technique did not significantly change the number of seeds (55.1/RG vs. 53.6/BG). The intraoperative prostate V150 was slightly higher in BG (75.2/RG vs. 77.2/BG, p = 0.039). Urethra V100, urethra D90, and rectal D50 were significantly lower in the BG. No significant differences were seen in acute or late urinary, rectal, or sexual toxicities. Conclusions: Because there were no differences between the groups in acute and late toxicities, we believe that BV can be planned and delivered to the dominant intraprostatic lesion without increasing toxicity. It is too soon to say whether a boost technique will ultimately increase local control.« less

A fully actuated robotic assistant for MRI-guided prostate biopsy and brachytherapy

NASA Astrophysics Data System (ADS)

Li, Gang; Su, Hao; Shang, Weijian; Tokuda, Junichi; Hata, Nobuhiko; Tempany, Clare M.; Fischer, Gregory S.

2013-03-01

Intra-operative medical imaging enables incorporation of human experience and intelligence in a controlled, closed-loop fashion. Magnetic resonance imaging (MRI) is an ideal modality for surgical guidance of diagnostic and therapeutic procedures, with its ability to perform high resolution, real-time, high soft tissue contrast imaging without ionizing radiation. However, for most current image-guided approaches only static pre-operative images are accessible for guidance, which are unable to provide updated information during a surgical procedure. The high magnetic field, electrical interference, and limited access of closed-bore MRI render great challenges to developing robotic systems that can perform inside a diagnostic high-field MRI while obtaining interactively updated MR images. To overcome these limitations, we are developing a piezoelectrically actuated robotic assistant for actuated percutaneous prostate interventions under real-time MRI guidance. Utilizing a modular design, the system enables coherent and straight forward workflow for various percutaneous interventions, including prostate biopsy sampling and brachytherapy seed placement, using various needle driver configurations. The unified workflow compromises: 1) system hardware and software initialization, 2) fiducial frame registration, 3) target selection and motion planning, 4) moving to the target and performing the intervention (e.g. taking a biopsy sample) under live imaging, and 5) visualization and verification. Phantom experiments of prostate biopsy and brachytherapy were executed under MRI-guidance to evaluate the feasibility of the workflow. The robot successfully performed fully actuated biopsy sampling and delivery of simulated brachytherapy seeds under live MR imaging, as well as precise delivery of a prostate brachytherapy seed distribution with an RMS accuracy of 0.98mm.

Automatic CT simulation optimization for radiation therapy: A general strategy.

PubMed

Li, Hua; Yu, Lifeng; Anastasio, Mark A; Chen, Hsin-Chen; Tan, Jun; Gay, Hiram; Michalski, Jeff M; Low, Daniel A; Mutic, Sasa

2014-03-01

In radiation therapy, x-ray computed tomography (CT) simulation protocol specifications should be driven by the treatment planning requirements in lieu of duplicating diagnostic CT screening protocols. The purpose of this study was to develop a general strategy that allows for automatically, prospectively, and objectively determining the optimal patient-specific CT simulation protocols based on radiation-therapy goals, namely, maintenance of contouring quality and integrity while minimizing patient CT simulation dose. The authors proposed a general prediction strategy that provides automatic optimal CT simulation protocol selection as a function of patient size and treatment planning task. The optimal protocol is the one that delivers the minimum dose required to provide a CT simulation scan that yields accurate contours. Accurate treatment plans depend on accurate contours in order to conform the dose to actual tumor and normal organ positions. An image quality index, defined to characterize how simulation scan quality affects contour delineation, was developed and used to benchmark the contouring accuracy and treatment plan quality within the predication strategy. A clinical workflow was developed to select the optimal CT simulation protocols incorporating patient size, target delineation, and radiation dose efficiency. An experimental study using an anthropomorphic pelvis phantom with added-bolus layers was used to demonstrate how the proposed prediction strategy could be implemented and how the optimal CT simulation protocols could be selected for prostate cancer patients based on patient size and treatment planning task. Clinical IMRT prostate treatment plans for seven CT scans with varied image quality indices were separately optimized and compared to verify the trace of target and organ dosimetry coverage. Based on the phantom study, the optimal image quality index for accurate manual prostate contouring was 4.4. The optimal tube potentials for patient sizes of 38, 43, 48, 53, and 58 cm were 120, 140, 140, 140, and 140 kVp, respectively, and the corresponding minimum CTDIvol for achieving the optimal image quality index 4.4 were 9.8, 32.2, 100.9, 241.4, and 274.1 mGy, respectively. For patients with lateral sizes of 43-58 cm, 120-kVp scan protocols yielded up to 165% greater radiation dose relative to 140-kVp protocols, and 140-kVp protocols always yielded a greater image quality index compared to the same dose-level 120-kVp protocols. The trace of target and organ dosimetry coverage and the γ passing rates of seven IMRT dose distribution pairs indicated the feasibility of the proposed image quality index for the predication strategy. A general strategy to predict the optimal CT simulation protocols in a flexible and quantitative way was developed that takes into account patient size, treatment planning task, and radiation dose. The experimental study indicated that the optimal CT simulation protocol and the corresponding radiation dose varied significantly for different patient sizes, contouring accuracy, and radiation treatment planning tasks.

Serum levels of endothelial and neural cell adhesion molecules in prostate cancer.

PubMed

Lynch, D F; Hassen, W; Clements, M A; Schellhammer, P F; Wright, G L

1997-08-01

Tumorigenesis and progression to metastatic disease are accompanied by changes in the expression of cell adhesion molecules (CAMs). Normally expressed CAMs, such as E-cadherin, are lost, while others, i.e., ICAM-1, VCAM-1, NCAM, and E-selectin, are altered and overexpressed in progressive disease and metastases. Abnormal levels of these latter CAMs have been observed in melanoma and carcinomas of the colon and breast, and NCAM is overexpressed in small-cell lung carcinoma (SCLC). The objective of this study was to determine if serum levels of ICAM-1, VCAM-1, NCAM, and E-selectin could differentiate patients with benign prostate hypertrophy (BPH) from those with prostate carcinoma (CaP) and identify prostate cancers with high potential for progression to metastatic disease. Serum levels of these CAMs were determined by ELISA in serum from normal males and females and from patients with BPH and CaP before and after treatment. Sera from patients with breast carcinoma, colon carcinoma, melanoma, and small-cell lung carcinoma were also evaluated, as soluble CAMs have been reported to be elevated in these cancer patients. ICAM-1 levels were elevated in sera from patients with breast carcinoma (P = 0.0004) and melanoma (P = 0.0001). VCAM-1 levels were elevated in sera from patients with colon carcinoma (P = 0.0001). NCAM levels were elevated in the sera of patients with SCLC (P = 0.0001). Normal levels of ICAM-1, E-selectin, and NCAM were found in both BPH and pretreatment CaP patients. Median NCAM levels in hormone-refractive CaP patients were significantly greater than in BPH (P = 0.0005) and CaP patients with pathologically determined organ-confined (P = 0.0014) or nonorgan-confined disease (P = 0.0385). VCAM-1 levels were significantly elevated in both BPH patients (P = 0.0002) and CaP patients (P = 0.0002) when compared with levels for normal age-matched donors. None of the CAMs were found to offer an advantage over prostatic-specific antigen (PSA) for monitoring CaP patients following definitive radiotherapy, radical prostatectomy, or hormonal therapy. The results of this study indicate that serum ICAM-1, VCAM-1, NCAM, and E-selectin are not clinically useful biomarkers for differentiating CaP from BPH, for predicting progression, for identifying metastatic potential, or for monitoring treatment.

Targeted Approach to Overcoming Treatment Resistance in Advanced Prostate Cancer

DTIC Science & Technology

2015-09-01

around 20 uM and plateaus off at an at least 10 % lower cell viability (Fig. 2). We next determined the viability of LnCaP cells in the presence of...elsewhere (Negureanu and Salsbury, 2012). In short, the simulations were four 20ns NPT all-­‐atom simulations based on the human MSH2/6 crystal structure...Washington Biotechniques, the following experiments were performed: PROCEDURES: A. Preparation of Human Cancer Cell Line. 1. Thaw out frozen (liquid

TU-H-CAMPUS-JeP3-05: Adaptive Determination of Needle Sequence HDR Prostate Brachytherapy with Divergent Needle-By-Needle Delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borot de Battisti, M; Maenhout, M; Lagendijk, J J W

Purpose: To develop a new method which adaptively determines the optimal needle insertion sequence for HDR prostate brachytherapy involving divergent needle-by-needle dose delivery by e.g. a robotic device. A needle insertion sequence is calculated at the beginning of the intervention and updated after each needle insertion with feedback on needle positioning errors. Methods: Needle positioning errors and anatomy changes may occur during HDR brachytherapy which can lead to errors in the delivered dose. A novel strategy was developed to calculate and update the needle sequence and the dose plan after each needle insertion with feedback on needle positioning errors. Themore » dose plan optimization was performed by numerical simulations. The proposed needle sequence determination optimizes the final dose distribution based on the dose coverage impact of each needle. This impact is predicted stochastically by needle insertion simulations. HDR procedures were simulated with varying number of needle insertions (4 to 12) using 11 patient MR data-sets with PTV, prostate, urethra, bladder and rectum delineated. Needle positioning errors were modeled by random normally distributed angulation errors (standard deviation of 3 mm at the needle’s tip). The final dose parameters were compared in the situations where the needle with the largest vs. the smallest dose coverage impact was selected at each insertion. Results: Over all scenarios, the percentage of clinically acceptable final dose distribution improved when the needle selected had the largest dose coverage impact (91%) compared to the smallest (88%). The differences were larger for few (4 to 6) needle insertions (maximum difference scenario: 79% vs. 60%). The computation time of the needle sequence optimization was below 60s. Conclusion: A new adaptive needle sequence determination for HDR prostate brachytherapy was developed. Coupled to adaptive planning, the selection of the needle with the largest dose coverage impact increases chances of reaching the clinical constraints. M. Borot de Battisti is funded by Philips Medical Systems Nederland B.V.; M. Moerland is principal investigator on a contract funded by Philips Medical Systems Nederland B.V.; G. Hautvast and D. Binnekamp are fulltime employees of Philips Medical Systems Nederland B.V.« less

Tumor or abnormality identification from magnetic resonance images using statistical region fusion based segmentation.

PubMed

Subudhi, Badri Narayan; Thangaraj, Veerakumar; Sankaralingam, Esakkirajan; Ghosh, Ashish

2016-11-01

In this article, a statistical fusion based segmentation technique is proposed to identify different abnormality in magnetic resonance images (MRI). The proposed scheme follows seed selection, region growing-merging and fusion of multiple image segments. In this process initially, an image is divided into a number of blocks and for each block we compute the phase component of the Fourier transform. The phase component of each block reflects the gray level variation among the block but contains a large correlation among them. Hence a singular value decomposition (SVD) technique is adhered to generate a singular value of each block. Then a thresholding procedure is applied on these singular values to identify edgy and smooth regions and some seed points are selected for segmentation. By considering each seed point we perform a binary segmentation of the complete MRI and hence with all seed points we get an equal number of binary images. A parcel based statistical fusion process is used to fuse all the binary images into multiple segments. Effectiveness of the proposed scheme is tested on identifying different abnormalities: prostatic carcinoma detection, tuberculous granulomas identification and intracranial neoplasm or brain tumor detection. The proposed technique is established by comparing its results against seven state-of-the-art techniques with six performance evaluation measures. Copyright © 2016 Elsevier Inc. All rights reserved.

[Infectious endocarditis due to Gemella morbillorum found by splenic infarction--a case report].

PubMed

Hosaka, Yumiko; Kimura, Takuma; Suzuki, Ryo; Chong, Tonghyo; Shoji, Michi; Aoki, Yasuko

2010-09-01

A 64-year-old man with prostate cancer and bone metastasis admitted for nausea, left abdominal pain showed no abnormal, and fever, abdominal ultrasound or chest X-ray findings. Despite antibiotics, left abdominal pain persisted for several days. Abdominal computed tomography (CT), showed splenic infarction. Transesophageal echocardiography suggested infectious endocarditis (IE) as a possible infarction cause, and roth spots were found on the retina. Gemella morbillorum was detected from blood culture. IE commonly causes Fever of Unknown Origin found by infarction. G. morbillorum, an anaerobic gram-positive, viridans group streptococci, is indigenous to the oropharynx, upper respiratory, urogenital, and gastrointestinal tracts, and is thought to have weak toxicity and pathogenicity in the body.

[Portal vein thrombosis associated with hepatic encephalopathy].

PubMed

Iwatani, Nao; Inatomi, Yuichiro; Yonehara, Toshiro; Fujioka, Shodo; Hashimoto, Yoichiro; Hirano, Teruyuki; Uchino, Makoto

2005-03-01

A 54-year-old man who had been administered chlormadinone acetate 3 months after prostatectomy for prostate cancer, acutely developed disorientation and memory disturbance. Six days later, he experienced high grade fever and epigastralgia. He was suspected to have hepatic encephalopathy, because the Fischer ratio was low although serum ammonia level remained normal. Further examinations including abdominal echography and CT scan disclosed a thrombus extending from the portal vein to the superior mesenteric vein together with abnormal collateral vessels originating from the portal vein. He was successfully treated with warfarin potassium, urokinase and heparin sodium. It was suggested that the patient developed hepatic encephalopathy due to portal-systemic circulation shunting secondary to portal vein thrombosis.

Designing image segmentation studies: Statistical power, sample size and reference standard quality.

PubMed

Gibson, Eli; Hu, Yipeng; Huisman, Henkjan J; Barratt, Dean C

2017-12-01

Segmentation algorithms are typically evaluated by comparison to an accepted reference standard. The cost of generating accurate reference standards for medical image segmentation can be substantial. Since the study cost and the likelihood of detecting a clinically meaningful difference in accuracy both depend on the size and on the quality of the study reference standard, balancing these trade-offs supports the efficient use of research resources. In this work, we derive a statistical power calculation that enables researchers to estimate the appropriate sample size to detect clinically meaningful differences in segmentation accuracy (i.e. the proportion of voxels matching the reference standard) between two algorithms. Furthermore, we derive a formula to relate reference standard errors to their effect on the sample sizes of studies using lower-quality (but potentially more affordable and practically available) reference standards. The accuracy of the derived sample size formula was estimated through Monte Carlo simulation, demonstrating, with 95% confidence, a predicted statistical power within 4% of simulated values across a range of model parameters. This corresponds to sample size errors of less than 4 subjects and errors in the detectable accuracy difference less than 0.6%. The applicability of the formula to real-world data was assessed using bootstrap resampling simulations for pairs of algorithms from the PROMISE12 prostate MR segmentation challenge data set. The model predicted the simulated power for the majority of algorithm pairs within 4% for simulated experiments using a high-quality reference standard and within 6% for simulated experiments using a low-quality reference standard. A case study, also based on the PROMISE12 data, illustrates using the formulae to evaluate whether to use a lower-quality reference standard in a prostate segmentation study. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

TH-A-9A-10: Prostate SBRT Delivery with Flattening-Filter-Free Mode: Benefit and Accuracy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, T; Yuan, L; Sheng, Y

Purpose: Flattening-filter-free (FFF) beam mode offered on TrueBeam™ linac enables delivering IMRT at 2400 MU/min dose rate. This study investigates the benefit and delivery accuracy of using high dose rate in the context of prostate SBRT. Methods: 8 prostate SBRT patients were retrospectively studied. In 5 cases treated with 600-MU/min dose rate, continuous prostate motion data acquired during radiation-beam-on was used to analyze motion range. In addition, the initial 1/3 of prostate motion trajectories during each radiation-beam-on was separated to simulate motion range if 2400-MU/min were used. To analyze delivery accuracy in FFF mode, MLC trajectory log files from anmore » additional 3 cases treated at 2400-MU/min were acquired. These log files record MLC expected and actual positions every 20ms, and therefore can be used to reveal delivery accuracy. Results: (1) Benefit. On average treatment at 600-MU/min takes 30s per beam; whereas 2400-MU/min requires only 11s. When shortening delivery time to ~1/3, the prostate motion range was significantly smaller (p<0.001). Largest motion reduction occurred in Sup-Inf direction, from [−3.3mm, 2.1mm] to [−1.7mm, 1.7mm], followed by reduction from [−2.1mm, 2.4mm] to [−1.0mm, 2.4mm] in Ant-Pos direction. No change observed in LR direction [−0.8mm, 0.6mm]. The combined motion amplitude (vector norm) confirms that average motion and ranges are significantly smaller when beam-on was limited to the 1st 1/3 of actual delivery time. (2) Accuracy. Trajectory log file analysis showed excellent delivery accuracy with at 2400 MU/min. Most leaf deviations during beam-on were within 0.07mm (99-percentile). Maximum leaf-opening deviations during each beam-on were all under 0.1mm for all leaves. Dose-rate was maintained at 2400-MU/min during beam-on without dipping. Conclusion: Delivery prostate SBRT with 2400 MU/min is both beneficial and accurate. High dose rates significantly reduced both treatment time and intra-beam prostate motion range. Excellent delivery accuracy was confirmed with very small leaf motion deviation.« less

High-intensity interstitial ultrasound for thermal ablation of focal cancer targets in prostate

NASA Astrophysics Data System (ADS)

Salgaonkar, Vasant A.; Scott, Serena; Kurhanewicz, John; Diederich, Chris J.

2017-03-01

Recent advances in image based techniques such as multi-parametric MRI (MP-MRI) can provide precise targeting of focal disease in the prostate. Thermal ablation of such cancer targets while avoiding rectum, urethra, neurovascular bundles (NVB) and sphincter is clinically challenging. The approach described here employs multi-element ultrasound linear arrays designed for transperineal placement within prostate. They consist of independently powered sectored tubular transducers (6.5 - 8.0 MHz) that provide spatial control of energy deposition in angle and length. Volumetric ablation strategies were investigated through patient-specific biothermal models based on Pennes bioheat transfer equation. The acoustic and heat transfer models used here have been validated in several previous simulation and experimental studies. Focal disease sites in prostate were identified through multi-parametric MR images of representative patient cases (n=3). Focal cancer lesions and critical anatomy (prostate, urethra, rectum, bladder, seminal vesicles) were manually segmented (Mimics, Materialise) and converted to 3D finite element meshes (3-Matic, Materialise). The chosen test cases consisted of patients with medium and large sized glands and models of bulk tissue ablation covered volumes in a single quadrant in posterior prostate, hemi-gland targets and "hockey-stick" targets (lesions in three quadrants). Ultrasound applicator placement was determined such that devices were positioned along the prostate periphery while avoiding surrounding anatomy. Transducer sector angles were chosen based on applicator location within limits of fabrication practicability. Thermal models were numerically solved using finite element methods (FEM) in COMSOL Multiphysics. Temperature and thermal dose distributions were calculated to determine treated volumes (> 240 CEM43C, >52 °C) and safety profiles (<10 CEM43C, <45 °C) for nerve, rectal and urethral sparing. Modeling studies indicated that focal targets could be ablated with single or multiple interstitial applicators placed along the prostate periphery. In the representative cases explored during this study, thermal targets could be ablated with acoustic intensity values between 11 - 19 W/cm2 within 6 - 15 min of sonication time. Unifocal ablation could be performed by a single directional applicator (210° sectors). Hemi-gland targets were ablated by two directional applicators (210° sectors). Hockey-stick ablations were performed using 3 directional applicators (2 - 210° and 1 - 150°).

Comparing photon and proton-based hypofractioned SBRT for prostate cancer accounting for robustness and realistic treatment deliverability.

PubMed

Goddard, Lee C; Brodin, N Patrik; Bodner, William R; Garg, Madhur K; Tomé, Wolfgang A

2018-05-01

To investigate whether photon or proton-based stereotactic body radiation therapy (SBRT is the preferred modality for high dose hypofractionation prostate cancer treatment. Achievable dose distributions were compared when uncertainties in target positioning and range uncertainties were appropriately accounted for. 10 patients with prostate cancer previously treated at our institution (Montefiore Medical Center) with photon SBRT using volumetric modulated arc therapy (VMAT) were identified. MRI images fused to the treatment planning CT allowed for accurate target and organ at risk (OAR) delineation. The clinical target volume was defined as the prostate gland plus the proximal seminal vesicles. Critical OARs include the bladder wall, bowel, femoral heads, neurovascular bundle, penile bulb, rectal wall, urethra and urogenital diaphragm. Photon plan robustness was evaluated by simulating 2 mm isotropic setup variations. Comparative proton SBRT plans employing intensity modulated proton therapy (IMPT) were generated using robust optimization. Plan robustness was evaluated by simulating 2 mm setup variations and 3% or 1% Hounsfield unit (HU) calibration uncertainties. Comparable maximum OAR doses are achievable between photon and proton SBRT, however, robust optimization results in higher maximum doses for proton SBRT. Rectal maximum doses are significantly higher for Robust proton SBRT with 1% HU uncertainty compared to photon SBRT (p = 0.03), whereas maximum doses were comparable for bladder wall (p = 0.43), urethra (p = 0.82) and urogenital diaphragm (p = 0.50). Mean doses to bladder and rectal wall are lower for proton SBRT, but higher for neurovascular bundle, urethra and urogenital diaphragm due to increased lateral scatter. Similar target conformality is achieved, albeit with slightly larger treated volume ratios for proton SBRT, >1.4 compared to 1.2 for photon SBRT. Similar treatment plans can be generated with IMPT compared to VMAT in terms of target coverage, target conformality, and OAR sparing when range and HU uncertainties are neglected. However, when accounting for these uncertainties during robust optimization, VMAT outperforms IMPT in terms of achievable target conformity and OAR sparing. Advances in knowledge: Comparison between achievable dose distributions using modern, robust optimization of IMPT for high dose per fraction SBRT regimens for the prostate has not been previously investigated.

SU-G-201-02: Application of RayStretch in Clinical Cases: A Calculation for Heterogeneity Corrections in LDR Permanent I-125 Prostate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hueso-Gonzalez, F; Vijande, J; Ballester, F

Purpose: Tissue heterogeneities and calcifications have significant impact on the dosimetry of low energy brachytherapy (BT). RayStretch is an analytical algorithm developed in our institution to incorporate heterogeneity corrections in LDR prostate brachytherapy. The aim of this work is to study its application in clinical cases by comparing its predictions with the results obtained with TG-43 and Monte Carlo (MC) simulations. Methods: A clinical implant (71 I-125 seeds, 15 needles) from a real patient was considered. On this patient, different volumes with calcifications were considered. Its properties were evaluated in three ways by i) the Treatment planning system (TPS) (TG-43),more » ii) a MC study using the Penelope2009 code, and iii) RayStretch. To analyse the performance of RayStretch, calcifications located in the prostate lobules covering 11% of the total prostate volume and larger calcifications located in the lobules and underneath the urethra for a total occupied volume of 30% were considered. Three mass densities (1.05, 1.20, and 1.35 g/cm3) were explored for the calcifications. Therefore, 6 different scenarios ranging from small low density calcifications to large high density ones have been discussed. Results: DVH and D90 results given by RayStretch agree within 1% with the full MC simulations. Although no effort has been done to improve RayStretch numerical performance, its present implementation is able to evaluate a clinical implant in a few seconds to the same level of accuracy as a detailed MC calculation. Conclusion: RayStretch is a robust method for heterogeneity corrections in prostate BT supported on TG-43 data. Its compatibility with commercial TPSs and its high calculation speed makes it feasible for use in clinical settings for improving treatment quality. It will allow in a second phase of this project, its use during intraoperative ultrasound planning. This study was partly supported by a fellowship grant from the Spanish Ministry of Education, by the Generalitat Valenciana under Project PROMETEOII/2013/010, by the Spanish Government under Project No. FIS2013-42156 and by the European Commission within the SeventhFramework Program through ENTERVISION (grant agreement number 264552).« less

SU-C-210-02: Impact of Intrafractional Motion On TomoTherapy Stereotactic Body Radiotherapy (SBRT) 4D Dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lian, J; Matney, J; Chao, E

2015-06-15

Purpose: TomoTherapy treatment has unique challenges in handling intrafractional motion compared to conventional LINAC. This study is aimed to gain a realistic and quantitative understanding of motion impact on TomoTherapy SBRT treatment of lung and prostate cancer patients. Methods: A 4D dose engine utilizing GPUs and including motion during treatment was developed for the efficient simulation of TomoTherapy delivered dosimetry. Two clinical CyberKnife lung cases with respiratory motion tracking and two prostate cases with a slower non-periodical organ motion treated by LINAC plus Calypso tracking were used in the study. For each disease site, one selected case has an averagemore » motion (6mm); the other has a large motion (10mm for lung and 15mm for prostate). SBRT of lung and prostate cases were re-planned on TomoTherapy with 12 Gyx4 fractions and 7Gyx5 fractions, respectively, all with 95% PTV coverage. Each case was planned with 4 jaw settings: 1) conventional 1cm static, 2) 2.5cm static, 3) 2.5cm dynamic, and 4) 5cm dynamic. The intrafractional rigid motion of the target was applied in the dose calculation of individual fractions of each plan and total dose was accumulated from multiple fractions. Results: For 1cm static jaw plans with motions applied, PTV coverage is related to motion type and amplitude. For SBRT patients with average motion (6mm), the PTV coverage remains > 95% for lung case and 74% for prostate case. For cases with large motion, PTV coverage drops to 61% for lung SBRT and 49% for prostate SBRT. Plans with other jaws improve uniformity of moving target, but still suffer from poor PTV coverage (< 70%). Conclusion: TomoTherapy lung SBRT is less motion-impacted when average amplitude of respiratory-induced intrafractional motion is present (6mm). When motion is large and/or non-periodic (prostate), all studied plans lead to significantly decreased target coverage in actual delivered dosimetry.« less

A Biodistribution and Toxicity Study of Cobalt Dichloride-N-Acetyl Cysteine in an Implantable MRI Marker for Prostate Cancer Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frank, Steven J., E-mail: sjfrank@mdanderson.org; Johansen, Mary J.; Martirosyan, Karen S.

2013-03-15

Purpose: C4, a cobalt dichloride-N-acetyl cysteine complex, is being developed as a positive-signal magnetic resonance imaging (MRI) marker to localize implanted radioactive seeds in prostate brachytherapy. We evaluated the toxicity and biodistribution of C4 in rats with the goal of simulating the systemic effects of potential leakage from C4 MRI markers within the prostate. Methods and Materials: 9-μL doses (equivalent to leakage from 120 markers in a human) of control solution (0.9% sodium chloride), 1% (proposed for clinical use), and 10% C4 solution were injected into the prostates of male Sprague-Dawley rats via laparotomy. Organ toxicity and cobalt disposition inmore » plasma, tissues, feces, and urine were evaluated. Results: No C4-related morbidity or mortality was observed in the biodistribution arm (60 rats). Biodistribution was measurable after 10% C4 injection: cobalt was cleared rapidly from periprostatic tissue; mean concentrations in prostate were 163 μg/g and 268 μg/g at 5 and 30 minutes but were undetectable by 60 minutes. Expected dual renal-hepatic elimination was observed, with percentages of injected dose recovered in tissues of 39.0 ± 5.6% (liver), >11.8 ± 6.5% (prostate), and >5.3 ± 0.9% (kidney), with low plasma concentrations detected up to 1 hour (1.40 μg/mL at 5-60 minutes). Excretion in urine was 13.1 ± 4.6%, with 3.1 ± 0.54% recovered in feces by 24 hours. In the toxicity arm, 3 animals died in the control group and 1 each in the 1% and 10% groups from surgical or anesthesia-related complications; all others survived to scheduled termination at 14 days. No C4-related adverse clinical signs or organ toxicity were observed. Conclusion: C4-related toxicity was not observed at exposures at least 10-fold the exposure proposed for use in humans. These data demonstrating lack of systemic toxicity with dual routes of elimination in the event of in situ rupture suggest that C4 warrants further investigation as an MRI marker for prostate brachytherapy.« less

Detection of Recurrent Prostate Carcinoma with anti-1-Amino-3-18F-Fluorocyclobutane-1-Carboxylic Acid PET/CT and 111In–Capromab Pendetide SPECT/CT

PubMed Central

Savir-Baruch, Bital; Nieh, Peter T.; Master, Viraj A.; Halkar, Raghuveer K.; Rossi, Peter J.; Lewis, Melinda M.; Nye, Jonathon A.; Yu, Weiping; Bowman, F. DuBois; Goodman, Mark M.

2011-01-01

Purpose: To compare the diagnostic performance of the synthetic amino acid analog radiotracer anti-1-amino-3-fluorine 18-fluorocyclobutane-1-carboxylic acid (anti-3-18F-FACBC) with that of indium 111 (111In)–capromab pendetide in the detection of recurrent prostate carcinoma. Materials and Methods: This prospective study was approved by the institutional review board and complied with HIPAA guidelines. Written informed consent was obtained. Fifty patients (mean age, 68.3 years ± 8.1 [standard deviation]; age range, 50–90 years) were included in the study on the basis of the following criteria: (a) Recurrence of prostate carcinoma was suspected after definitive therapy for localized disease, (b) bone scans were negative, and (c) anti-3-18F-FACBC positron emission tomography (PET)/computed tomography (CT) and 111In–capromab pendetide single photon emission computed tomography (SPECT)/CT were performed within 6 weeks of each other. Studies were evaluated by two experienced interpreters for abnormal uptake suspicious for recurrent disease in the prostate bed and extraprostatic locations. The reference standard was a combination of tissue correlation, imaging, laboratory, and clinical data. Diagnostic performance measures were calculated and tests of the statistical significance of differences determined by using the McNemar χ2 test as well as approximate tests based on the difference between two proportions. Results: For disease detection in the prostate bed, anti-3-18F-FACBC had a sensitivity of 89% (32 of 36 patients; 95% confidence interval [CI]: 74%, 97%), specificity of 67% (eight of 12 patients; 95% CI: 35%, 90%), and accuracy of 83% (40 of 48 patients; 95% CI: 70%, 93%). 111In–capromab pendetide had a sensitivity of 69% (25 of 36 patients; 95% CI: 52%, 84%), specificity of 58% (seven of 12 patients; 95% CI: 28%, 85%), and accuracy of 67% (32 of 48 patients; 95% CI: 52%, 80%). In the detection of extraprostatic recurrence, anti-3-18F-FACBC had a sensitivity of 100% (10 of 10 patients; 95% CI: 69%, 100%), specificity of 100% (seven of seven patients; 95% CI: 59%, 100%), and accuracy of 100% (17 of 17 patients; 95% CI: 80%, 100%). 111In–capromab pendetide had a sensitivity of 10% (one of 10 patients; 95% CI: 0%, 45%), specificity of 100% (seven of seven patients; 95% CI: 59%, 100%), and accuracy of 47% (eight of 17 patients; 95% CI: 23%, 72%). Conclusion: anti-3-18F-FACBC PET/CT was more sensitive than 111In–capromab pendetide SPECT/CT in the detection of recurrent prostate carcinoma and is highly accurate in the differentiation of prostatic from extraprostatic disease. © RSNA, 2011 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11102023/-/DC1 PMID:21493787

Use of Drama Students as "Clients" in Teaching Abnormal Psychology.

ERIC Educational Resources Information Center

Gilliland, Kirby

1982-01-01

Describes the use of drama students to role play subjects of case studies in simulations of standard interviews in a college-level abnormal psychology class. Graduate drama students role-played clients in interviews with instructors or student panels. After the interviews, class discussion covered alternative possible diagnoses and possible…

Hypothesis on Serenoa repens (Bartram) small extract inhibition of prostatic 5α-reductase through an in silico approach on 5β-reductase x-ray structure

PubMed Central

Giachetti, Daniela; Biagi, Marco; Manetti, Fabrizio; De Vico, Luca

2016-01-01

Benign prostatic hyperplasia is a common disease in men aged over 50 years old, with an incidence increasing to more than 80% over the age of 70, that is increasingly going to attract pharmaceutical interest. Within conventional therapies, such as α-adrenoreceptor antagonists and 5α-reductase inhibitor, there is a large requirement for treatments with less adverse events on, e.g., blood pressure and sexual function: phytotherapy may be the right way to fill this need. Serenoa repens standardized extract has been widely studied and its ability to reduce lower urinary tract symptoms related to benign prostatic hyperplasia is comprehensively described in literature. An innovative investigation on the mechanism of inhibition of 5α-reductase by Serenoa repens extract active principles is proposed in this work through computational methods, performing molecular docking simulations on the crystal structure of human liver 5β-reductase. The results confirm that both sterols and fatty acids can play a role in the inhibition of the enzyme, thus, suggesting a competitive mechanism of inhibition. This work proposes a further confirmation for the rational use of herbal products in the management of benign prostatic hyperplasia, and suggests computational methods as an innovative, low cost, and non-invasive process for the study of phytocomplex activity toward proteic targets. PMID:27904805

Vibro-acoustography with 1.75D ultrasound array transducer for detection and localization of permanent prostate brachytherapy seeds: ex vivo study

NASA Astrophysics Data System (ADS)

Mehrmohammadi, Mohammad; Alizad, Azra; Kinnick, Randall R.; Davis, Brian J.; Fatemi, Mostafa

2013-03-01

Effective brachytherapy procedures require precise placement of radioactive seeds in the prostate. Currently, transrectal ultrasound (TRUS) imaging is one of the main intraoperative imaging modalities to assist physicians in placement of brachytherapy seeds. However, the seed detection rate with TRUS is poor mainly because ultrasound imaging is highly sensitive to variations in seed orientation. The purpose of this study is to investigate the abilities of a new acoustic radiation force imaging modality, vibro-acoustography (VA), equipped with a 1.75D array transducer and implemented on a customized clinical ultrasound scanner, to image and localize brachytherapy seeds in prostatic tissue. To perform experiments, excised cadaver prostate specimens were implanted with dummy brachytherapy seeds, and embedded in tissue mimicking gel to simulate the properties of the surrounding soft tissues. The samples were scanned using the VA system and the resulting VA signals were used to reconstruct VA images at several depths inside the tissue. To further evaluate the performance of VA in detecting seeds, X-ray computed tomography (CT) images of the same tissue sample, were obtained and used as a gold-standard to compare the number of seeds detected by the two methods. Our results indicate that VA is capable of imaging of brachytherapy seeds with accuracy and high contrast, and can detect a large percentage of the seeds implanted within the tissue samples.

Monte Carlo study of the impact of a magnetic field on the dose distribution in MRI-guided HDR brachytherapy using Ir-192

NASA Astrophysics Data System (ADS)

Beld, E.; Seevinck, P. R.; Lagendijk, J. J. W.; Viergever, M. A.; Moerland, M. A.

2016-09-01

In the process of developing a robotic MRI-guided high-dose-rate (HDR) prostate brachytherapy treatment, the influence of the MRI scanner’s magnetic field on the dose distribution needs to be investigated. A magnetic field causes a deflection of electrons in the plane perpendicular to the magnetic field, and it leads to less lateral scattering along the direction parallel with the magnetic field. Monte Carlo simulations were carried out to determine the influence of the magnetic field on the electron behavior and on the total dose distribution around an Ir-192 source. Furthermore, the influence of air pockets being present near the source was studied. The Monte Carlo package Geant4 was utilized for the simulations. The simulated geometries consisted of a simplified point source inside a water phantom. Magnetic field strengths of 0 T, 1.5 T, 3 T, and 7 T were considered. The simulation results demonstrated that the dose distribution was nearly unaffected by the magnetic field for all investigated magnetic field strengths. Evidence was found that, from a dose perspective, the HDR prostate brachytherapy treatment using Ir-192 can be performed safely inside the MRI scanner. No need was found to account for the magnetic field during treatment planning. Nevertheless, the presence of air pockets in close vicinity to the source, particularly along the direction parallel with the magnetic field, appeared to be an important point for consideration.

Monte Carlo study of the impact of a magnetic field on the dose distribution in MRI-guided HDR brachytherapy using Ir-192.

PubMed

Beld, E; Seevinck, P R; Lagendijk, J J W; Viergever, M A; Moerland, M A

2016-09-21

In the process of developing a robotic MRI-guided high-dose-rate (HDR) prostate brachytherapy treatment, the influence of the MRI scanner's magnetic field on the dose distribution needs to be investigated. A magnetic field causes a deflection of electrons in the plane perpendicular to the magnetic field, and it leads to less lateral scattering along the direction parallel with the magnetic field. Monte Carlo simulations were carried out to determine the influence of the magnetic field on the electron behavior and on the total dose distribution around an Ir-192 source. Furthermore, the influence of air pockets being present near the source was studied. The Monte Carlo package Geant4 was utilized for the simulations. The simulated geometries consisted of a simplified point source inside a water phantom. Magnetic field strengths of 0 T, 1.5 T, 3 T, and 7 T were considered. The simulation results demonstrated that the dose distribution was nearly unaffected by the magnetic field for all investigated magnetic field strengths. Evidence was found that, from a dose perspective, the HDR prostate brachytherapy treatment using Ir-192 can be performed safely inside the MRI scanner. No need was found to account for the magnetic field during treatment planning. Nevertheless, the presence of air pockets in close vicinity to the source, particularly along the direction parallel with the magnetic field, appeared to be an important point for consideration.

Simulation Using Novel Equipment Designed to Explain Spirometric Abnormalities in Respiratory Disease Enhances Learning in Higher Cognitive Domains

ERIC Educational Resources Information Center

Jamison, J. P.; Stewart, M. T.

2015-01-01

Simulation of disorders of respiratory mechanics shown by spirometry provides insight into the pathophysiology of disease but some clinically important disorders have not been simulated and none have been formally evaluated for education. We have designed simple mechanical devices which, along with existing simulators, enable all the main…

Primary cilia are increased in number and demonstrate structural abnormalities in human cancer.

PubMed

Yasar, Binnaz; Linton, Kim; Slater, Christian; Byers, Richard

2017-07-01

Primary cilia play an important role in the regulation of cell signalling pathways and are thought to have a role in cancer but have seldom been studied in human cancer samples. Primary cilia were visualised by dual immunofluorescence for anti-CROCC (ciliary rootlet coiled-coil) and anti-tubulin in a range of human cancers (including carcinomas of stomach, pancreas, prostate, lung and colon, lobular and ductal breast cancers and follicular lymphoma) and in matched normal tissue (stomach, pancreas, lung, large and small intestines, breast and reactive lymph nodes) samples using a tissue microarray; their frequency, association with proliferation, was measured by Ki-67 staining and their structure was analysed. Compared with normal tissues, primary cilia frequency was significantly elevated in adenocarcinoma of the lung (2.75% vs 1.85%, p=0.016), adenocarcinoma of the colon (3.80% vs 2.43%, respectively, p=0.017), follicular lymphoma (1.18% vs 0.83%, p=0.003) and pancreatic adenocarcinoma (7.00% vs 5.26%, p=0.002); there was no statistically significant difference compared with normal control tissue for gastric and prostatic adenocarcinomas or for lobular and ductal breast cancers. Additionally, structural abnormalities of primary cilia were identified in cancer tissues, including elongation of the axoneme, multiple basal bodies and branching of the axoneme. Ki-67 scores ranged from 0.7% to 78.4% and showed no statistically significant correlation with primary cilia frequency across all tissues (p=0.1501). The results show upregulation of primary cilia and the presence of structural defects in a wide range of human cancer tissue samples demonstrating association of dysregulation of primary cilia with human cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Combination of Tramadol and Lidocaine for Pain Control During Transrectal Ultrasound-guided Prostate Biopsy: A Randomized Double-blinded Study.

PubMed

Sen, Haluk; Seckiner, Ilker; Bayrak, Omer; Sen, Elzem; Erturhan, Sakip; Yagci, Faruk

2015-06-01

To evaluate the efficacy of tramadol, lidocaine, and a combination of tramadol with lidocaine in pain relief using periprostatic nerve block technique by guidance of transrectal ultrasound (TRUS) before the prostate biopsy (PBx). For the indication of TRUS-PBx, the patients with a prostate-specific antigen (PSA) level >4.0 ng/mL or abnormal digital examination findings were selected. The patients were randomized through random method. Group 1: patients were administered 5 mL of 2% lidocaine; group 2: patients were administered 5 mL of 25-mg tramadol; and group 3: patients were administered 5 mL of 2% lidocaine + 25-mg tramadol. The procedures were completed in 10 minutes, and a visual pain scale was administered to the patients to question the pain severity. TRUS-guided PBx was performed in 60 patients with an age range of 57-77 years (mean age, 66.2 ± 7.49 years) and a PSA range of 1-1000 ng/mL. The mean PSA level of the groups was 28.5 (±7.5), 16.1 (±5.0), and 14.9 (±2.9) ng/mL, respectively. The postprocedural pain scores by visual pain scale were 4.6 ± 1.2, 5.4 ± 1.2, and 3.6 ± 0.9 in lidocaine, tramadol, and lidocaine + tramadol groups, respectively. Periprostatic nerve block is the current golden standard method owing to pain management and comfort provided, independent of the patient age and the number of core biopsies. We suggest that tramadol may also be used in this field to achieve better pain management by improving lidocaine's effect or as an alternative to lidocaine. Copyright © 2015 Elsevier Inc. All rights reserved.

Pyranocoumarin Tissue Distribution, Plasma Metabolome and Prostate Transcriptome Impacts of Sub-Chronic Exposure to Korean Angelica Supplement in Mice.

PubMed

Zhang, Jinhui; Li, Li; Tang, Suni; Zhang, Yong; Markiewski, Maciej; Xing, Chengguo; Jiang, Cheng; Lü, Junxuan

2016-01-01

Herbal products containing Korean Angelica gigas Nakai (AGN) root extract are marketed as dietary supplements for memory enhancement, pain killing, and female menopausal symptom relief. We have shown the anticancer activities of AGN supplements in mouse models. To facilitate human anticancer translational research, we characterized the tissue distribution of AGN marker pyranocoumarin compounds decursin (D) and decursinol angelate (DA) ([Formula: see text]% in AGN) and their metabolite decursinol (DOH), assessed the safety of sub-chronic AGN dietary exposure in mice, and explored its impact on plasma aqueous metabolites and the prostate transcriptome. The data show that after a gavage dose, plasma contained readily detectable DOH, but little D and DA, mirroring patterns in the liver. Extra-hepatic tissues retained greater levels of DA and D than the liver did. For sub-chronic exposures, male mice were provided ad libitum AIN93M-pellet diets with 0.5 and 1% AGN for six weeks. No adverse effects were observed on the plasma biochemistry markers of liver and kidney integrity in spite of their enlargement. Histopathological examinations of the liver, kidney and other visceral organs did not reveal tissue abnormalities. Metabolomic assessment of plasma from mice fed the 1%-AGN diet suggested metabolic shifts of key amino acids especially in the methionine-cysteine cycle, purine cycle, and glycolysis-citrate cycle. Prostate transcriptomic profiling identified gene signature changes in the metabolisms of drugs, lipids and cellular energetics, neuro-muscular features, immunity and inflammation, and tumor suppressor/oncogene balance. The safety profile was corroborated with a daily [Formula: see text] injection of AGN extract (100-300[Formula: see text]mg/kg) for four weeks, which resulted in much greater systemic pyranocoumarin exposure than the dietary route did.

Pyranocoumarin tissue distribution, and plasma metabolome and prostate transcriptome impacts of sub-chronic exposure to Korean Angelica supplement in mice

PubMed Central

ZHANG, Jinhui; LI, Li; TANG, Suni; ZHANG, Yong; MARKIEWSKI, Maciej; XING, Chengguo; JIANG, Cheng; LÜ, Junxuan

2016-01-01

Herbal products containing Korean Angelica gigas Nakai (AGN) root extract are marketed as dietary supplements for memory enhancement, pain killing, and female menopausal symptom relief. We have shown anti-cancer activity of AGN supplement in mouse models. To facilitate human anti-cancer translational research, we characterized the tissue distribution of AGN marker pyranocoumarin compounds decursin (D) and decursinol angelate (DA) (~50% in AGN) and their metabolite decursinol (DOH), assessed safety of sub-chronic AGN dietary exposure in mice, and explored the impacts on the plasma aqueous metabolites and prostate transcriptome. The data show that after a gavage dose, plasma contained readily detectable DOH, but little D and DA, mirroring patterns in the liver. Extra-hepatic tissues retained greater level of DA and D than liver. For sub-chronic exposures, male mice were provided ad libitum AIN93M-pellet diet with 0.5 and 1% AGN for 6 weeks. No adverse effect was observed on plasma biochemistry markers of liver and kidney integrity in spite of their enlargement. Histopathological examination of liver, kidney and other visceral organs did not reveal tissue abnormalities. Metabolomic assessment of plasma from the mice fed 1%-AGN diet suggested metabolic shifts of key amino acids especially methionine-cysteine cycle, purine cycle and glycolysis-citrate cycle. Prostate transcriptomic profiling identified gene signature changes of metabolisms of drugs, lipids and cellular energetics, neuro-muscular features, immunity and inflammation, and tumor suppressor/oncogene balance. The safety profile was corroborated with daily i.p. injection of AGN extract (200 mg/kg) for 4 weeks, which resulted in much greater systemic pyranocoumarin exposure than dietary route. PMID:27080944

Cost-Savings Analysis of AR-V7 Testing in Patients With Metastatic Castration-Resistant Prostate Cancer Eligible for Treatment With Abiraterone or Enzalutamide.

PubMed

Markowski, Mark C; Frick, Kevin D; Eshleman, James R; Luo, Jun; Antonarakis, Emmanuel S

2016-12-01

Identification of cancer biomarkers that inform clinical decisions and reduce the use of ineffective therapies is a major goal of precision oncology. An abnormal splice variant of the androgen receptor, AR-V7, was recently found to confer resistance to novel hormonal therapies (abiraterone and enzalutamide) in men with metastatic castration-resistant prostate cancer (mCRPC), but did not negatively affect responses to taxane chemotherapies, suggesting that early use of chemotherapy may be a more effective option for AR-V7(+) patients. We calculated the cost savings of performing AR-V7 testing in mCRPC patients prior to starting abiraterone/enzalutamide (and avoiding these drugs in AR-V7(+) men) versus treating all mCRPC patients empirically with abiraterone/enzalutamide (without use of the biomarker). We determined that AR-V7 testing would result in substantial cost savings as long as the true prevalence of AR-V7 was >5%. In our prior studies, we estimated that approximately 30% of mCRPC patients may have detectable AR-V7 in circulating tumor cells (CTCs). In this population, upfront testing of AR-V7 status (at a price of $1,000 per test) would result in a net cost savings of $150 Million in the United States per year. AR-V7 testing in mCRPC patients would be cost-beneficial when considering the current price of treatment, and may reduce the ineffective use of abiraterone/enzalutamide, leading to a significant net cost savings to the healthcare system. Clinical-grade AR-V7 testing is currently available at our institution. Prostate 76:1484-1490, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

PTEN loss promotes intratumoral androgen synthesis and tumor microenvironment remodeling via aberrant activation of RUNX2 in castration-resistant prostate cancer

PubMed Central

Yang, Yinhui; Bai, Yang; He, Yundong; Zhao, Yu; Chen, Jiaxiang; Ma, Linlin; Pan, Yunqian; Hinten, Michael; Zhang, Jun; Karnes, R. Jeffrey; Kohli, Manish; Westendorf, Jennifer J.; Li, Benyi; Zhu, Runzhi; Huang, Haojie; Xu, Wanhai

2018-01-01

Purpose Intratumoral androgen synthesis (IAS) is a key mechanism promoting androgen receptor (AR)reactivation and anti-androgen resistance in castration-resistant prostate cancer (CRPC). However, signaling pathways driving aberrant IAS remain poorly understood. Experimental Design The effect of components of the AKT-RUNX2-osteocalcin (OCN)-GPRC6A-CREB signaling axis on expression of steroidogenesis genes CYP11A1 and CYP17A1 and testosterone level were examined in PTEN-null human PCa cell lines. Pten knockout mice were employed to examine the effect of Runx2 heterozygous deletion or abiraterone acetate (ABA), a prodrug of the CYP17A1 inhibitor abiraterone on Cyp11a1 and Cyp17a1 expression, testosterone level and tumor microenvironment (TME) remodeling in vivo. Results We uncovered that activation of the AKT-RUNX2-OCN-GPRC6A-CREB signaling axis induced expression of CYP11A1 and CYP17A1 and testosterone production in PTEN-null PCa cell lines in culture. Deletion of Runx2 in Pten homozygous knockout prostate tumors decreased Cyp11a1 and Cyp17a1 expression, testosterone level and tumor growth in castrated mice. ABA treatment also inhibited testosterone synthesis and alleviated Pten loss-induced tumorigenesis in vivo. Pten deletion induced TME remodeling, but Runx2 heterozygous deletion or ABA treatment reversed the effect of Pten loss by decreasing expression of the collagenase Mmp9. Conclusions Abnormal RUNX2 activation plays a pivotal role in PTEN loss-induced IAS and TME remodeling, suggesting that the identified signaling cascade represents a viable target for effective treatment of PTEN-null PCa including CRPC. PMID:29167276

EMP combination chemotherapy and low-dose monotherapy in advanced prostate cancer.

PubMed

Kitamura, Tadaichi; Nishimatsu, Hiroaki; Hamamoto, Toshiaki; Tomita, Kyoichi; Takeuchi, Takumi; Ohta, Nobutaka

2002-02-01

Many chemotherapeutic regimens combined with estramustine phosphate (EMP) have been elaborated for the treatment of hormone-refractory prostate cancer over 30 years. However, older EMP-based combination chemotherapies with vinblastine, vinorelbine, doxorubicin or cyclophosphamide showed relatively low PSA response rate (25-58%) accompanied with high toxicities. On the other hand, newly developed EMP-based combination regimens with etoposide, pacitaxel, carboplatin or docetaxel demonstrated promising PSA response rate (43-77%) with moderate to severe toxicity in the rate of thromboembolic event (5-18%) and of neutropenia (9-41%). Treatment-related death was less in the latter combination group (5/615, 0.8%) than that in the former group (3/234, 1.3%). Of note, in the docetaxel combination with EMP, PSA response rate is as high as 77% with high rate (41%) of neutropenia but no treatment-related death was observed. Docetaxel combination with EMP seems to be the best regimen, though not completely justified by randomized trials, to be selected in the modern era, which will be followed by paclitaxel, carboplatin and EMP combination with PSA response rate of 71%. In addition, an interim report in 83 patients was presented. They were not consecutively enrolled but were treated on low-dose EMP monotherapy for previously untreated advanced prostate cancer in Department of Urology of Tokyo University and our 21 affiliated hospitals. Overall PSA response rate was as high as 93.4% out of 76 assessable patients. However, overall toxicity rate was abnormally high (39.5%) with drug discontinuation rate of 32.1%. The reason of low drug compliance may be attributed to gastrointestinal symptoms. To overcome the low drug compliance, appropriate patients for EMP administration should be selected by using gene analysis on the basis of sophisticated tailor-made medicine.

Utilizing Functionalized Nano-Paterned Surfaces as a clue to Cell Metastasis in Prostate and Breast Cancer

NASA Astrophysics Data System (ADS)

Matthews, James; Bastatas, Lyndon

2012-03-01

There is a direct relation between the survival of a patient diagnosed with prostate or breast cancer and the metastatic potential of the patient's cancer. It is therefore extremely important to prognose metastatic potentials. In this study we investigated whether the behaviors of cancer cells responding to our state of the art nano-patterns differ by the metastatic potential of the cancer cells. We have used lowly (LNCaP) and highly (CL-1) metastatic human prostate cancer cells and lowly (MCF-7) and highly (MB231) metastatic breast cancer cells. A surface functionalization study was then performed first on uniform gold and glass surfaces, then on gold nano-patterned surfaces made by nano-sphere lithography using nano-spheres in diameter of 200nm to 800nm. The gold surfaces were functionalized with fibronectin (FN) and confirmed through XPS analysis. The CL-1, MCF-7, and MB231 cells show similar proliferation on all surfaces regardless of the presence of FN, whereas LNCaP show a clear preference for FN coated surfaces. The proliferation of the LNCaP was reduced when grown on finer nano-scaffolds, but the more aggressive CL-1, MB231, and MCF-7 cells show an abnormal proliferation regardless of pattern size. The difference in adhesion is intrinsic and was verified through dual fluorescent imaging. Clear co-localization of actin-vinculin were found on CL-1, MCF-7, and MB231. However LNCaP cells showed the co-localization only on the tips of the cells. These results provide vital clues to the bio-mechanical differences between the cancer cells with different metastatic potential.

Exploring the Interaction Mechanism Between Cyclopeptide DC3 and Androgen Receptor Using Molecular Dynamics Simulations and Free Energy Calculations

PubMed Central

Zhang, Huimin; Song, Tianqing; Yang, Yizhao; Fu, Chenggong; Li, Jiazhong

2018-01-01

Androgen receptor (AR) is a key target in the discovery of anti-PCa (Prostate Cancer) drugs. Recently, a novel cyclopeptide Diffusa Cyclotide-3 (DC3), isolated from Hedyotisdiffusa, has been experimentally demonstrated to inhibit the survival and growth of LNCap cells, which typically express T877A-mutated AR, the most frequently detected point mutation of AR in castration-resistant prostate cancer (CRPC). But the interaction mechanism between DC3 and AR is not clear. Here in this study we aim to explore the possible binding mode of DC3 to T877A-mutated AR from molecular perspective. Firstly, homology modeling was employed to construct the three-dimensional structure of the cyclopeptide DC3 using 2kux.1.A as the template. Then molecular docking, molecular dynamics (MD) simulations, and molecular mechanics/generalized Born surface area (MM-GBSA) methods were performed to determine the bind site and explore the detailed interaction mechanism of DC3-AR complex. The obtained results suggested that the site formed by H11, loop888-893, and H12 (site 2) was the most possible position of DC3 binding to AR. Besides, hydrogen bonds, hydrophobic, and electrostatic interactions play dominant roles in the recognition and combination of DC3-AR complex. The essential residues dominant in each interaction were specifically revealed. This work facilitates our understanding of the interaction mechanism of DC3 binding to AR at the molecular level and contributes to the rational cyclopeptide drug design for prostate cancer. PMID:29755968

Exploring the Interaction Mechanism between Cyclopeptide DC3 and Androgen Receptor Using Molecular Dynamics Simulations and Free Energy Calculations

NASA Astrophysics Data System (ADS)

Zhang, Huimin; Song, Tianqing; Yang, Yizhao; Fu, Chenggong; Li, Jiazhong

2018-04-01

Androgen receptor (AR) is a key target in the discovery of anti-PCa (Prostate Cancer) drugs. Recently, a novel cyclopeptide Diffusa Cyclotide-3 (DC3), isolated from Hedyotisdiffusa, has been experimentally demonstrated to inhibit the survival and growth of LNCap cells, which typically express T877A-mutated AR, the most frequently detected point mutation of AR in castration-resistant prostate cancer (CRPC). But the interaction mechanism between DC3 and AR is not clear. Here in this study we aim to explore the possible binding mode of DC3 to T877A-mutated AR from molecular perspective. Firstly, homology modeling was employed to construct the three-dimensional structure of the cyclopeptide DC3 using 2kux.1.A as the template. Then molecular docking, molecular dynamics (MD) simulations and molecular mechanics/generalized Born surface area (MM-GBSA) methods were performed to determine the bind site and explore the detailed interaction mechanism of DC3-AR complex. The obtained results suggested that the site formed by H11, loop888-893 and H12 (site 2) was the most possible position of DC3 binding to AR. Besides, hydrogen bonds, hydrophobic and electrostatic interactions play dominant roles in the recognition and combination of DC3-AR complex. The essential residues dominant in each interaction were specifically revealed. This work facilitates our understanding of the interaction mechanism of DC3 binding to AR at the molecular level and contributes to the rational cyclopeptide drug design for prostate cancer.

Exploring the Interaction Mechanism Between Cyclopeptide DC3 and Androgen Receptor Using Molecular Dynamics Simulations and Free Energy Calculations.

PubMed

Zhang, Huimin; Song, Tianqing; Yang, Yizhao; Fu, Chenggong; Li, Jiazhong

2018-01-01

Androgen receptor (AR) is a key target in the discovery of anti-PCa (Prostate Cancer) drugs. Recently, a novel cyclopeptide Diffusa Cyclotide-3 (DC3), isolated from Hedyotisdiffusa , has been experimentally demonstrated to inhibit the survival and growth of LNCap cells, which typically express T877A-mutated AR, the most frequently detected point mutation of AR in castration-resistant prostate cancer (CRPC). But the interaction mechanism between DC3 and AR is not clear. Here in this study we aim to explore the possible binding mode of DC3 to T877A-mutated AR from molecular perspective. Firstly, homology modeling was employed to construct the three-dimensional structure of the cyclopeptide DC3 using 2kux.1.A as the template. Then molecular docking, molecular dynamics (MD) simulations, and molecular mechanics/generalized Born surface area (MM-GBSA) methods were performed to determine the bind site and explore the detailed interaction mechanism of DC3-AR complex. The obtained results suggested that the site formed by H11, loop888-893, and H12 (site 2) was the most possible position of DC3 binding to AR. Besides, hydrogen bonds, hydrophobic, and electrostatic interactions play dominant roles in the recognition and combination of DC3-AR complex. The essential residues dominant in each interaction were specifically revealed. This work facilitates our understanding of the interaction mechanism of DC3 binding to AR at the molecular level and contributes to the rational cyclopeptide drug design for prostate cancer.

Identification of aberrant gene expression associated with aberrant promoter methylation in primordial germ cells between E13 and E16 rat F3 generation vinclozolin lineage.

PubMed

Taguchi, Y-h

2015-01-01

Transgenerational epigenetics (TGE) are currently considered important in disease, but the mechanisms involved are not yet fully understood. TGE abnormalities expected to cause disease are likely to be initiated during development and to be mediated by aberrant gene expression associated with aberrant promoter methylation that is heritable between generations. However, because methylation is removed and then re-established during development, it is not easy to identify promoter methylation abnormalities by comparing normal lineages with those expected to exhibit TGE abnormalities. This study applied the recently proposed principal component analysis (PCA)-based unsupervised feature extraction to previously reported and publically available gene expression/promoter methylation profiles of rat primordial germ cells, between E13 and E16 of the F3 generation vinclozolin lineage that are expected to exhibit TGE abnormalities, to identify multiple genes that exhibited aberrant gene expression/promoter methylation during development. The biological feasibility of the identified genes were tested via enrichment analyses of various biological concepts including pathway analysis, gene ontology terms and protein-protein interactions. All validations suggested superiority of the proposed method over three conventional and popular supervised methods that employed t test, limma and significance analysis of microarrays, respectively. The identified genes were globally related to tumors, the prostate, kidney, testis and the immune system and were previously reported to be related to various diseases caused by TGE. Among the genes reported by PCA-based unsupervised feature extraction, we propose that chemokine signaling pathways and leucine rich repeat proteins are key factors that initiate transgenerational epigenetic-mediated diseases, because multiple genes included in these two categories were identified in this study.

Identification of aberrant gene expression associated with aberrant promoter methylation in primordial germ cells between E13 and E16 rat F3 generation vinclozolin lineage

PubMed Central

2015-01-01

Background Transgenerational epigenetics (TGE) are currently considered important in disease, but the mechanisms involved are not yet fully understood. TGE abnormalities expected to cause disease are likely to be initiated during development and to be mediated by aberrant gene expression associated with aberrant promoter methylation that is heritable between generations. However, because methylation is removed and then re-established during development, it is not easy to identify promoter methylation abnormalities by comparing normal lineages with those expected to exhibit TGE abnormalities. Methods This study applied the recently proposed principal component analysis (PCA)-based unsupervised feature extraction to previously reported and publically available gene expression/promoter methylation profiles of rat primordial germ cells, between E13 and E16 of the F3 generation vinclozolin lineage that are expected to exhibit TGE abnormalities, to identify multiple genes that exhibited aberrant gene expression/promoter methylation during development. Results The biological feasibility of the identified genes were tested via enrichment analyses of various biological concepts including pathway analysis, gene ontology terms and protein-protein interactions. All validations suggested superiority of the proposed method over three conventional and popular supervised methods that employed t test, limma and significance analysis of microarrays, respectively. The identified genes were globally related to tumors, the prostate, kidney, testis and the immune system and were previously reported to be related to various diseases caused by TGE. Conclusions Among the genes reported by PCA-based unsupervised feature extraction, we propose that chemokine signaling pathways and leucine rich repeat proteins are key factors that initiate transgenerational epigenetic-mediated diseases, because multiple genes included in these two categories were identified in this study. PMID:26677731

Relation of comorbidities and patient navigation with the time to diagnostic resolution after abnormal cancer screening.

PubMed

Whitley, Elizabeth M; Raich, Peter C; Dudley, Donald J; Freund, Karen M; Paskett, Electra D; Patierno, Steven R; Simon, Melissa; Warren-Mears, Victoria; Snyder, Frederick R

2017-01-01

Whether patient navigation improves outcomes for patients with comorbidities is unknown. The aims of this study were to determine the effect of comorbidities on the time to diagnostic resolution after an abnormal cancer screening test and to examine whether patient navigation improves the timeliness and likelihood of diagnostic resolution for patients with comorbidities in comparison with no navigation. A secondary analysis of comorbidity data collected by Patient Navigation Research Program sites using the Charlson Comorbidity Index (CCI) was conducted. The participants were 6,349 patients with abnormal breast, cervical, colon, or prostate cancer screening tests between 2007 and 2011. The intervention was patient navigation or usual care. The CCI data were highly skewed across projects and cancer sites, and the CCI scores were categorized as 0 (CCI score of 0 or no comorbidities identified; 76% of cases); 1 (CCI score of 1; 16% of cases), or 2 (CCI score ≥ 2; 8% of cases). Separate adjusted hazard ratios for each site and cancer type were obtained, and then they were pooled with a meta-analysis random effects methodology. Patients with a CCI score ≥ 2 had delayed diagnostic resolution after an abnormal cancer screening test in comparison with those with no comorbidities. Patient navigation reduced delays in diagnostic resolution, with the greatest benefits seen for those with a CCI score ≥ 2. Persons with a CCI score ≥ 2 experienced significant delays in timely diagnostic care in comparison with patients without comorbidities. Patient navigation was effective in reducing delays in diagnostic resolution among those with CCI scores > 1. Cancer 2017;123:312-318. © 2016 American Cancer Society. © 2016 American Cancer Society.

Treatment planning for prostate focal laser ablation in the face of needle placement uncertainty

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cepek, Jeremy, E-mail: jcepek@robarts.ca; Fenster, Aaron; Lindner, Uri

2014-01-15

Purpose: To study the effect of needle placement uncertainty on the expected probability of achieving complete focal target destruction in focal laser ablation (FLA) of prostate cancer. Methods: Using a simplified model of prostate cancer focal target, and focal laser ablation region shapes, Monte Carlo simulations of needle placement error were performed to estimate the probability of completely ablating a region of target tissue. Results: Graphs of the probability of complete focal target ablation are presented over clinically relevant ranges of focal target sizes and shapes, ablation region sizes, and levels of needle placement uncertainty. In addition, a table ismore » provided for estimating the maximum target size that is treatable. The results predict that targets whose length is at least 5 mm smaller than the diameter of each ablation region can be confidently ablated using, at most, four laser fibers if the standard deviation in each component of needle placement error is less than 3 mm. However, targets larger than this (i.e., near to or exceeding the diameter of each ablation region) require more careful planning. This process is facilitated by using the table provided. Conclusions: The probability of completely ablating a focal target using FLA is sensitive to the level of needle placement uncertainty, especially as the target length approaches and becomes greater than the diameter of ablated tissue that each individual laser fiber can achieve. The results of this work can be used to help determine individual patient eligibility for prostate FLA, to guide the planning of prostate FLA, and to quantify the clinical benefit of using advanced systems for accurate needle delivery for this treatment modality.« less

Optimal timing of oral fosfomycin administration for pre-prostate biopsy prophylaxis.

PubMed

Rhodes, Nathaniel J; Gardiner, Bradley J; Neely, Michael N; Grayson, M Lindsay; Ellis, Andrew G; Lawrentschuk, Nathan; Frauman, Albert G; Maxwell, Kelly M; Zembower, Teresa R; Scheetz, Marc H

2015-07-01

As the optimal administration time for fosfomycin peri-procedural prophylaxis is unclear, we sought to determine optimal administration times for fosfomycin peri-procedural prophylaxis. Plasma, peripheral zone and transition zone fosfomycin concentrations were obtained from 26 subjects undergoing transurethral resection of the prostate (TURP), following a single oral dose of 3 g of fosfomycin. Population pharmacokinetic modelling was completed with the Nonparametric Adaptive Grid (NPAG) algorithm (Pmetrics package for R), with a four-compartment model. Plasma and tissue concentrations were simulated during the first 24 h post-dose, comparing these with EUCAST susceptibility breakpoints for Escherichia coli, a common uropathogen. Non-compartmental-determined pharmacokinetic values in our population were similar to those reported in the package insert. Predicted plasma concentrations rapidly increased after the first hour, giving more than 90% population coverage for organisms with an MIC ≤4 mg/L over the first 12 h post-dose. Organisms with higher MICs fared much worse, with organisms at the EUCAST breakpoint being covered for <10% of the population at any time. Transitional zone prostate concentrations exceeded 4 mg/L for 90% of the population between hours 1 and 9. Peripheral zone prostate concentrations were much lower and only exceeded 4 mg/L for 70% of the population between hours 1 and 4. Until more precise plasma and tissue data are available, we recommend that fosfomycin prophylaxis be given 1-4 h prior to prostate biopsy. We do not recommend fosfomycin prophylaxis for subjects with known organisms with MICs >4 mg/L. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The treatment effects of flaxseed-derived secoisolariciresinol diglycoside and its metabolite enterolactone on benign prostatic hyperplasia involve the G protein-coupled estrogen receptor 1.

PubMed

Ren, Guan-Yu; Chen, Chun-Yang; Chen, Wei-Guo; Huang, Ya; Qin, Li-Qiang; Chen, Li-Hua

2016-12-01

Secoisolariciresinol diglucoside (SDG), a lignan extracted from flaxseed, has been shown to suppress benign prostatic hyperplasia (BPH). However, little is known about the mechanistic basis for its anti-BPH activity. The present study showed that enterolactone (ENL), the mammalian metabolite of SDG, shared the similar binding site of G1 on a new type of membranous estrogen receptor, G-protein-coupled estrogen eceptor 1 (GPER), by docking simulations method. ENL and G1 (the specific agonist of GPER) inhibited the proliferation of human prostate stromal cell line WPMY-1 as shown by MTT assay and arrested cell cycle at the G0/G1 phase, which was displayed by propidium iodide staining following flow cytometer examination. Silencing GPER by short interfering RNA attenuated the inhibitory effect of ENL on WPMY-1 cells. The therapeutic potential of SDG in the treatment of BPH was confirmed in a testosterone propionate-induced BPH rat model. SDG significantly reduced the enlargement of the rat prostate and the number of papillary projections of prostatic alveolus and thickness of the pseudostratified epithelial and stromal cells when comparing with the model group. Mechanistic studies showed that SDG and ENL increased the expression of GPER both in vitro and in vivo. Furthermore, ENL-induced cell cycle arrest may be mediated by the activation of GPER/ERK pathway and subsequent upregulation of p53 and p21 and downregulation of cyclin D1. This work, in tandem with previous studies, will enhance our knowledge regarding the mechanism(s) of dietary phytochemicals on BPH prevention and ultimately expand the scope of adopting alternative approaches in BPH treatment.

Mathematical modeling of human brain physiological data

NASA Astrophysics Data System (ADS)

Böhm, Matthias; Faltermeier, Rupert; Brawanski, Alexander; Lang, Elmar W.

2013-12-01

Recently, a mathematical model of the basic physiological processes regulating the cerebral perfusion and oxygen supply was introduced [Jung , J. Math. Biol.JMBLAJ0303-681210.1007/s00285-005-0343-5 51, 491 (2005)]. Although this model correctly describes the interdependence of arterial blood pressure (ABP) and intracranial pressure (ICP), it fails badly when it comes to explaining certain abnormal correlations seen in about 80% of the recordings of ABP together with ICP and the partial oxygen pressure (TiPO2) of the neuronal tissue, taken at an intensive care unit during neuromonitoring of patients with a severe brain trauma. Such recordings occasionally show segments, where the mean arterial blood pressure is correlated with the partial oxygen pressure in tissue but anticorrelated with the intracranial pressure. The origin of such abnormal correlations has not been fully understood yet. Here, two extensions to the previous approach are proposed which can reproduce such abnormal correlations in simulations quantitatively. Furthermore, as the simulations are based on a mathematical model, additional insight into the physiological mechanisms from which such abnormal correlations originate can be gained.

Application of distributed optical fiber sensing technologies to the monitoring of leakage and abnormal disturbance of oil pipeline

NASA Astrophysics Data System (ADS)

Yang, Xiaojun; Zhu, Xiaofei; Deng, Chi; Li, Junyi; Liu, Cheng; Yu, Wenpeng; Luo, Hui

2017-10-01

To improve the level of management and monitoring of leakage and abnormal disturbance of long distance oil pipeline, the distributed optical fiber temperature and vibration sensing system is employed to test the feasibility for the healthy monitoring of a domestic oil pipeline. The simulating leakage and abnormal disturbance affairs of oil pipeline are performed in the experiment. It is demonstrated that the leakage and abnormal disturbance affairs of oil pipeline can be monitored and located accurately with the distributed optical fiber sensing system, which exhibits good performance in the sensitivity, reliability, operation and maintenance etc., and shows good market application prospect.

Effects of tumour necrosis factor α upon the metabolism of the endocannabinoid anandamide in prostate cancer cells.

PubMed

Karlsson, Jessica; Gouveia-Figueira, Sandra; Alhouayek, Mireille; Fowler, Christopher J

2017-01-01

Tumour necrosis factor α (TNFα) is involved in the pathogenesis of prostate cancer, a disease where disturbances in the endocannabinoid system are seen. In the present study we have investigated whether treatment of DU145 human prostate cancer cells affects anandamide (AEA) catabolic pathways. Additionally, we have investigated whether cyclooxygenase-2 (COX-2) can regulate the uptake of AEA into cells. Levels of AEA synthetic and catabolic enzymes were determined by qPCR. AEA uptake and hydrolysis in DU145 and RAW264.7 macrophage cells were assayed using AEA labeled in the arachidonic and ethanolamine portions of the molecule, respectively. Levels of AEA, related N-acylethanolamines (NAEs), prostaglandins (PG) and PG-ethanolamines (PG-EA) in DU145 cells and medium were quantitated by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. TNFα treatment of DU145 cells increased mRNA levels of PTSG2 (gene of COX-2) and decreased the mRNA of the AEA synthetic enzyme N-acyl-phosphatidylethanolamine selective phospholipase D. mRNA levels of the AEA hydrolytic enzymes fatty acid amide hydrolase (FAAH) and N-acylethanolamine-hydrolyzing acid amidase were not changed. AEA uptake in both DU145 and RAW264.7 cells was inhibited by FAAH inhibition, but not by COX-2 inhibition, even in RAW264.7 cells where the expression of this enzyme had greatly been induced by lipopolysaccharide + interferon γ treatment. AEA and related NAEs were detected in DU145 cells, but PGs and PGE2-EA were only detected when the cells had been preincubated with 100 nM AEA. The data demonstrate that in DU145 cells, TNFα treatment changes the relative expression of the enzymes involved in the hydrolytic and oxygenation catabolic pathways for AEA. In RAW264.7 cells, COX-2, in contrast to FAAH, does not regulate the cellular accumulation of AEA. Further studies are necessary to determine the extent to which inflammatory mediators are involved in the abnormal endocannabinoid signalling system in prostate cancer.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bednarz, Natalia; Eltze, Elke; Semjonow, Axel

A recent study concluded that serum prostate specific antigen (PSA)-based screening is beneficial for reducing the lethality of PCa, but was also associated with a high risk of 'overdiagnosis'. Nevertheless, also PCa patients who suffered from organ confined tumors and had negative bone scans succumb to distant metastases after complete tumor resection. It is reasonable to assume that those tumors spread to other organs long before the overt manifestation of metastases. Our current results confirm that prostate tumors are highly heterogeneous. Even a small subpopulation of cells bearing BRCA1 losses can initiate PCa cell regional and distant dissemination indicating thosemore » patients which might be at high risk of metastasis. A preliminary study performed on a small cohort of multifocal prostate cancer (PCa) detected BRCA1 allelic imbalances (AI) among circulating tumor cells (CTCs). The present analysis was aimed to elucidate the biological and clinical role of BRCA1 losses on metastatic spread and tumor progression in prostate cancer patients. Experimental Design: To map molecular progression in PCa outgrowth we used FISH analysis of tissue microarrays (TMA), lymph node sections and CTC from peripheral blood. We found that 14% of 133 tested patients carried monoallelic BRCA1 loss in at least one tumor focus. Extended molecular analysis of chr17q revealed that this aberration was often a part of larger cytogenetic rearrangement involving chr17q21 accompanied by AI of the tumor suppressor gene PTEN and lack of the BRCA1 promoter methylation. The BRCA1 losses correlated with advanced T stage (p < 0.05), invasion to pelvic lymph nodes (LN, p < 0.05) as well as BR (p < 0.01). Their prevalence was twice as high within 62 LN metastases (LNMs) as in primary tumors (27%, p < 0.01). The analysis of 11 matched primary PCa-LNM pairs confirmed the suspected transmission of genetic abnormalities between those two sites. In 4 of 7 patients with metastatic disease, BRCA1 losses appeared in a minute fraction of cytokeratin- and vimentin-positive CTCs. Small subpopulations of PCa cells bearing BRCA1 losses might be one confounding factor initiating tumor dissemination and might provide an early indicator of shortened disease-free survival.« less

Periostin: a novel prognostic and therapeutic target for genitourinary cancer?

PubMed

Nuzzo, Pier Vitale; Buzzatti, Giulia; Ricci, Francesco; Rubagotti, Alessandra; Argellati, Francesca; Zinoli, Linda; Boccardo, Francesco

2014-10-01

Many of the cellular abnormalities present in solid tumors are structural in nature and involve the proteins of the extracellular matrix (ECM). Periostin is a protein produced and secreted by the fibroblasts as a component of the ECM where it is involved in regulating intercellular adhesion. The expression of periostin has an important physiological role during embryogenesis and growth, namely at the level of bone, dental, and cardiac tissues. Many studies indicate that periostin plays an important role for tumor progression in various types of cancer, such as colon, lung, head and neck, breast, ovarian, and prostate. To the best of our knowledge, a limited number of studies have investigated periostin expression in urogenital cancer, such as prostate, bladder, penile, and renal cancer, and no studies were performed in testis cancer. In this review article, we summarize the most recent knowledge of periostin, its genetic and protein structure, and the role of the different isoforms identified and sequenced so far. In particular, we focus our attention on the role of this protein in genitourinary tumors, trying to emphasize the role not only as a possible prognostic marker, but also as a possible target for the development of future anticancer therapies. Copyright © 2014 Elsevier Inc. All rights reserved.

Cold Kit for Prostate-Specific Membrane Antigen (PSMA) PET Imaging: Phase 1 Study of 68Ga-Tris(Hydroxypyridinone)-PSMA PET/CT in Patients with Prostate Cancer.

PubMed

Hofman, Michael S; Eu, Peter; Jackson, Price; Hong, Emily; Binns, David; Iravani, Amir; Murphy, Declan; Mitchell, Catherine; Siva, Shankar; Hicks, Rodney J; Young, Jennifer D; Blower, Philip J; Mullen, Gregory E

2018-04-01

68 Ga-labeled urea-based inhibitors of the prostate-specific membrane antigen (PSMA), such as 68 Ga-labeled N , N '-bis(2-hydroxybenzyl)ethylenediamine- N , N '-diacetic acid (HBED)-PSMA-11, are promising small molecules for targeting prostate cancer. A new radiopharmaceutical, 68 Ga-labeled tris(hydroxypyridinone) (THP)-PSMA, has a simplified design for single-step kit-based radiolabeling. It features the THP ligand, which forms complexes with 68 Ga 3+ rapidly at a low concentration, at room temperature, and over a wide pH range, enabling direct elution from a 68 Ge/ 68 Ga generator into a lyophilized radiopharmaceutical kit in 1 step without manipulation. The aim of this phase 1 study was to assess the safety and biodistribution of 68 Ga-THP-PSMA. Methods: Cohort A comprised 8 patients who had proven prostate cancer and were scheduled to undergo prostatectomy; they had Gleason scores of 7-10 and a mean prostate-specific antigen level of 7.8 μg/L (range, 5.4-10.6 μg/L). They underwent PET/CT after the administration of 68 Ga-THP-PSMA. All patients proceeded to prostatectomy (7 with pelvic nodal dissection). Dosimetry from multi-time-point PET imaging was performed with OLINDA/EXM. Cohort B comprised 6 patients who had positive 68 Ga-HBED-PSMA-11 PET/CT scanning results and underwent comparative 68 Ga-THP-PSMA scanning. All patients were monitored for adverse events. Results: No adverse events occurred. In cohort A, 6 of 8 patients had focal uptake in the prostate (at 2 h: average SUV max , 5.1; range, 2.4-9.2) and correlative 3+ staining of prostatectomy specimens on PSMA immunohistochemistry. The 2 68 Ga-THP-PSMA scans with negative results had only 1+/2+ staining. The mean effective dose was 2.07E-02 mSv/MBq. In cohort B, 68 Ga-THP-PSMA had lower physiologic background uptake than 68 Ga-HBED-PSMA-11 (in the parotid glands, the mean SUV max for 68 Ga-THP-PSMA was 3.6 [compared with 19.2 for 68 Ga-HBED-PSMA-11]; the respective corresponding values in the liver were 2.7 and 6.3, and those in the spleen were 2.7 and 10.5; P < 0.001 for all). In 5 of 6 patients, there was concordance in the number of metastases identified with 68 Ga-HBED-PSMA-11 and 68 Ga-THP-PSMA. Thirteen of 15 nodal abnormalities were subcentimeter. In 22 malignant lesions, the tumor-to-liver contrast with 68 Ga-THP-PSMA was similar to that with 68 Ga-HBED-PSMA (4.7 and 5.4, respectively; P = 0.15), despite a higher SUV max for 68 Ga-HBED-PSMA than for 68 Ga-THP-PSMA (30.3 and 10.7, respectively; P < 0.01). Conclusion: 68 Ga-THP-PSMA is safe and has a favorable biodistribution for clinical imaging. Observed focal uptake in the prostate was localized to PSMA-expressing malignant tissue on histopathology. Metastatic PSMA-avid foci were also visualized with 68 Ga-THP-PSMA PET. Single-step production from a Good Manufacturing Practice cold kit may enable rapid adoption. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

The politics of plastics: the making and unmaking of bisphenol a "safety".

PubMed

Vogel, Sarah A

2009-11-01

Bisphenol A (BPA), a synthetic chemical used in the production of plastics since the 1950s and a known endocrine disruptor, is a ubiquitous component of the material environment and human body. New research on very-low-dose exposure to BPA suggests an association with adverse health effects, including breast and prostate cancer, obesity, neurobehavioral problems, and reproductive abnormalities. These findings challenge the long-standing scientific and legal presumption of BPA's safety. The history of how BPA's safety was defined and defended provides critical insight into the questions now facing lawmakers and regulators: is BPA safe, and if not, what steps must be taken to protect the public's health? Answers to both questions involve reforms in chemical policy, with implications beyond BPA.

Technical Pitfall in 68Ga-Prostate Specific Membrane Antigen Imaging: Altered Biodistribution Caused by Free 68Ga-Citrate Due to Radiolysis Showing Increased Vascular Activity.

PubMed

Hod, Nir; Anconina, Reut; Levin, Daniel; Ezroh Kazap, Dina; Lantsberg, Sophie

2018-06-01

As with any new molecular imaging modality, accurate characterization of abnormalities on Ga-PSMA PET/CT imaging can be accomplished only if one is aware of the normal distribution pattern, physiological variants, and potential sources of false imaging findings. Altered biodistribution can have a significant impact on scan interpretation. Presented here is a rare case in which radiopharmaceutical radiolysis occurred causing excessive free Ga-citrate showing as an increased vascular activity. As Ga-PSMA PET/CT imaging is a relatively new imaging technique, it is important to be aware of such a potential technical pitfall in clinical practice in order to prevent scan misinterpretation.

GGEMS-Brachy: GPU GEant4-based Monte Carlo simulation for brachytherapy applications

NASA Astrophysics Data System (ADS)

Lemaréchal, Yannick; Bert, Julien; Falconnet, Claire; Després, Philippe; Valeri, Antoine; Schick, Ulrike; Pradier, Olivier; Garcia, Marie-Paule; Boussion, Nicolas; Visvikis, Dimitris

2015-07-01

In brachytherapy, plans are routinely calculated using the AAPM TG43 formalism which considers the patient as a simple water object. An accurate modeling of the physical processes considering patient heterogeneity using Monte Carlo simulation (MCS) methods is currently too time-consuming and computationally demanding to be routinely used. In this work we implemented and evaluated an accurate and fast MCS on Graphics Processing Units (GPU) for brachytherapy low dose rate (LDR) applications. A previously proposed Geant4 based MCS framework implemented on GPU (GGEMS) was extended to include a hybrid GPU navigator, allowing navigation within voxelized patient specific images and analytically modeled 125I seeds used in LDR brachytherapy. In addition, dose scoring based on track length estimator including uncertainty calculations was incorporated. The implemented GGEMS-brachy platform was validated using a comparison with Geant4 simulations and reference datasets. Finally, a comparative dosimetry study based on the current clinical standard (TG43) and the proposed platform was performed on twelve prostate cancer patients undergoing LDR brachytherapy. Considering patient 3D CT volumes of 400  × 250  × 65 voxels and an average of 58 implanted seeds, the mean patient dosimetry study run time for a 2% dose uncertainty was 9.35 s (≈500 ms 10-6 simulated particles) and 2.5 s when using one and four GPUs, respectively. The performance of the proposed GGEMS-brachy platform allows envisaging the use of Monte Carlo simulation based dosimetry studies in brachytherapy compatible with clinical practice. Although the proposed platform was evaluated for prostate cancer, it is equally applicable to other LDR brachytherapy clinical applications. Future extensions will allow its application in high dose rate brachytherapy applications.

Calculated organ doses using Monte Carlo simulations in a reference male phantom undergoing HDR brachytherapy applied to localized prostate carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Candela-Juan, Cristian; Perez-Calatayud, Jose; Ballester, Facundo

Purpose: The aim of this study was to obtain equivalent doses in radiosensitive organs (aside from the bladder and rectum) when applying high-dose-rate (HDR) brachytherapy to a localized prostate carcinoma using {sup 60}Co or {sup 192}Ir sources. These data are compared with results in a water phantom and with expected values in an infinite water medium. A comparison with reported values from proton therapy and intensity-modulated radiation therapy (IMRT) is also provided. Methods: Monte Carlo simulations in Geant4 were performed using a voxelized phantom described in International Commission on Radiological Protection (ICRP) Publication 110, which reproduces masses and shapes frommore » an adult reference man defined in ICRP Publication 89. Point sources of {sup 60}Co or {sup 192}Ir with photon energy spectra corresponding to those exiting their capsules were placed in the center of the prostate, and equivalent doses per clinical absorbed dose in this target organ were obtained in several radiosensitive organs. Values were corrected to account for clinical circumstances with the source located at various positions with differing dwell times throughout the prostate. This was repeated for a homogeneous water phantom. Results: For the nearest organs considered (bladder, rectum, testes, small intestine, and colon), equivalent doses given by {sup 60}Co source were smaller (8%-19%) than from {sup 192}Ir. However, as the distance increases, the more penetrating gamma rays produced by {sup 60}Co deliver higher organ equivalent doses. The overall result is that effective dose per clinical absorbed dose from a {sup 60}Co source (11.1 mSv/Gy) is lower than from a {sup 192}Ir source (13.2 mSv/Gy). On the other hand, equivalent doses were the same in the tissue and the homogeneous water phantom for those soft tissues closer to the prostate than about 30 cm. As the distance increased, the differences of photoelectric effect in water and soft tissue, and appearance of other materials such as air, bone, or lungs, produced variations between both phantoms which were at most 35% in the considered organ equivalent doses. Finally, effective doses per clinical absorbed dose from IMRT and proton therapy were comparable to those from both brachytherapy sources, with brachytherapy being advantageous over external beam radiation therapy for the furthest organs. Conclusions: A database of organ equivalent doses when applying HDR brachytherapy to the prostate with either {sup 60}Co or {sup 192}Ir is provided. According to physical considerations, {sup 192}Ir is dosimetrically advantageous over {sup 60}Co sources at large distances, but not in the closest organs. Damage to distant healthy organs per clinical absorbed dose is lower with brachytherapy than with IMRT or protons, although the overall effective dose per Gy given to the prostate seems very similar. Given that there are several possible fractionation schemes, which result in different total amounts of therapeutic absorbed dose, advantage of a radiation treatment (according to equivalent dose to healthy organs) is treatment and facility dependent.« less

Development of transrectal diffuse optical tomography combined with 3D-transrectal ultrasound imaging to monitor the photocoagulation front during interstitial photothermal therapy of primary focal prostate cancer

NASA Astrophysics Data System (ADS)

He, Jie; Weersink, Robert; Veilleux, Israel; Mayo, Kenwrick; Zhang, Anqi; Piao, Daqing; Alam, Adeel; Trachtenberg, John; Wilson, Brian C.

2013-03-01

Interstitial near-infrared laser thermal therapy (LITT) is currently undergoing clinical trials as an alternative to watchful waiting or radical surgery in patients with low-risk focal prostate cancer. Currently, we use magnetic resonance image (MRI)-based thermography to monitor treatment delivery and determine indirectly the completeness of the target tissue destruction while avoiding damage to adjacent normal tissues, particularly the rectal wall. However, incomplete tumor destruction has occurred in a significant fraction of patients due to premature termination of treatment, since the photocoagulation zone is not directly observed. Hence, we are developing transrectal diffuse optical tomography (TRDOT), in combination with transrectal 3D ultrasound (3D-TRUS), to address his limitation. This is based on the large changes in optical scattering expected upon tissue coagulation. Here, we present forward simulations of a growing coagulated lesion with optical scattering contrast, using an established finite element analysis software platform (NIRFAST). The simulations were validated in tissue-simulating phantoms, with measurements acquired by a state-of-the-art continuous wave (CW) TRDOT system and a recently assembled bench-top CW-DOT system, with specific source-detector configurations. Two image reconstruction schemes were investigated and evaluated, specifically for the accurate delineation of the posterior boundary of the coagulation zone as the critical parameter for treatment guidance in this clinical application.

Model-based feasibility assessment and evaluation of prostate hyperthermia with a commercial MR-guided endorectal HIFU ablation array

NASA Astrophysics Data System (ADS)

Salgaonkar, Vasant A.; Prakash, Punit; Rieke, Viola; Ozhinsky, Eugene; Plata, Juan; Kurhanewicz, John; Hsu, I.-C. Joe; Diederich, Chris J.

2017-03-01

Here, operational modifications to a commercial MR-guided ultrasound phased array designed for prostate ablation (part of ExAblate 2100, InSightec Ltd) are presented for the delivery of protracted mild (40 - 45°C) hyperthermia to large contiguous target volumes in the prostate. This high-intensity focused ultrasound phased array is already in clinical trials for prostate ablation, and can be potentially fast-tracked for clinical hyperthermia treatments. As a part of this preliminary feasibility study, patient-specific numerical simulations were performed using Pennes bioheat model and acoustic field calculations were conducted using the rectangular radiator method for the ExAblate prostate array (2.3 MHz, 2.3×4.0 cm2, ˜1000 channels). Thermal solutions were computed using 3D finite element methods (FEM) implemented using Comsol Multiphysics (Comsol Inc). The patient-specific geometries were created through manual segmentation of anatomical structures from representative patient MRIs and 3D rendering (Mimics 15.01, Materialise) and generation of finite element meshes (3-Matic 7.01, Materialise). Array beamforming was employed and acoustic fields were synthesized (Matlab 2010a, MathWorks) to deliver protracted continuous wave hyperthermia to focal prostate cancer targets identified in the patient-specific models. Constraints on power densities, sonication durations and switching speeds imposed by ExAblate hardware and software were incorporated in the models. Sonication strategies explored during modeling were implemented on the ExAblate prostate array and preliminary experiments were conducted in tissue mimicking phantoms under MR temperature monitoring at 3 T (GE Discovery MR750W). Therapeutic temperatures (40 - 45 °C) could be established conformably in focal cancer volumes in a single prostate quadrant using focused heating patterns and hemi-gland heating was possible using diffused heating patterns (iso-phase or diverging). T>41 °C was calculated in 13-23 cm3 volumes for sonications with planar or diverging beam patterns at 0.9-1.2 W/cm2, in 1.5-4 cm3 volumes for simultaneous multi-point focus beam patterns at 2 - 3.4 W/cm2, and in ˜6.0 cm3 for curvilinear (cylindrical) beam patterns at 0.75 W/cm2. Patient-specific models also revealed that treatable volume sizes may be limited from pubic bone heating, especially if the pubic bone is within 15 mm from the prostate. Parametric studies also showed therapeutic heating was possible within power constraints of the phased array for a range of perfusion values (0.5 - 8 kg/m3/s), rectal cooling (22 - 35 °C) and sonication duty cycles (80% - 90%). Focused (simultaneous 4-point, cylindrical) and diffused (iso-phase, cylindrically diverging) phasing patterns investigated during modeling were successfully implemented on the ExAblate prostate array produced 4-12 °C temperature rises during protracted heating of phantom experiments (˜0.86 W/cm2, 15 min).

Numerical simulation of pressure fluctuation in 1000MW Francis turbine under small opening condition

NASA Astrophysics Data System (ADS)

Gong, R. Z.; Wang, H. G.; Yao, Y.; Shu, L. F.; Huang, Y. J.

2012-11-01

In order to study the cause of abnormal vibration in large Francis turbine under small opening condition, CFD method was adopted to analyze the flow filed and pressure fluctuation. Numerical simulation was performed on the commercial CFD code Ansys FLUENT 12, using DES method. After an effective validation of the computation result, the flow behaviour of internal flow field under small opening condition is analyzed. Pressure fluctuation in different working mode is obtained by unsteady CFD simulation, and results is compared to study its change. Radial force fluctuation is also analyzed. The result shows that the unstable flow under small opening condition leads to an increase of turbine instability in reverse pump mode, and is one possible reason of the abnormal oscillation.

Prevalence of renal insufficiency in elderly cancer patients in a tertiary cancer center

PubMed Central

Pontes, Lucíola de Barros; Antunes, Yuri Philippe Pimentel Vieira; Bugano, Diogo Diniz Gomes; Karnakis, Theodora; del Giglio, Auro; Kaliks, Rafael Aliosha

2014-01-01

Objective To estimate the prevalence of abnormal glomerular filtration rate in elderly patients with solid tumors. Methods A retrospective study with patients aged >65 years diagnosed with solid tumors between January 2007 and December 2011 in a cancer center. The following data were collected: sex, age, serum creatinine at the time of diagnosis and type of tumor. Renal function was calculated using abbreviated Modification of Diet in Renal Disease (MDRD) formulae and then staged in accordance with the clinical practice guidelines published by the Working Group of the National Kidney Foundation. Results A total of 666 patients were included and 60% were male. The median age was 74.2 years (range: 65 to 99 years). The most prevalent diagnosis in the study population were colorectal (24%), prostate (20%), breast (16%) and lung cancer (16%). The prevalence of elevated serum creatinine (>1.0mg/dL) was 30%. However, when patients were assessed using abbreviated MDRD formulae, 66% had abnormal renal function, stratified as follows: 45% with stage 2, 18% with stage 3, 3% with stage 4 and 0.3% with stage 5. Conclusion To the best of our knowledge, this was the first study to estimate the frequency of renal insufficiency in elderly cancer patients in Brazil. The prevalence of abnormal renal function among our cohort was high. As suspected, the absolute creatinine level does underestimate renal function impairment and should not be used as predictor of chemotherapy metabolism, excretion and consequent toxicity. PMID:25295449

Effect of bladder filling on doses to prostate and organs at risk: a treatment planning study

PubMed Central

Liu, Mitchell; Kristensen, Sarah; Gelowitz, Gerald; Berthelet, Eric

2007-01-01

In the present study, we aimed to evaluate effects of bladder filling on dose–volume distributions for bladder, rectum, planning target volume (PTV), and prostate in radiation therapy of prostate cancer. Patients (n=21) were scanned with a full bladder, and after 1 hour, having been allowed to void, with an empty bladder. Radiotherapy plans were generated using a four‐field box technique and dose of 70 Gy in 35 fractions. First, plans obtained for full‐ and empty‐bladder scans were compared. Second, situations in which a patient was planned on full bladder but was treated on empty bladder, and vice versa, were simulated, assuming that patients were aligned to external tattoos. Doses to the prostate [equivalent uniform dose (EUD)], bladder and rectum [effective dose (Deff)], and normal tissue complication probability (NTCP) were compared. Dose to the small bowel was examined. Mean bladder volume was 354.3 cm3 when full and 118.2 cm3 when empty. Median prostate EUD was 70 Gy for plans based on full‐ and empty‐bladder scans alike. The median rectal Deff was 55.6 Gy for full‐bladder anatomy and 56.8 Gy for empty‐bladder anatomy, and the corresponding bladder Deff was 29.0 Gy and 49.3 Gy respectively. In 1 patient, part of the small bowel (7.5 cm3) received more than 50 Gy with full‐bladder anatomy, and in 6 patients, part (2.5 cm3−30 cm3) received more than 50 Gy with empty‐bladder anatomy. Bladder filling had no significant impact on prostate EUD or rectal Deff. A minimal volume of the small bowel received more than 50 Gy in both groups, which is below dose tolerance. The bladder Deff was higher with empty‐bladder anatomy; however, the predicted complication rates were clinically insignificant. When the multileaf collimator pattern was applied in reverse, substantial underdosing of the planning target volume (PTV) was observed, particularly for patients with prostate shifts in excess of 0.5 cm in any one direction. However, the prostate shifts showed no correlation with bladder filling, and therefore the PTV underdosing also cannot be related to bladder filling. For some patients, bladder dose–volume constraints were not fulfilled in the worst‐case scenario—that is, when a patient planned with full bladder consistently arrived for treatment with an empty bladder. PACS numbers: 87.53.‐j, 87.53.Kn, 87.53.Tf PMID:17592448

Mimicry of Appendicitis Symptomatology in Congenital Anomalies and Diseases of the Genitourinary System and Pregnancy

PubMed Central

Dalpiaz, Amanda; Gandhi, Jason; Smith, Noel L.; Dagur, Gautam; Schwamb, Richard; Weissbart, Steven J.; Khan, Sardar Ali

2017-01-01

Introduction Appendicitis is a prevailing cause of acute abdomen, but is often difficult to diagnose due to its wide range of symptoms, anatomical variations, and developmental abnormalities. Urological disorders of the genitourinary tract may be closely related to appendicitis due to the close proximity of the appendix to the genitourinary tract. This review provides a summary of the urological complications and simulations of appendicitis. Both typical and urological symptoms of appendicitis are discussed, as well as recommended diagnostic and treatment methods. Methods Medline searches were conducted via PubMed in order to incorporate data from the recent and early literature. Results Urological manifestations of appendicitis affect the adrenal glands, kidney, retroperitoneum, ureter, bladder, prostate, scrotum, and penis. Appendicitis in pregnancy is difficult to diagnose due to variations in appendiceal position and trimester-specific symptoms. Ultrasound, CT, and MRI are used in diagnosis of appendicitis and its complications. Treatment of appendicitis may be done via open appendectomy or laparoscopic appendectomy. In some cases, other surgeries are required to treat urological complications, though surgery may be avoided completely in other cases. Conclusion Clinical presentation and complications of appendicitis vary among patients, especially when the genitourinary tract is involved. Appendicitis may mimic urological disorders and vice versa. Awareness of differential diagnosis and proper diagnostic techniques is important in preventing delayed diagnosis and possible complications. MRI is recommended for diagnosis of pregnant patients. Ultrasound is preferred in patients exhibiting typical symptoms. PMID:28413377

(31) P MR spectroscopic imaging combined with (1) H MR spectroscopic imaging in the human prostate using a double tuned endorectal coil at 7T.

PubMed

Luttje, Mariska P; Italiaander, Michel G M; Arteaga de Castro, Catalina S; van der Kemp, Wybe J M; Luijten, Peter R; van Vulpen, Marco; van der Heide, Uulke A; Klomp, Dennis W J

2014-12-01

Improved diagnostic sensitivity could be obtained in cancer detection and staging when individual compounds of the choline pool can be detected. Therefore, a novel coil design is proposed, providing the ability to acquire both (1) H and (31) P magnetic resonance spectroscopic imaging (MRSI) in patients with prostate cancer. A two-element (1) H/(31) P endorectal coil was designed by adjusting a commercially available 3T endorectal coil. The two-element coil setup was interfaced as a transceiver to a whole body 7T MR scanner. Simulations and phantom measurements were performed to compare the efficiency of the coil. (1) H MRSI and (31) P MRSI were acquired in vivo in prostate cancer patients. The efficiency of the (1) H/(31) P coil is comparable to the dual channel (1) H coil previously published. Individually distinguishable phospholipid metabolites in the in vivo (31) P spectra were: phosphoethanolamine, phosphocholine, phosphate, glycerophosphoethanolamine, glycerophosphocholine, phosphocreatine, and adenosine triposphate. (1) H MRSI was performed within the same scan session, visualizing choline, polyamines, creatine, and citrate. (1) H MRSI and (31) P MRSI can be acquired in the human prostate at 7T within the same scan session using an endorectal coil matched and tuned for (1) H (quadrature) and (31) P (linear) without the need of cable traps and with negligible efficiency losses in the (1) H and (31) P channel. © 2013 Wiley Periodicals, Inc.

MRI micturating urethrography for improved urethral delineation in prostate radiotherapy planning: a case study

NASA Astrophysics Data System (ADS)

Rai, Robba; Sidhom, Mark; Lim, Karen; Ohanessian, Lucy; Liney, Gary P.

2017-04-01

Stereotactic ablative body radiotherapy is used in prostate cancer to deliver a high dose of radiation to the tumour over a small number of treatments. This involves the simulation of the patient using both CT and MRI. Current practice is to insert an indwelling catheter (IDC) during CT to assist with visualisation of the urethra and subsequently minimise dose to this highly critical structure. However, this procedure is invasive and has an associated risk of infection. This is a case study, which demonstrates our initial experience of using a real-time non-invasive MRI technique to replace the use of IDC for prostate cancer patients. The patient was scanned on a dedicated 3T MRI and was instructed to micturate in their own time whereupon a sagittal T2 weighted HASTE sequence was acquired every 5 s. This was subsequently followed by T2 weighted axial imaging at the level of mid prostate to provide improved urethral definition. Acquired images showed bladder voidance in real-time and an increase in signal intensity in the proximal urethra post voiding allowing for delineation of the urethra. The dimension and shape of the proximal urethra was well visualised and accumulation time of urine in the urethra was sufficient to enable optimum timing of the scanning technique. We have presented for the first time a micturating urethography technique using MRI, which has allowed us to visualise the urethra without contrast and with minimal invasiveness to the patient.

Poster - 47: A parametrized prediction model of rectal toxicity in focal SBRT of low risk prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stevens, Todd; Bauman, Glenn

There has been a recent trend towards watchful waiting in place of intervention for early stage prostate cancer (CaP). However, this approach can allow for disease progression, and subsequent whole-gland therapies such as prostatectomy and whole gland irradiation can result in functional deficits or rectal toxicities or both. A controversial alternative approach for this patient cohort is the use of focal therapy, where the treatment is focussed on an identified dominant index lesion (DIL). This work aims to investigate the treatment parameters for focal SBRT of the prostate under which clinically acceptable rectal NTCP levels can be achieved. For eachmore » of 25 low risk CaP patients, a hypothetical 2 cc DIL was modeled in the right-posterior quadrant of the prostate, and was used to build a PTV as the target for SBRT simulation. An SBRT prescriptions of 41 Gy and 37 Gy in 5 fractions were chosen, corresponding to the boost levels used in previous CaP dose escalation studies. DVH data were exported and used to calculate rectal NTCP values based on the Lyman-Kutcher-Burman (LKB) model using the QUANTEC reccommended model parameters. Rectal NTCP dependence on DIL-to-rectum separation, dose level, and DIL volume were investigated. The final goal of this ongoing work is to create a map of the maximum allowable prescription dose for a given patient geometry that achieves a clinically acceptable rectal NTCP level.« less

99m Tc-MIP-1404-SPECT/CT for the detection of PSMA-positive lesions in 225 patients with biochemical recurrence of prostate cancer.

PubMed

Schmidkonz, Christian; Hollweg, Claudia; Beck, Michael; Reinfelder, Julia; Goetz, Theresa I; Sanders, James C; Schmidt, Daniela; Prante, Olaf; Bäuerle, Tobias; Cavallaro, Alexander; Uder, Michael; Wullich, Bernd; Goebell, Peter; Kuwert, Torsten; Ritt, Philipp

2018-01-01

99m Tc-MIP-1404 (Progenics Pharmaceuticals, Inc., New York, NY) is a novel, SPECT-compatible 99m Tc-labeled PSMA inhibitor for the detection of prostate cancer. We present results of its clinical use in a cohort of 225 men with histologically confirmed prostate cancer referred for workup of biochemical relapse. From April 2013 to April 2017, 99m Tc-MIP1404-scintigraphy was performed in 225 patients for workup of PSA biochemical relapse of prostate cancer. Whole-body planar and SPECT/CT images of the lower abdomen and thorax were obtained 3-4 h p.i. of 710 ± 64 MBq 99m Tc-MIP-1404. Images were visually analyzed for presence and location of abnormal uptake. In addition, quantitative analysis of the SPECT/CT data was carried out on a subset of 125 patients. Follow-up reports of subsequent therapeutic interventions were available for 59% (139) of all patients. Tracer-positive lesions were detected in 77% (174/225) of all patients. Detections occurred at the area of local recurrence in the prostate in 25% of patients (or a total of 56), with metastases in lymph nodes in 47% (105), bone in 27% (60), lung in 5% (12), and other locations in 2% (4) of patients. Detection rates were 90% at PSA levels ≥2 ng/mL and 54% below that threshold. Lesional SUVmax values were, on average, 32.2 ± 29.6 (0.8-142.2), and tumor-to-normal ratios 146.6 ± 160.5 (1.9-1482.4). The PSA level correlated significantly with total uptake of MIP-1404 in tumors (P < 0.001). Furthermore, total tumor uptake was significantly higher in patients with Gleason scores ≥8 compared to those with Gleason scores ≤7 (P < 0.05). In patients with androgen deprivation therapy, the detection rate was significantly higher compared to patients without androgen deprivation therapy (86% vs 71%, P < 0.001). Based on 99m Tc-MIP-1404-imaging and other information, an interdisciplinary tumor board review recommended changes to treatment plans in 74% (104/139) of those patients for whom the necessary documentation was available. SPECT/CT with 99m Tc-labeled MIP-1404 has a high probability in detecting PSMA-positive lesions in patients with elevated PSA. Statistical analysis disclosed significant relationship between quantitative 99m Tc-MIP-1404 uptake, PSA level, and Gleason score. © 2017 Wiley Periodicals, Inc.

Dosimetry Modeling for Focal Low-Dose-Rate Prostate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Qaisieh, Bashar; Mason, Josh, E-mail: joshua.mason@nhs.net; Bownes, Peter

2015-07-15

Purpose: Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA). Methods and Materials: Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focalmore » (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations. Results: WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm{sup 3} was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types. Conclusions: Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a notable reduction to organs at risk. Treating smaller targets makes seed positioning more critical.« less

Cabazitaxel Plus Prednisone With Octreotide For Castration-Resistant Prostate Cancer (CRPC) Previously Treated With Docetaxel

ClinicalTrials.gov

2014-11-21

Diarrhea; Hormone-resistant Prostate Cancer; Recurrent Prostate Cancer; Stage I Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage IV Prostate Cancer

Improving PET spatial resolution and detectability for prostate cancer imaging

NASA Astrophysics Data System (ADS)

Bal, H.; Guerin, L.; Casey, M. E.; Conti, M.; Eriksson, L.; Michel, C.; Fanti, S.; Pettinato, C.; Adler, S.; Choyke, P.

2014-08-01

Prostate cancer, one of the most common forms of cancer among men, can benefit from recent improvements in positron emission tomography (PET) technology. In particular, better spatial resolution, lower noise and higher detectability of small lesions could be greatly beneficial for early diagnosis and could provide a strong support for guiding biopsy and surgery. In this article, the impact of improved PET instrumentation with superior spatial resolution and high sensitivity are discussed, together with the latest development in PET technology: resolution recovery and time-of-flight reconstruction. Using simulated cancer lesions, inserted in clinical PET images obtained with conventional protocols, we show that visual identification of the lesions and detectability via numerical observers can already be improved using state of the art PET reconstruction methods. This was achieved using both resolution recovery and time-of-flight reconstruction, and a high resolution image with 2 mm pixel size. Channelized Hotelling numerical observers showed an increase in the area under the LROC curve from 0.52 to 0.58. In addition, a relationship between the simulated input activity and the area under the LROC curve showed that the minimum detectable activity was reduced by more than 23%.

Comparison of Timed Automata with Discrete Event Simulation for Modeling of Biomarker-Based Treatment Decisions: An Illustration for Metastatic Castration-Resistant Prostate Cancer.

PubMed

Degeling, Koen; Schivo, Stefano; Mehra, Niven; Koffijberg, Hendrik; Langerak, Rom; de Bono, Johann S; IJzerman, Maarten J

2017-12-01

With the advent of personalized medicine, the field of health economic modeling is being challenged and the use of patient-level dynamic modeling techniques might be required. To illustrate the usability of two such techniques, timed automata (TA) and discrete event simulation (DES), for modeling personalized treatment decisions. An early health technology assessment on the use of circulating tumor cells, compared with prostate-specific antigen and bone scintigraphy, to inform treatment decisions in metastatic castration-resistant prostate cancer was performed. Both modeling techniques were assessed quantitatively, in terms of intermediate outcomes (e.g., overtreatment) and health economic outcomes (e.g., net monetary benefit). Qualitatively, among others, model structure, agent interactions, data management (i.e., importing and exporting data), and model transparency were assessed. Both models yielded realistic and similar intermediate and health economic outcomes. Overtreatment was reduced by 6.99 and 7.02 weeks by applying circulating tumor cell as a response marker at a net monetary benefit of -€1033 and -€1104 for the TA model and the DES model, respectively. Software-specific differences were observed regarding data management features and the support for statistical distributions, which were considered better for the DES software. Regarding method-specific differences, interactions were modeled more straightforward using TA, benefiting from its compositional model structure. Both techniques prove suitable for modeling personalized treatment decisions, although DES would be preferred given the current software-specific limitations of TA. When these limitations are resolved, TA would be an interesting modeling alternative if interactions are key or its compositional structure is useful to manage multi-agent complex problems. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Correlations between contouring similarity metrics and simulated treatment outcome for prostate radiotherapy

NASA Astrophysics Data System (ADS)

Roach, D.; Jameson, M. G.; Dowling, J. A.; Ebert, M. A.; Greer, P. B.; Kennedy, A. M.; Watt, S.; Holloway, L. C.

2018-02-01

Many similarity metrics exist for inter-observer contouring variation studies, however no correlation between metric choice and prostate cancer radiotherapy dosimetry has been explored. These correlations were investigated in this study. Two separate trials were undertaken, the first a thirty-five patient cohort with three observers, the second a five patient dataset with ten observers. Clinical and planning target volumes (CTV and PTV), rectum, and bladder were independently contoured by all observers in each trial. Structures were contoured on T2-weighted MRI and transferred onto CT following rigid registration for treatment planning in the first trial. Structures were contoured directly on CT in the second trial. STAPLE and majority voting volumes were generated as reference gold standard volumes for each structure for the two trials respectively. VMAT treatment plans (78 Gy to PTV) were simulated for observer and gold standard volumes, and dosimetry assessed using multiple radiobiological metrics. Correlations between contouring similarity metrics and dosimetry were calculated using Spearman’s rank correlation coefficient. No correlations were observed between contouring similarity metrics and dosimetry for CTV within either trial. Volume similarity correlated most strongly with radiobiological metrics for PTV in both trials, including TCPPoisson (ρ  =  0.57, 0.65), TCPLogit (ρ  =  0.39, 0.62), and EUD (ρ  =  0.43, 0.61) for each respective trial. Rectum and bladder metric correlations displayed no consistency for the two trials. PTV volume similarity was found to significantly correlate with rectum normal tissue complication probability (ρ  =  0.33, 0.48). Minimal to no correlations with dosimetry were observed for overlap or boundary contouring metrics. Future inter-observer contouring variation studies for prostate cancer should incorporate volume similarity to provide additional insights into dosimetry during analysis.

Dosimetric verification of IMRT treatment planning using Monte Carlo simulations for prostate cancer

NASA Astrophysics Data System (ADS)

Yang, J.; Li, J.; Chen, L.; Price, R.; McNeeley, S.; Qin, L.; Wang, L.; Xiong, W.; Ma, C.-M.

2005-03-01

The purpose of this work is to investigate the accuracy of dose calculation of a commercial treatment planning system (Corvus, Normos Corp., Sewickley, PA). In this study, 30 prostate intensity-modulated radiotherapy (IMRT) treatment plans from the commercial treatment planning system were recalculated using the Monte Carlo method. Dose-volume histograms and isodose distributions were compared. Other quantities such as minimum dose to the target (Dmin), the dose received by 98% of the target volume (D98), dose at the isocentre (Diso), mean target dose (Dmean) and the maximum critical structure dose (Dmax) were also evaluated based on our clinical criteria. For coplanar plans, the dose differences between Monte Carlo and the commercial treatment planning system with and without heterogeneity correction were not significant. The differences in the isocentre dose between the commercial treatment planning system and Monte Carlo simulations were less than 3% for all coplanar cases. The differences on D98 were less than 2% on average. The differences in the mean dose to the target between the commercial system and Monte Carlo results were within 3%. The differences in the maximum bladder dose were within 3% for most cases. The maximum dose differences for the rectum were less than 4% for all the cases. For non-coplanar plans, the difference in the minimum target dose between the treatment planning system and Monte Carlo calculations was up to 9% if the heterogeneity correction was not applied in Corvus. This was caused by the excessive attenuation of the non-coplanar beams by the femurs. When the heterogeneity correction was applied in Corvus, the differences were reduced significantly. These results suggest that heterogeneity correction should be used in dose calculation for prostate cancer with non-coplanar beam arrangements.

High-Intensity Focused Ultrasound in Treating Participants With Intermediate and High-risk Prostate Cancer

ClinicalTrials.gov

2018-06-13

Stage I Prostate Cancer AJCC v8; Stage II Prostate Cancer AJCC v8; Stage IIA Prostate Cancer AJCC v8; Stage IIB Prostate Cancer AJCC v8; Stage IIC Prostate Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage IIIA Prostate Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8; Stage IIIC Prostate Cancer AJCC v8

Racial differences in the relationship between clinical prostatitis, presence of inflammation in benign prostate and subsequent risk of prostate cancer.

PubMed

Rybicki, B A; Kryvenko, O N; Wang, Y; Jankowski, M; Trudeau, S; Chitale, D A; Gupta, N S; Rundle, A; Tang, D

2016-06-01

Epidemiologic studies, primarily done in white men, suggest that a history of clinically-diagnosed prostatitis increases prostate cancer risk, but that histological prostate inflammation decreases risk. The relationship between a clinical history of prostatitis and histologic inflammation in terms of how these two manifestations of prostatic inflammation jointly contribute to prostate cancer risk and whether racial differences exist in this relationship is uncertain. Using a nested design within a cohort of men with benign prostate tissue specimens, we analyzed the data on both clinically-diagnosed prostatitis (NIH categories I-III) and histological inflammation in 574 prostate cancer case-control pairs (345 white, 229 African American). Clinical prostatitis was not associated with increased prostate cancer risk in the full sample, but showed a suggestive inverse association with prostate cancer in African Americans (odds ratio (OR)=0.47; 95% confidence interval (CI)=0.27-0.81). In whites, clinical prostatitis increased risk by 40%, but was only associated with a significant increased prostate cancer risk in the absence of evidence of histological inflammation (OR=3.56; 95% CI=1.15-10.99). Moreover, PSA velocity (P=0.008) and frequency of PSA testing (P=0.003) were significant modifiers of risk. Clinical prostatitis increased risk of prostate cancer almost three-fold (OR=2.97; 95% CI=1.40-6.30) in white men with low PSA velocity and about twofold in white men with more frequent PSA testing (OR=1.91; 95% CI=1.09-3.35). In our cohort of men with benign prostate specimens, race, and histological inflammation were important cofactors in the relationship between clinical prostatitis and prostate cancer. Clinical prostatitis was associated with a slightly decreased risk for prostate cancer in African American men. In white men, the relationship between clinical prostatitis and prostate cancer risk was modified by histological prostatic inflammation, PSA velocity, and frequency of PSA testing-suggesting a complex interplay between these indications of prostatic inflammation and prostate cancer detection.

Racial differences in the relationship between clinical prostatitis, presence of inflammation in benign prostate and subsequent risk of prostate cancer

PubMed Central

Rybicki, BA; Kryvenko, ON; Wang, Y; Jankowski, M; Trudeau, S; Chitale, DA; Gupta, NS; Rundle, A; Tang, D

2016-01-01

BACKGROUND Epidemiologic studies, primarily done in white men, suggest that a history of clinically-diagnosed prostatitis increases prostate cancer risk, but that histological prostate inflammation decreases risk. The relationship between a clinical history of prostatitis and histologic inflammation in terms of how these two manifestations of prostatic inflammation jointly contribute to prostate cancer risk and whether racial differences exist in this relationship is uncertain. METHODS Using a nested design within a cohort of men with benign prostate tissue specimens, we analyzed the data on both clinically-diagnosed prostatitis (NIH categories I–III) and histological inflammation in 574 prostate cancer case-control pairs (345 white, 229 African American). RESULTS Clinical prostatitis was not associated with increased prostate cancer risk in the full sample, but showed a suggestive inverse association with prostate cancer in African Americans (odds ratio (OR) = 0.47; 95% confidence interval (CI) = 0.27–0.81). In whites, clinical prostatitis increased risk by 40%, but was only associated with a significant increased prostate cancer risk in the absence of evidence of histological inflammation (OR = 3.56; 95% CI = 1.15–10.99). Moreover, PSA velocity (P = 0.008) and frequency of PSA testing (P = 0.003) were significant modifiers of risk. Clinical prostatitis increased risk of prostate cancer almost three-fold (OR = 2.97; 95% CI = 1.40–6.30) in white men with low PSA velocity and about twofold in white men with more frequent PSA testing (OR = 1.91; 95% CI = 1.09–3.35). CONCLUSIONS In our cohort of men with benign prostate specimens, race, and histological inflammation were important cofactors in the relationship between clinical prostatitis and prostate cancer. Clinical prostatitis was associated with a slightly decreased risk for prostate cancer in African American men. In white men, the relationship between clinical prostatitis and prostate cancer risk was modified by histological prostatic inflammation, PSA velocity, and frequency of PSA testing—suggesting a complex interplay between these indications of prostatic inflammation and prostate cancer detection. PMID:26620738

Observation Versus Initial Treatment for Men With Localized, Low-Risk Prostate Cancer A Cost-Effectiveness Analysis

PubMed Central

Hayes, Julia H.; Ollendorf, Daniel A.; Pearson, Steven D.; Barry, Michael J.; Kantoff, Philip W.; Lee, Pablo A.; McMahon, Pamela M.

2015-01-01

Background Observation is underused among men with localized, low-risk prostate cancer. Objective To assess the costs and benefits of observation versus initial treatment. Design Decision analysis simulating treatment or observation. Data Sources Medicare schedules, published literature. Target Population Men ages 65 and 75 years with newly diagnosed low-risk prostate cancer (prostate-specific antigen level <10 μg/L, stage ≤T2a, Gleason score ≤3+3). Time Horizon Lifetime. Perspective Societal. Intervention Treatment (brachytherapy, intensity-modulated radiation therapy, or radical prostatectomy) or observation (active surveillance [AS] or watchful waiting [WW]). Outcome Measures Quality-adjusted life expectancy, costs. Results of Base-Case Analysis Observation was more effective and less costly than initial treatment. Compared with AS, WW provided 2 additional months of quality-adjusted life expectancy (9.02 vs. 8.85 years) at a savings of $15 374 ($24 520 vs. $39 894) in men aged 65 years and 2 additional months (6.14 vs. 5.98 years) at a savings of $11 746 ($18 302 vs. $30 048) in men aged 75 years. Brachytherapy was the most effective and least expensive initial treatment. Results of Sensitivity Analysis Treatment became more effective than observation when it led to more dramatic reductions in prostate cancer death (hazard ratio, 0.47 vs. WW and 0.64 vs. AS). Active surveillance became as effective as WW in men aged 65 years when the probability of progressing to treatment on AS decreased below 63% or when the quality of life with AS versus WW was 4% higher in men aged 65 years or 1% higher in men aged 75 years. Watchful waiting remained least expensive in all analyses. Limitation Results depend on outcomes reported in the published literature, which is limited. Conclusion Among these men, observation is more effective and costs less than initial treatment, and WW is most effective and least expensive under a wide range of clinical scenarios. Primary Funding Source National Cancer Institute, U.S. Department of Defense, Prostate Cancer Foundation, and Blue Shield of California Foundation. PMID:23778902

WE-AB-207B-03: A Computational Methodology for Determination of CTV-To-PTV Margins with Inter Fractional Shape Variations Based On a Statistical Point Distribution Model for Prostate Cancer Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shibayama, Y; Umezu, Y; Nakamura, Y

2016-06-15

Purpose: Our assumption was that interfractional shape variations of target volumes could not be negligible for determination of clinical target volume (CTV)-to-planning target volume (PTV) margins. The aim of this study was to investigate this assumption as a simulation study by developing a computational framework of CTV-to-PTV margins with taking the interfractional shape variations into account based on point distribution model (PDM) Methods: The systematic and random errors for interfractional shape variations and translations of target volumes were evaluated for four types of CTV regions (only a prostate, a prostate plus proximal 1-cm seminal vesicles, a prostate plus proximal 2-cmmore » seminal vesicles, and a prostate plus whole seminal vesicles). The CTV regions were delineated depending on prostate cancer risk groups on planning computed tomography (CT) and cone beam CT (CBCT) images of 73 fractions of 10 patients. The random and systematic errors for shape variations of CTV regions were derived from PDMs of CTV surfaces for all fractions of each patient. Systematic errors of shape variations of CTV regions were derived by comparing PDMs between planning CTV surfaces and average CTV surfaces. Finally, anisotropic CTV-to-PTV margins with shape variations in 6 directions (anterior, posterior, superior, inferior, right, and left) were computed by using a van Herk margin formula. Results: Differences between CTV-to-PTV margins with and without shape variations ranged from 0.7 to 1.7 mm in anterior direction, 1.0 to 2.8 mm in posterior direction, 0.8 to 2.8 mm in superior direction, 0.6 to 1.6 mm in inferior direction, 1.4 to 4.4 mm in right direction, and 1.3 to 5.2 mm in left direction. Conclusion: More than 1.0 mm additional margins were needed at least in 3 directions to guarantee CTV coverage due to shape variations. Therefore, shape variations should be taken into account for the determination of CTV-to-PTV margins.« less

SU-E-T-457: Impact of Interfractional Variations On Anterior Vs. Lateral-Field Proton Therapy of Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moteabbed, M; Trofimov, A; Sharp, G C

2015-06-15

Purpose: To investigate the effects of interfractional anatomy and setup variations on plans with anterior-oblique vs. lateral beams for prostate cancer pencil beam scanning (PBS) and passive scattered (PS) proton therapy. Methods: Six patients with low/intermediate risk prostate cancer treated with PS proton therapy at our institution were selected. All patients underwent weekly verification CT scans. Implanted fiducials were used for localization, and endorectal balloons for prostate immobilization. New PBS plans with lateral beams, as well as PBS and PS plans with anterior-oblique beams (±35 deg) were created. PBS plans used two different spot sizes: ∼10mm (large) and ∼5mm (medium)more » sigma at 25cm range and optimized as single-field-uniform-dose with ∼8% non-uniformity. No range uncertainty margins were applied in PBS plans to maximize rectal sparing. Field-specific apertures were used when planning with large spots to sharpen the penumbrae. The planned dose was recomputed on each weekly CT with fiducials aligned to the simulation CT, scaled and accumulated via deformable image registration. Results: The dose volume analysis showed that although difference between planned and accumulated dose remains negligible for plans with conventional lateral beams using both PS and PBS, this is not the case for plans with anterior beams. The target coverage in anterior plans was largely degraded due to the variations in the beam path length and the absence of range margins. The average prostate D95 was reduced by 7.5/15.9% (using PS/PBS) after accumulation for anterior plans, compared with 0/0.4% for lateral plans. The average mean dose in organs-at-risk decreased by 1% for lateral and 2% for anterior plans, similarly for PS and PBS. Spot size did not affect the dose changes. Conclusion: Prostate plans using anterior beams may undergo clinically relevant interfractional dose degradation. Corrective strategies guided by in-vivo range measurements should be studied before clinical application of this technique.« less

Bladder urothelial carcinoma extending to rectal mucosa and presenting with rectal bleeding

PubMed Central

Aneese, Andrew M; Manuballa, Vinayata; Amin, Mitual; Cappell, Mitchell S

2017-01-01

An 87-year-old-man with prostate-cancer-stage-T1c-Gleason-6 treated with radiotherapy in 1996, recurrent prostate cancer treated with leuprolide hormonal therapy in 2009, and bladder-urothelial-carcinoma in situ treated with Bacillus-Calmette-Guerin and adriamycin in 2010, presented in 2015 with painless, bright red blood per rectum coating stools daily for 5 mo. Rectal examination revealed bright red blood per rectum; and a hard, fixed, 2.5 cm × 2.5 cm mass at the normal prostate location. The hemoglobin was 7.6 g/dL (iron saturation = 8.4%, indicating iron-deficiency-anemia). Abdominopelvic-CT-angiography revealed focal wall thickening at the bladder neck; a mass containing an air cavity replacing the normal prostate; and adjacent rectal invasion. Colonoscopy demonstrated an ulcerated, oozing, multinodular, friable, 2.5 cm × 2.5 cm mass in anterior rectal wall, at the usual prostate location. Histologic and immunohistochemical analysis of colonoscopic biopsies of the mass revealed poorly-differentiated-carcinoma of urothelial origin. At visceral angiography, the right-superior-rectal-artery was embolized to achieve hemostasis. The patient subsequently developed multiple new metastases and expired 13 mo post-embolization. Comprehensive literature review revealed 16 previously reported cases of rectal involvement from bladder urothelial carcinoma, including 11 cases from direct extension and 5 cases from metastases. Patient age averaged 63.7 ± 9.6 years (all patients male). Rectal involvement was diagnosed on average 13.5 ± 11.8 mo after initial diagnosis of bladder urothelial carcinoma. Symptoms included constipation/gastrointestinal obstruction-6, weight loss-5, diarrhea-3, anorexia-3, pencil thin stools-3, tenesmus-2, anorectal pain-2, and other-5. Rectal examination in 9 patients revealed annular rectal constriction-6, and rectal mass-3. The current patient had the novel presentation of daily bright red blood per rectum coating the stools simulating hemorrhoidal bleeding; the novel mechanism of direct bladder urothelial carcinoma extension into rectal mucosa via the prostate; and the novel aforementioned colonoscopic findings underlying the clinical presentation. PMID:28690772

SU-G-JeP4-13: Continuous Intra-Fractional Monitoring of the Prostate Using Dynamic KV Collimation and Tube Current Modulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parsons, D; Robar, J; Nova Scotia Health Authority, Halifax, NS

Purpose: The focus of this work is to improve the available kV image quality for continuous intra-fraction monitoring of the prostate. This is investigated using a novel blade collimation system enabling modulated volume-of-interest (VOI) imaging of prostate fiducial markers. Methods: A four-blade dynamic kV collimator was used to track a VOI during gantry rotation. Planar image quality was investigated as a function of collimator dimension, while maintaining the same dose to isocenter, for a 22.2 cm diameter cylindrical water phantom with a 9 mm diameter bone insert. A sample prostate anatomy was defined in the planning system, including three fiducialmore » markers within the CTV. The VOI margin around each marker was set to be 2σ of the population covariance matrix characterizing prostate motion. DRRs were used to calculate the kV attenuation for each VOI as a function of angle. The optimal marker and tube current were determined using kV attenuation. Monte Carlo simulations were used to calculate the imaging dose to the phantom and MV scatter dose to the imaging panel. Results: Preliminary measurements show an increase in CNR by a factor of 1.3 with the VOI method, when decreasing from an 6×6 to 2×2 cm{sup 2} field. Attenuation calculations show a change in kV fluence at the detector by a factor of 21.6 with fiducial optimization; resultant tube current modulation increases maximum dose by a factor of 1.4 compared to no modulation. MV scatter contribution to the kV detector changes by approximately a factor of two over a complete gantry rotation. Conclusion: The dynamic collimation system allows single fiducial marker tracking at a very low dose, with reduction of scatter and improvement of image quality, compared to imaging the entire prostate. The approach is compatible with tube current modulation, which enables consistent image quality throughout the range of gantry rotation. This project was funded by Varian Medical Systems.« less

Screening for SNPs with Allele-Specific Methylation based on Next-Generation Sequencing Data.

PubMed

Hu, Bo; Ji, Yuan; Xu, Yaomin; Ting, Angela H

2013-05-01

Allele-specific methylation (ASM) has long been studied but mainly documented in the context of genomic imprinting and X chromosome inactivation. Taking advantage of the next-generation sequencing technology, we conduct a high-throughput sequencing experiment with four prostate cell lines to survey the whole genome and identify single nucleotide polymorphisms (SNPs) with ASM. A Bayesian approach is proposed to model the counts of short reads for each SNP conditional on its genotypes of multiple subjects, leading to a posterior probability of ASM. We flag SNPs with high posterior probabilities of ASM by accounting for multiple comparisons based on posterior false discovery rates. Applying the Bayesian approach to the in-house prostate cell line data, we identify 269 SNPs as candidates of ASM. A simulation study is carried out to demonstrate the quantitative performance of the proposed approach.

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

PubMed

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 <2.0 ng/mL. The case cohort comprised 150 men with a baseline prostate-specific antigen level <2.0 ng/mL, and who developed prostate cancer within 10 years. The control cohort was 300 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.

Genetic and Molecular Mechanisms in Assessing Response in Patients With Prostate Cancer Receiving Enzalutamide Therapy

ClinicalTrials.gov

2018-01-22

Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma in the Soft Tissue; Metastatic Prostatic Adenocarcinoma; Prostate Carcinoma Metastatic in the Bone; PSA Progression; Recurrent Prostate Carcinoma; Stage III Prostate Adenocarcinoma; Stage IV Prostate Adenocarcinoma

Research on burnout fault of moulded case circuit breaker based on finite element simulation

NASA Astrophysics Data System (ADS)

Xue, Yang; Chang, Shuai; Zhang, Penghe; Xu, Yinghui; Peng, Chuning; Shi, Erwei

2017-09-01

In the failure event of molded case circuit breaker, overheating of the molded case near the wiring terminal has a very important proportion. The burnout fault has become an important factor restricting the development of molded case circuit breaker. This paper uses the finite element simulation software to establish the model of molded case circuit breaker by coupling multi-physics field. This model can simulate the operation and study the law of the temperature distribution. The simulation results show that the temperature near the wiring terminal, especially the incoming side of the live wire, of the molded case circuit breaker is much higher than that of the other areas. The steady-state and transient simulation results show that the temperature at the wiring terminals is abnormally increased by increasing the contact resistance of the wiring terminals. This is consistent with the frequent occurrence of burnout of the molded case in this area. Therefore, this paper holds that the burnout failure of the molded case circuit breaker is mainly caused by the abnormal increase of the contact resistance of the wiring terminal.

MRI simulation: end-to-end testing for prostate radiation therapy using geometric pelvic MRI phantoms

NASA Astrophysics Data System (ADS)

Sun, Jidi; Dowling, Jason; Pichler, Peter; Menk, Fred; Rivest-Henault, David; Lambert, Jonathan; Parker, Joel; Arm, Jameen; Best, Leah; Martin, Jarad; Denham, James W.; Greer, Peter B.

2015-04-01

To clinically implement MRI simulation or MRI-alone treatment planning requires comprehensive end-to-end testing to ensure an accurate process. The purpose of this study was to design and build a geometric phantom simulating a human male pelvis that is suitable for both CT and MRI scanning and use it to test geometric and dosimetric aspects of MRI simulation including treatment planning and digitally reconstructed radiograph (DRR) generation. A liquid filled pelvic shaped phantom with simulated pelvic organs was scanned in a 3T MRI simulator with dedicated radiotherapy couch-top, laser bridge and pelvic coil mounts. A second phantom with the same external shape but with an internal distortion grid was used to quantify the distortion of the MR image. Both phantoms were also CT scanned as the gold-standard for both geometry and dosimetry. Deformable image registration was used to quantify the MR distortion. Dose comparison was made using a seven-field IMRT plan developed on the CT scan with the fluences copied to the MR image and recalculated using bulk electron densities. Without correction the maximum distortion of the MR compared with the CT scan was 7.5 mm across the pelvis, while this was reduced to 2.6 and 1.7 mm by the vendor’s 2D and 3D correction algorithms, respectively. Within the locations of the internal organs of interest, the distortion was <1.5 and <1 mm with 2D and 3D correction algorithms, respectively. The dose at the prostate isocentre calculated on CT and MRI images differed by 0.01% (1.1 cGy). Positioning shifts were within 1 mm when setup was performed using MRI generated DRRs compared to setup using CT DRRs. The MRI pelvic phantom allows end-to-end testing of the MRI simulation workflow with comparison to the gold-standard CT based process. MRI simulation was found to be geometrically accurate with organ dimensions, dose distributions and DRR based setup within acceptable limits compared to CT.

Prostatic Lesions in Odontocete Cetaceans.

PubMed

Suárez-Santana, Cristian M; Sierra, Eva; Díaz-Delgado, Josue; Zucca, Daniele; de Quirós, Yara Bernaldo; Puig-Lozano, Raquel; Câmara, Nakita; De la Fuente, Jesús; de Los Monteros, Antonio Espinosa; Rivero, Miguel; Arbelo, Manuel; Fernández, Antonio

2018-05-01

The prostate is the only accessory male genital gland described in cetaceans. Although few studies describe the gross and histologic anatomy of the prostate in cetaceans, there is no information on pathological findings involving this organ. The prostate glands of 45 cetaceans, including 8 different odontocete species ( n = 44) and 1 mysticete, were evaluated. The main pathologic diagnoses were verminous prostatitis, septic prostatitis, viral prostatitis, benign prostatic hyperplasia, and prostatitis of unknown etiology. Verminous prostatitis ( n = 12) was caused by nematodes of the genus Crassicauda, and different presentations were observed. Septic prostatitis, identified in 2 cases, both involved nematode infestation and Clostridium spp coinfection. One case of viral prostatitis was identified and was associated with morbillivirus infection. In prostatitis of unknown cause ( n = 7), varying degrees of prostatic lesions, mostly chronic inflammation, were identified. Impacts at individual levels (eg, localized disease, loss of reproductive capacity) and population levels (eg, decreased reproductive success) are plausible. Our results indicate a high occurrence of prostatic lesions in free-ranging odontocetes. For this reason, the prostate should be routinely inspected and sampled during necropsy of odontocete cetaceans.

Prostate-specific antigen lowering effect of metabolic syndrome is influenced by prostate volume.

PubMed

Choi, Woo Suk; Heo, Nam Ju; Paick, Jae-Seung; Son, Hwancheol

2016-04-01

To investigate the influence of metabolic syndrome on prostate-specific antigen levels by considering prostate volume and plasma volume. We retrospectively analyzed 4111 men who underwent routine check-ups including prostate-specific antigen and transrectal ultrasonography. The definition of metabolic syndrome was based on the modified Adult Treatment Panel III criteria. Prostate-specific antigen mass density (prostate-specific antigen × plasma volume / prostate volume) was calculated for adjusting plasma volume and prostate volume. We compared prostate-specific antigen and prostate-specific antigen mass density levels of participants with metabolic syndrome (metabolic syndrome group, n = 1242) and without metabolic syndrome (non-prostate-specific antigen metabolic syndrome group, n = 2869). To evaluate the impact of metabolic syndrome on prostate-specific antigen, linear regression analysis for the natural logarithm of prostate-specific antigen was used. Patients in the metabolic syndrome group had significantly older age (P < 0.001), larger prostate volume (P < 0.001), higher plasma volume (P < 0.001) and lower mean serum prostate-specific antigen (non-metabolic syndrome group vs metabolic syndrome group; 1.22 ± 0.91 vs 1.15 ± 0.76 ng/mL, P = 0.006). Prostate-specific antigen mass density in the metabolic syndrome group was still significantly lower than that in the metabolic syndrome group (0.124 ± 0.084 vs 0.115 ± 0.071 μg/mL, P = 0.001). After adjusting for age, prostate volume and plasma volume using linear regression model, the presence of metabolic syndrome was a significant independent factor for lower prostate-specific antigen (prostate-specific antigen decrease by 4.1%, P = 0.046). Prostate-specific antigen levels in patients with metabolic syndrome seem to be lower, and this finding might be affected by the prostate volume. © 2016 The Japanese Urological Association.

The Politics of Plastics: The Making and Unmaking of Bisphenol A “Safety”

PubMed Central

2009-01-01

Bisphenol A (BPA), a synthetic chemical used in the production of plastics since the 1950s and a known endocrine disruptor, is a ubiquitous component of the material environment and human body. New research on very-low-dose exposure to BPA suggests an association with adverse health effects, including breast and prostate cancer, obesity, neurobehavioral problems, and reproductive abnormalities. These findings challenge the long-standing scientific and legal presumption of BPA's safety. The history of how BPA's safety was defined and defended provides critical insight into the questions now facing lawmakers and regulators: is BPA safe, and if not, what steps must be taken to protect the public's health? Answers to both questions involve reforms in chemical policy, with implications beyond BPA. PMID:19890158

Gastric cancer presenting with solitary gigantic pelvic metastasis.

PubMed

Zheng, Qi; Nan, Kejun; Yao, Yu

2012-07-01

Bone metastasis of gastric cancer is relatively uncommon in clinical practice. Moreover, it is all the more unusual for the primary presentation of gastric malignancy to be bone metastasis. Here, we describe a male patient who complained of pain and edema in his right lower extremity. Further assessment by computed tomography and positron emission tomography revealed an abnormally thickened gastric cardia and a giant neoplasm in the right pelvis with bone damage. Consequently, the finding of adenocarcinoma cells in pelvic and cardia biopsy specimens contributed to the diagnosis of pelvic metastasis from gastric cancer. This case report illustrates that stomach cancer has the potential, although far less than breast, prostate and lung cancers, to metastasize to bone. In addition, it highlights the peculiarity of this bone metastasis which is pelvic, solitary and huge.

Effectiveness of the combined evaluation of KLK3 genetics and free-to-total prostate specific antigen ratio for prostate cancer diagnosis.

PubMed

Zambon, Carlo-Federico; Prayer-Galetti, Tommaso; Basso, Daniela; Padoan, Andrea; Rossi, Elisa; Secco, Silvia; Pelloso, Michela; Fogar, Paola; Navaglia, Filippo; Moz, Stefania; Zattoni, Filiberto; Plebani, Mario

2012-10-01

Of serum prostate specific antigen variability 40% depends on inherited factors. We ascertained whether the knowledge of KLK3 genetics would enhance prostate specific antigen diagnostic performance in patients with clinical suspicion of prostate cancer. We studied 1,058 men who consecutively underwent prostate biopsy for clinical suspicion of prostate cancer. At histology prostate cancer was present in 401 cases and absent in 657. Serum total prostate specific antigen and the free-to-total prostate specific antigen ratio were determined. Four polymorphisms of the KLK3 gene (rs2569733, rs2739448, rs925013 and rs2735839) and 1 polymorphism of the SRD5A2 gene (rs523349) were studied. The influence of genetics on prostate specific antigen variability was evaluated by multivariate linear regression analysis. The performance of total prostate specific antigen and the free-to-total prostate specific antigen ratio alone or combined with a genetically based patient classification were defined by ROC curve analyses. For prostate cancer diagnosis the free-to-total prostate specific antigen ratio index alone (cutoff 11%) was superior to total prostate specific antigen (cutoff 4 ng/ml) and to free-to-total prostate specific antigen ratio reflex testing (positive predictive value 61%, 43% and 54%, respectively). Prostate specific antigen correlated with KLK3 genetics (rs2735839 polymorphism p = 0.001, and rs2569733, rs2739448 and rs925013 haplotype combination p = 0.003). In patients with different KLK3 genetics 2 optimal free-to-total prostate specific antigen ratio cutoffs (11% and 14.5%) were found. For free-to-total prostate specific antigen ratio values between 11% and 14.5% the prostate cancer probability ranged from 30.0% to 47.4% according to patient genetics. The free-to-total prostate specific antigen ratio is superior to total prostate specific antigen for prostate cancer diagnosis, independent of total prostate specific antigen results. Free-to-total prostate specific antigen ratio findings below 11% are positively associated with prostate cancer and those above 14.5% are negatively associated with prostate cancer, while the interpretation of those between 11% and 14.5% is improved by patient KLK3 genetic analysis. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Olaparib With or Without Cediranib in Treating Patients With Metastatic Castration-Resistant Prostate Cancer

ClinicalTrials.gov

2018-06-04

Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma With Focal Neuroendocrine Differentiation; Prostate Carcinoma Metastatic in the Bone; Prostate Small Cell Carcinoma; PSA Progression; Stage IV Prostate Adenocarcinoma AJCC v7

SU-F-T-214: Re-Thinking the Useful Clinical Beam Energy in Proton Therapy: An Opportunity for Cost Reduction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bentefour, El H; Lu, H

Purpose: We conducted a retrospective study of the useful clinical proton beam energy based on the beam range data of patients treated over the last 10 years at Massachusetts General Hospital Proton Therapy Center. Methods: Treatment field information were collected for all patients treated over the last 10 years (2005–2015) in the two gantry treatment rooms at MGH. The beam ranges for these fields were retrieved and categorized per treatment site. The 10 prostate patients that required the highest beam range (lateral fields) were selected. For these patients, anterior oblique beams (30–40 degrees) were simulated in a planning system tomore » obtain the required beam ranges including the margins for potential range uncertainties. Results: There were a total of 4033 patients, treated with combined total of 23603 fields. All treatment indications were considered with the exception of ocular tumors generally treated in a fixed beam room. For all non-prostate treatments (21811 fields), only 5 fields for 4 patients (1-pancreas, 1-lumbar chordoma, 2-spine mets) required beam range greater than 25 cm. There were 446 prostate patients (1792 fields), with the required beam range from 22.3 to 29.0 cm; 386 of them had at least one of their lateral beam range greater than 25 cm. For the 10 prostate patients with highest lateral beam ranges (26 to 29 cm), their treatment with anterior oblique beams would drop the beam ranges below 25 cm (17.3 to 18.5 cm). Conclusion: if prostate patients are treated with anterior fields only, the useful maximum beam range is reduced to 25 cm. Thus a proton therapy system with maximum beam energy of 196 MeV is sufficient to treat all tumors sites with very rare exceptions (<0.1%). Designing such PT system would reduce the cost of proton therapy for hospitals and patients and increase the accessibility to the treatment.« less

Fast GPU-based Monte Carlo simulations for LDR prostate brachytherapy.

PubMed

Bonenfant, Éric; Magnoux, Vincent; Hissoiny, Sami; Ozell, Benoît; Beaulieu, Luc; Després, Philippe

2015-07-07

The aim of this study was to evaluate the potential of bGPUMCD, a Monte Carlo algorithm executed on Graphics Processing Units (GPUs), for fast dose calculations in permanent prostate implant dosimetry. It also aimed to validate a low dose rate brachytherapy source in terms of TG-43 metrics and to use this source to compute dose distributions for permanent prostate implant in very short times. The physics of bGPUMCD was reviewed and extended to include Rayleigh scattering and fluorescence from photoelectric interactions for all materials involved. The radial and anisotropy functions were obtained for the Nucletron SelectSeed in TG-43 conditions. These functions were compared to those found in the MD Anderson Imaging and Radiation Oncology Core brachytherapy source registry which are considered the TG-43 reference values. After appropriate calibration of the source, permanent prostate implant dose distributions were calculated for four patients and compared to an already validated Geant4 algorithm. The radial function calculated from bGPUMCD showed excellent agreement (differences within 1.3%) with TG-43 accepted values. The anisotropy functions at r = 1 cm and r = 4 cm were within 2% of TG-43 values for angles over 17.5°. For permanent prostate implants, Monte Carlo-based dose distributions with a statistical uncertainty of 1% or less for the target volume were obtained in 30 s or less for 1 × 1 × 1 mm(3) calculation grids. Dosimetric indices were very similar (within 2.7%) to those obtained with a validated, independent Monte Carlo code (Geant4) performing the calculations for the same cases in a much longer time (tens of minutes to more than a hour). bGPUMCD is a promising code that lets envision the use of Monte Carlo techniques in a clinical environment, with sub-minute execution times on a standard workstation. Future work will explore the use of this code with an inverse planning method to provide a complete Monte Carlo-based planning solution.

Fast GPU-based Monte Carlo simulations for LDR prostate brachytherapy

NASA Astrophysics Data System (ADS)

Bonenfant, Éric; Magnoux, Vincent; Hissoiny, Sami; Ozell, Benoît; Beaulieu, Luc; Després, Philippe

2015-07-01

The aim of this study was to evaluate the potential of bGPUMCD, a Monte Carlo algorithm executed on Graphics Processing Units (GPUs), for fast dose calculations in permanent prostate implant dosimetry. It also aimed to validate a low dose rate brachytherapy source in terms of TG-43 metrics and to use this source to compute dose distributions for permanent prostate implant in very short times. The physics of bGPUMCD was reviewed and extended to include Rayleigh scattering and fluorescence from photoelectric interactions for all materials involved. The radial and anisotropy functions were obtained for the Nucletron SelectSeed in TG-43 conditions. These functions were compared to those found in the MD Anderson Imaging and Radiation Oncology Core brachytherapy source registry which are considered the TG-43 reference values. After appropriate calibration of the source, permanent prostate implant dose distributions were calculated for four patients and compared to an already validated Geant4 algorithm. The radial function calculated from bGPUMCD showed excellent agreement (differences within 1.3%) with TG-43 accepted values. The anisotropy functions at r = 1 cm and r = 4 cm were within 2% of TG-43 values for angles over 17.5°. For permanent prostate implants, Monte Carlo-based dose distributions with a statistical uncertainty of 1% or less for the target volume were obtained in 30 s or less for 1 × 1 × 1 mm3 calculation grids. Dosimetric indices were very similar (within 2.7%) to those obtained with a validated, independent Monte Carlo code (Geant4) performing the calculations for the same cases in a much longer time (tens of minutes to more than a hour). bGPUMCD is a promising code that lets envision the use of Monte Carlo techniques in a clinical environment, with sub-minute execution times on a standard workstation. Future work will explore the use of this code with an inverse planning method to provide a complete Monte Carlo-based planning solution.

Assessment of dosimetric impact of system specific geometric distortion in an MRI only based radiotherapy workflow for prostate

NASA Astrophysics Data System (ADS)

Gustafsson, C.; Nordström, F.; Persson, E.; Brynolfsson, J.; Olsson, L. E.

2017-04-01

Dosimetric errors in a magnetic resonance imaging (MRI) only radiotherapy workflow may be caused by system specific geometric distortion from MRI. The aim of this study was to evaluate the impact on planned dose distribution and delineated structures for prostate patients, originating from this distortion. A method was developed, in which computer tomography (CT) images were distorted using the MRI distortion field. The displacement map for an optimized MRI treatment planning sequence was measured using a dedicated phantom in a 3 T MRI system. To simulate the distortion aspects of a synthetic CT (electron density derived from MR images), the displacement map was applied to CT images, referred to as distorted CT images. A volumetric modulated arc prostate treatment plan was applied to the original CT and the distorted CT, creating a reference and a distorted CT dose distribution. By applying the inverse of the displacement map to the distorted CT dose distribution, a dose distribution in the same geometry as the original CT images was created. For 10 prostate cancer patients, the dose difference between the reference dose distribution and inverse distorted CT dose distribution was analyzed in isodose level bins. The mean magnitude of the geometric distortion was 1.97 mm for the radial distance of 200-250 mm from isocenter. The mean percentage dose differences for all isodose level bins, were  ⩽0.02% and the radiotherapy structure mean volume deviations were  <0.2%. The method developed can quantify the dosimetric effects of MRI system specific distortion in a prostate MRI only radiotherapy workflow, separated from dosimetric effects originating from synthetic CT generation. No clinically relevant dose difference or structure deformation was found when 3D distortion correction and high acquisition bandwidth was used. The method could be used for any MRI sequence together with any anatomy of interest.

Assessment of dosimetric impact of system specific geometric distortion in an MRI only based radiotherapy workflow for prostate.

PubMed

Gustafsson, C; Nordström, F; Persson, E; Brynolfsson, J; Olsson, L E

2017-04-21

Dosimetric errors in a magnetic resonance imaging (MRI) only radiotherapy workflow may be caused by system specific geometric distortion from MRI. The aim of this study was to evaluate the impact on planned dose distribution and delineated structures for prostate patients, originating from this distortion. A method was developed, in which computer tomography (CT) images were distorted using the MRI distortion field. The displacement map for an optimized MRI treatment planning sequence was measured using a dedicated phantom in a 3 T MRI system. To simulate the distortion aspects of a synthetic CT (electron density derived from MR images), the displacement map was applied to CT images, referred to as distorted CT images. A volumetric modulated arc prostate treatment plan was applied to the original CT and the distorted CT, creating a reference and a distorted CT dose distribution. By applying the inverse of the displacement map to the distorted CT dose distribution, a dose distribution in the same geometry as the original CT images was created. For 10 prostate cancer patients, the dose difference between the reference dose distribution and inverse distorted CT dose distribution was analyzed in isodose level bins. The mean magnitude of the geometric distortion was 1.97 mm for the radial distance of 200-250 mm from isocenter. The mean percentage dose differences for all isodose level bins, were  ⩽0.02% and the radiotherapy structure mean volume deviations were  <0.2%. The method developed can quantify the dosimetric effects of MRI system specific distortion in a prostate MRI only radiotherapy workflow, separated from dosimetric effects originating from synthetic CT generation. No clinically relevant dose difference or structure deformation was found when 3D distortion correction and high acquisition bandwidth was used. The method could be used for any MRI sequence together with any anatomy of interest.

Effect of using different U/S probe Standoff materials in image geometry for interventional procedures: the example of prostate

PubMed Central

Diamantopoulos, Stefanos; Butt, Saeed; Katsilieri, Zaira; Kefala, Vasiliki; Zogal, Pawel; Sakas, George; Baltas, Dimos

2011-01-01

Purpose This study investigates the distortion of geometry of catheters and anatomy in acquired U/S images, caused by utilizing various stand-off materials for covering a transrectal bi-planar ultrasound probe in HDR and LDR prostate brachytherapy, biopsy and other interventional procedures. Furthermore, an evaluation of currently established water-bath based quality assurance (QA) procedures is presented. Material and methods Image acquisitions of an ultrasound QA setup were carried out at 5 MHz and 7 MHz. The U/S probe was covered by EA 4015 Silicone Standoff kit, or UA0059 Endocavity balloon filled either with water or one of the following: 40 ml of Endosgel®, Instillagel®, Ultraschall gel or Space OAR™ gel. The differences between images were recorded. Consequently, the dosimetric impact of the observed image distortion was investigated, using a tissue equivalent ultrasound prostate phantom – Model number 053 (CIRS Inc., Norfolk, VA, USA). Results By using the EA 4015 Silicone Standoff kit in normal water with sound speed of 1525 m/s, a 3 mm needle shift was observed. The expansion of objects appeared in radial direction. The shift deforms also the PTV (prostate in our case) and other organs at risk (OARs) in the same way leading to overestimation of volume and underestimation of the dose. On the other hand, Instillagel® and Space OAR™ “shrinks” objects in an ultrasound image for 0.65 mm and 0.40 mm, respectively. Conclusions The use of EA 4015 Silicone Standoff kit for image acquisition, leads to erroneous contouring of PTV and OARs and reconstruction and placement of catheters, which results to incorrect dose calculation during prostate brachytherapy. Moreover, the reliability of QA procedures lies mostly in the right temperature of the water used for accurate simulation of real conditions of transrectal ultrasound imaging. PMID:23346130

Circulating Tumor Cells from Prostate Cancer Patients Interact with E-Selectin under Physiologic Blood Flow

PubMed Central

Gakhar, Gunjan; Navarro, Vicente N.; Jurish, Madelyn; Lee, Guang Yu.; Tagawa, Scott T.; Akhtar, Naveed H.; Seandel, Marco; Geng, Yue; Liu, He; Bander, Neil H.; Giannakakou, Paraskevi; Christos, Paul J.; King, Michael R.; Nanus, David M.

2013-01-01

Hematogenous metastasis accounts for the majority of cancer-related deaths, yet the mechanism remains unclear. Circulating tumor cells (CTCs) in blood may employ different pathways to cross blood endothelial barrier and establish a metastatic niche. Several studies provide evidence that prostate cancer (PCa) cell tethering and rolling on microvascular endothelium via E-selectin/E-selectin ligand interactions under shear flow theoretically promote extravasation and contribute to the development of metastases. However, it is unknown if CTCs from PCa patients interact with E-selectin expressed on endothelium, initiating a route for tumor metastases. Here we report that CTCs derived from PCa patients showed interactions with E-selectin and E-selectin expressing endothelial cells. To examine E-selectin-mediated interactions of PCa cell lines and CTCs derived from metastatic PCa patients, we used fluorescently-labeled anti-prostate specific membrane antigen (PSMA) monoclonal antibody J591-488 which is internalized following cell-surface binding. We employed a microscale flow device consisting of E-selectin-coated microtubes and human umbilical vein endothelial cells (HUVECs) on parallel-plate flow chamber simulating vascular endothelium. We observed that J591-488 did not significantly alter the rolling behavior in PCa cells at shear stresses below 3 dyn/cm2. CTCs obtained from 31 PCa patient samples showed that CTCs tether and stably interact with E-selectin and E-selectin expressing HUVECs at physiological shear stress. Interestingly, samples collected during disease progression demonstrated significantly more CTC/E-selectin interactions than samples during times of therapeutic response (p=0.016). Analysis of the expression of sialyl Lewis X (sLex) in patient samples showed that a small subset comprising 1.9-18.8% of CTCs possess high sLex expression. Furthermore, E-selectin-mediated interactions between prostate CTCs and HUVECs were diminished in the presence of anti-E-selectin neutralizing antibody. CTC-Endothelial interactions provide a novel insight into potential adhesive mechanisms of prostate CTCs as a means to initiate metastasis. PMID:24386459