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1.  Multi-parametric MRI of the Prostate Aids to Detect Lesion Progression: Case Report 
Multi-parametric MRI (MP-MRI) provides an accurate anatomical assessment of the tumor and its local staging. Herein we report a case of intermediate risk prostatic adenocarcinoma, initially followed on active surveillance, which upgraded from Gleason 7 (3+4) to Gleason 8 (4+4) on transrectal ultrasound/MRI (TRUS/MRI) fusion biopsy after progression of MR spectroscopic findings and review the role of MP-MRI in the follow-up of prostate cancer patients undergoing active surveillance.
doi:10.1097/RCT.0000000000000069
PMCID: PMC4101022  PMID: 24733004
prostate carcinoma; MRI; active surveillance; MR spectroscopy
2.  Comparison of Endorectal coil and Non-endorectal coil T2W and DW MRI at 3T for Localizing Prostate Cancer: Correlation with Whole-mount Histopathology 
Purpose
To compare utility of T2W and DW MRI obtained with and without an endorectal coil at 3T for localizing prostate cancer.
Materials and Methods
This IRB approved study included twenty patients (median PSA 8.4ng/mL). Patients underwent consecutive prostate MRIs at 3T, first with a surface coil alone, then with combination of surface, endorectal coils (dual coil) followed by robotic assisted radical prostatectomy. Lesions were mapped at time of acquisition on dual-coil T2W, DWI-MRI. To avoid bias, six months later non-endorectal coil T2W, DWI-MRI were mapped. Both MRI evaluations were performed by two readers blinded to pathology with differences resolved by consensus. A lesion-based correlation with whole mount histopathology was performed.
Results
At histopathology 51 cancer foci were present ranging in size from 2 to 60mm. The sensitivity of the endorectal dual-coil, non-endorectal coil MRIs were 0.76, 0.45, respectively. PPVs for endorectal dual-coil, non-endorectal coil MRI were 0.80, 0.64, respectively. Mean size of detected lesions with non-endorectal coil MRI were larger than those detected by dual-coil MRI (22mm vs. 17.4mm).
Conclusion
Dual-coil prostate MRI detected more cancer foci than non-endorectal coil MRI. While non-endorectal coil MRI is an attractive alternative, physicians performing prostate MRI should be aware of its limitations.
doi:10.1002/jmri.24317
PMCID: PMC4016166  PMID: 24243824
prostate cancer; surface coil; endorectal coil; MRI; 3 Tesla
3.  Prostate Biopsy for the Interventional Radiologist 
Prostate biopsies are usually performed by urologists in the office setting using transrectal ultrasound (TRUS) guidance. The current standard of care involves obtaining 10–14 cores from different anatomical sections. These biopsies are usually not directed into a specific lesion as most prostate cancers are not visible on TRUS. Color-Doppler, ultrasound contrast agents, elastography, MRI, and MRI/ultrasound fusion are proposed as imaging methods to guide prostate biopsies. Prostate MRI and fusion biopsy create opportunities for diagnostic and interventional radiologists to play an increasingly important role in the screening, evaluation, diagnosis, targeted biopsy, surveillance and focal therapy of the prostate cancer patient.
doi:10.1016/j.jvir.2013.12.568
PMCID: PMC4308315  PMID: 24581731
4.  Upgrading prostate cancer following proton beam therapy 
Urology Annals  2015;7(2):262-264.
Pre- and post-radiation therapy (RT) effects on prostate histology have not been rigorously studied, but there appears to be a correlation between escalating radiation dosage and increasing post-RT histologic changes. Despite this dose-response relationship, radiation-induced changes may be heterogenous among different patients and even within a single tumor. When assessing residual tumor it is important to understand biopsy evaluation in the post-RT setting. We present the case of a poorly differentiated prostate adenocarcinoma following proton beam RT in a 45-year-old man with pre-RT Gleason 4 + 3 = 7 disease diagnosed in the setting of an elevated serum prostate-specific antigen level.
doi:10.4103/0974-7796.152944
PMCID: PMC4374273  PMID: 25837674
Biopsy; proton beam; prostate adenocarcinoma; radiation-induced changes
5.  Focal Therapy: Patients, Interventions, and Outcomes—A Report from a Consensus Meeting 
European Urology  2015;67(4):771-777.
Background
Focal therapy as a treatment option for localized prostate cancer (PCa) is an increasingly popular and rapidly evolving field.
Objective
To gather expert opinion on patient selection, interventions, and meaningful outcome measures for focal therapy in clinical practice and trial design.
Design, setting, and participants
Fifteen experts in focal therapy followed a modified two-stage RAND/University of California, Los Angeles (UCLA) Appropriateness Methodology process. All participants independently scored 246 statements prior to rescoring at a face-to-face meeting. The meeting occurred in June 2013 at the Royal Society of Medicine, London, supported by the Wellcome Trust and the UK Department of Health.
Outcome measurements and statistical analysis
Agreement, disagreement, or uncertainty were calculated as the median panel score. Consensus was derived from the interpercentile range adjusted for symmetry level.
Results and limitations
Of 246 statements, 154 (63%) reached consensus. Items of agreement included the following: patients with intermediate risk and patients with unifocal and multifocal PCa are eligible for focal treatment; magnetic resonance imaging–targeted or template-mapping biopsy should be used to plan treatment; planned treatment margins should be 5 mm from the known tumor; prostate volume or age should not be a primary determinant of eligibility; foci of indolent cancer can be left untreated when treating the dominant index lesion; histologic outcomes should be defined by targeted biopsy at 1 yr; residual disease in the treated area of ≤3 mm of Gleason 3 + 3 did not need further treatment; and focal retreatment rates of ≤20% should be considered clinically acceptable but subsequent whole-gland therapy deemed a failure of focal therapy. All statements are expert opinion and therefore constitute level 5 evidence and may not reflect wider clinical consensus.
Conclusions
The landscape of PCa treatment is rapidly evolving with new treatment technologies. This consensus meeting provides guidance to clinicians on current expert thinking in the field of focal therapy.
Patient summary
In this report we present expert opinion on patient selection, interventions, and meaningful outcomes for clinicians working in focal therapy for prostate cancer.
Take Home Message
Focal therapy as an active treatment for prostate cancer is rapidly evolving. Expert opinion gathered in this report using robust consensus methodology captures current thinking and can help direct future research and clinical care.
doi:10.1016/j.eururo.2014.09.018
PMCID: PMC4410301  PMID: 25281389
Prostatic neoplasms; Consensus development conference; Organ-sparing treatments
6.  Is Visual Registration Equivalent to Semiautomated Registration in Prostate Biopsy? 
BioMed Research International  2015;2015:394742.
In magnetic resonance iimaging- (MRI-) ultrasound (US) guided biopsy, suspicious lesions are identified on MRI, registered on US, and targeted during biopsy. The registration can be performed either by a human operator (visual registration) or by fusion software. Previous studies showed that software registration is fairly accurate in locating suspicious lesions and helps to improve the cancer detection rate. Here, the performance of visual registration was examined for ability to locate suspicious lesions defined on MRI. This study consists of 45 patients. Two operators with differing levels of experience (<1 and 18 years) performed visual registration. The overall spatial difference by the two operators in 72 measurements was 10.6 ± 6.0 mm. Each operator showed a spatial difference of 9.4 ± 5.1 mm (experienced; 39 lesions) and 12.1 ± 6.6 mm (inexperienced; 33 lesions), respectively. In a head-to-head comparison of the same 16 lesions from 12 patients, the spatial differences were 9.7 mm ± 4.9 mm (experienced) and 13.4 mm ± 7.4 mm (inexperienced). There were significant differences between the two operators (unpaired, P value = 0.042; paired, P value = 0.044). The substantial differences by the two operators suggest that visual registration could improperly and inaccurately target many tumors, thereby potentially leading to missed diagnosis or false characterization on pathology.
doi:10.1155/2015/394742
PMCID: PMC4363498  PMID: 25821799
7.  Changes Observed in Multiparametric Prostate MRI Characteristics Correlate with Histopathological Development of Chronic Granulomatous Prostatitis Following Intravesical BCG Therapy 
Administration of Bacillus Calmette-Guerin (BCG) has been shown to cause granulomatous prostatitis, a rare inflammatory process that can be mistaken for prostate cancer (PCa). We present a case of a 78-year-old male on active surveillance (AS) for PCa with a subsequent diagnosis of high-grade urothelial carcinoma. Following intravesical BCG therapy, he developed chronic granulomatous prostatitis (CGP). We present serial MRI and biopsy data demonstrating the time interval between BCG administration and the manifestation of CGP.
doi:10.1097/RCT.0b013e3182aac58a
PMCID: PMC3995030  PMID: 24637671
Granulomatous prostatitis; intravesical BCG; prostate neoplasms; magnetic resonance imaging; ultrasound
8.  The role of magnetic resonance imaging (MRI) in focal therapy for prostate cancer: recommendations from a consensus panel 
BJU international  2013;113(2):218-227.
Objective
To establish a consensus on the utility of multiparametric magnetic resonance imaging (mpMRI) to identify patients for focal therapy.
Methods
Urological surgeons, radiologists, and basic researchers, from Europe and North America participated in a consensus meeting about the use of mpMRI in focal therapy of prostate cancer.The consensus process was face-to-face and specific clinical issues were raised and discussed with agreement sought when possible. All participants are listed among the authors.Topics specifically did not include staging of prostate cancer, but rather identifying the optimal requirements for performing MRI, and the current status of optimally performed mpMRI to (i) determine focality of prostate cancer (e.g. localising small target lesions of ≥0.5 mL), (ii) to monitor and assess the outcome of focal ablation therapies, and (iii) to identify the diagnostic advantages of new MRI methods.In addition, the need for transperineal template saturation biopsies in selecting patients for focal therapy was discussed, if a high quality mpMRI is available. In other words, can mpMRI replace the role of transperineal saturation biopsies in patient selection for focal therapy?
Results
Consensus was reached on most key aspects of the meeting; however, on definition of the optimal requirements for mpMRI, there was one dissenting voice.mpMRI is the optimum approach to achieve the objectives needed for focal therapy, if made on a high quality machine (3T with/without endorectal coil or 1.5T with endorectal coil) and judged by an experienced radiologist.Structured and standardised reporting of prostate MRI is paramount.State of the art mpMRI is capable of localising small tumours for focal therapy.State of the art mpMRI is the technique of choice for follow-up of focal ablation.
Conclusions
The present evidence for MRI in focal therapy is limited.mpMRI is not accurate enough to consistently grade tumour aggressiveness.Template-guided saturation biopsies are no longer necessary when a high quality state of the art mpMRI is available; however, suspicious lesions should always be confirmed by (targeted) biopsy.
doi:10.1111/bju.12243
PMCID: PMC4131409  PMID: 24215670
prostate cancer; focal therapy; consensus; multiparametric magnetic resonance imaging; prostate biopsies
9.  Imaging and pathology findings after an initial negative MRI-US fusion-guided and 12-core extended sextant prostate biopsy session 
PURPOSE
A magnetic resonance imaging-ultrasonography (MRI-US) fusion-guided prostate biopsy increases detection rates compared to an extended sextant biopsy. The imaging characteristics and pathology outcomes of subsequent biopsies in patients with initially negative MRI-US fusion biopsies are described in this study.
MATERIALS AND METHODS
We reviewed 855 biopsy sessions of 751 patients (June 2007 to March 2013). The fusion biopsy consisted of two cores per lesion identified on multiparametric MRI (mpMRI) and a 12-core extended sextant transrectal US (TRUS) biopsy. Inclusion criteria were at least two fusion biopsy sessions, with a negative first biopsy and mpMRI before each.
RESULTS
The detection rate on the initial fusion biopsy was 55.3%; 336 patients had negative findings. Forty-one patients had follow-up fusion biopsies, but only 34 of these were preceded by a repeat mpMRI. The median interval between biopsies was 15 months. Fourteen patients (41%) were positive for cancer on the repeat MRI-US fusion biopsy. Age, prostate- specific antigen (PSA), prostate volume, PSA density, digital rectal exam findings, lesion diameter, and changes on imaging were comparable between patients with negative and positive rebiopsies. Of the patients with positive rebiopsies, 79% had a positive TRUS biopsy before referral (P = 0.004). Ten patients had Gleason 3+3 disease, three had 3+4 disease, and one had 4+4 disease.
CONCLUSION
In patients with a negative MRI-US fusion prostate biopsy and indications for repeat biopsy, the detection rate of the follow-up sessions was lower than the initial detection rate. Of the prostate cancers subsequently found, 93% were low grade (≤3+4). In this low risk group of patients, increasing the follow-up time interval should be considered in the appropriate clinical setting.
doi:10.5152/dir.2014.13345
PMCID: PMC4289157  PMID: 24509182
10.  Perioperative, Functional, and Oncologic Outcomes of Partial Adrenalectomy for Multiple Ipsilateral Pheochromocytomas 
Journal of Endourology  2014;28(1):112-116.
Abstract
Objective: Managing patients with multiple adrenal masses is technically challenging. We present our experience with minimally invasive partial adrenalectomy (PA) performed for synchronous multiple ipsilateral pheochromocytomas in a single setting.
Materials and Methods: We reviewed records of patients undergoing PA for pheochromocytoma at the National Cancer Institute between 1994 and 2010. Patients were included if multiple tumors were excised from the ipsilateral adrenal gland in the same operative setting. Perioperative, functional, and oncologic outcomes of PA for multiple pheochromocytomas are shown.
Results: Of 121 partial adrenalectomies performed, 10 procedures performed in eight patients for synchronous multiple ipsilateral pheochromocytomas were identified. All eight patients were symptomatic at presentation. The mean patient age was 30.6 years, median follow up was 12 months. The average surgical time was 228 minutes, average blood loss of 125 mL, and average number of tumors removed was 2.6 per adrenal. In total, 26 tumors were removed, 24 were pathologically confirmed pheochromocytomas, while two were adrenal cortical hyperplasia. After surgery, all patients had resolution of their symptoms, one patient required steroid replacement postoperatively. On postoperative imaging, one patient had evidence of ipsilateral adrenal nodule at the prior resection site 2 months postoperatively, which was consistent with incomplete resection.
Conclusions: Minimally invasive surgical resection of synchronous multiple pheochromocytomas is feasible with acceptable perioperative, functional, and short-term oncologic outcomes.
doi:10.1089/end.2013.0298
PMCID: PMC3880898  PMID: 23998199
11.  Image-guided focal therapy for prostate cancer 
The adoption of routine prostate specific antigen screening has led to the discovery of many small and low-grade prostate cancers which have a low probability of causing mortality. These cancers, however, are often treated with radical therapies resulting in long-term side effects. There has been increasing interest in minimally invasive focal therapies to treat these tumors. While imaging modalities have improved rapidly over the past decade, similar advances in image-guided therapy are now starting to emerge—potentially achieving equivalent oncologic efficacy while avoiding the side effects of conventional radical surgery. The purpose of this article is to review the existing literature regarding the basis of various focal therapy techniques such as cryotherapy, microwave, laser, and high intensity focused ultrasound, and to discuss the results of recent clinical trials that demonstrate early outcomes in patients with prostate cancer.
doi:10.5152/dir.2014.14134
PMCID: PMC4463293  PMID: 25205025
12.  Accuracy analysis in MRI-guided robotic prostate biopsy 
Purpose
To assess retrospectively the clinical accuracy of an magnetic resonance imaging-guided robotic prostate biopsy system that has been used in the US National Cancer Institute for over 6 years.
Methods
Series of 2D transverse volumetric MR image slices of the prostate both pre (high-resolution T2-weighted)-and post (low-resolution)-needle insertions were used to evaluate biopsy accuracy. A three-stage registration algorithm consisting of an initial two-step rigid registration followed by a B-spline deformable alignment was developed to capture prostate motion during biopsy. The target displacement (distance between planned and actual biopsy target), needle placement error (distance from planned biopsy target to needle trajectory), and biopsy error (distance from actual biopsy target to needle trajectory) were calculated as accuracy assessment.
Results
A total of 90 biopsies from 24 patients were studied. The registrations were validated by checking prostate contour alignment using image overlay, and the results were accurate to within 2 mm. The mean target displacement, needle placement error, and clinical biopsy error were 5.2, 2.5, and 4.3 mm, respectively.
Conclusion
The biopsy error reported suggests that quantitative imaging techniques for prostate registration and motion compensation may improve prostate biopsy targeting accuracy.
doi:10.1007/s11548-013-0831-9
PMCID: PMC4139961  PMID: 23532560
Prostate biopsy; Accuracy validation; MRI-guidance; Image registration
13.  Preliminary evaluation of urinary soluble Met as a Biomarker for urothelial carcinoma of the bladder 
Background
Among genitourinary malignancies, bladder cancer (BCa) ranks second in both prevalence and cause of death. Biomarkers of BCa for diagnosis, prognosis and disease surveillance could potentially help prevent progression, improve survival rates and reduce health care costs. Among several oncogenic signaling pathways implicated in BCa progression is that of hepatocyte growth factor (HGF) and its cell surface receptor, Met, now targeted by 25 experimental anti-cancer agents in human clinical trials. The involvement of this pathway in several cancers is likely to preclude the use of urinary soluble Met (sMet), which has been correlated with malignancy, for initial BCa screening. However, its potential utility as an aid to disease surveillance and to identify patients likely to benefit from HGF/Met-targeted therapies provide the rationale for this preliminary retrospective study comparing sMet levels between benign conditions and primary BCa, and in BCa cases, between different disease stages.
Methods
Normally voided urine samples were collected from patients with BCa (Total: 183; pTa: 55, pTis: 62, pT1: 24, pT2: 42) and without BCa (Total: 83) on tissue-procurement protocols at three institutions and sMet was measured and normalized to urinary creatinine. Normalized sMet values grouped by pathologic stage were compared using non-parametric tests for correlation and significant difference. ROC analyses were used to derive classification models for patients with or without BCa and patients with or without muscle-invasive BCa (MIBCa or NMIBCa).
Results
Urinary sMet levels accurately distinguished patients with BCa from those without (p < 0.0001, area under the curve (AUC): 0.7008) with limited sensitivity (61%) and moderate specificity (76%), and patients with MIBCa (n = 42) from those with NMIBCa (n = 141; p < 0.0001, AUC: 0.8002) with moderate sensitivity and specificity (76% and 77%, respectively) and low false negative rate (8%).
Conclusions
Urinary sMet levels distinguish patients with BCa from those without, and patients with or without MIBCa, suggesting the potential utility of urinary sMet as a BCa biomarker for surveillance following initial treatment. Further studies are warranted to determine its potential value for prognosis in advanced disease, predicting treatment response, or identifying patients likely to benefit from Met-targeted therapies.
doi:10.1186/1479-5876-12-199
PMCID: PMC4283116  PMID: 25335552
Urothelial carcinoma; Bladder cancer; Biomarker; HGF receptor; Met; Urine
14.  Whole Prostate Volume and Shape Changes with the Use of an Inflatable and Flexible Endorectal Coil 
Purpose. To determine to what extent an inflatable endorectal coil (ERC) affects whole prostate (WP) volume and shape during prostate MRI. Materials and Methods. 79 consecutive patients underwent T2W MRI at 3T first with a 6-channel surface coil and then with the combination of a 16-channel surface coil and ERC in the same imaging session. WP volume was assessed by manually contouring the prostate in each T2W axial slice. PSA density was also calculated. The maximum anterior-posterior (AP), left-right (LR), and craniocaudal (CC) prostate dimensions were measured. Changes in WP prostate volume, PSA density, and prostate dimensions were then evaluated. Results. In 79 patients, use of an ERC yielded no significant change in whole prostate volume (0.6 ± 5.7%, P = 0.270) and PSA density (−0.2 ± 5.6%, P = 0.768). However, use of an ERC significantly decreased the AP dimension of the prostate by −8.6 ± 7.8% (P < 0.001), increased LR dimension by 4.5 ± 5.8% (P < 0.001), and increased the CC dimension by 8.8 ± 6.9% (P < 0.001). Conclusion. Use of an ERC in prostate MRI results in the shape deformation of the prostate gland with no significant change in the volume of the prostate measured on T2W MRI. Therefore, WP volumes calculated on ERC MRI can be reliably used in clinical workflow.
doi:10.1155/2014/903747
PMCID: PMC4211158  PMID: 25374680
15.  Multiparametric MRI in the PSA Screening Era 
BioMed Research International  2014;2014:465816.
Prostate cancer remains significant public health concern amid growing controversies regarding prostate specific antigen (PSA) based screening. The utility of PSA has been brought into question, and alternative measures are investigated to remedy the overdetection of indolent disease and safeguard patients from the potential harms resulting from an elevated PSA. Multiparametric MRI of the prostate has shown promise in identifying patients at risk for clinically significant disease but its role within the current diagnostic and treatment paradigm remains in question. The current review focuses on recent applications of MRI in this pathway.
doi:10.1155/2014/465816
PMCID: PMC4163437  PMID: 25250323
16.  Editorial Comments 
The Journal of urology  2012;189(1):92.
doi:10.1016/j.juro.2012.08.261
PMCID: PMC4136648  PMID: 23158414
17.  Magnetic resonance imaging (MRI)-guided transurethral ultrasound therapy of the prostate: a preclinical study with radiological and pathological correlation using customised MRI-based moulds 
BJU international  2013;112(4):10.1111/bju.12126.
Objective
To characterise the feasibility and safety of a novel transurethral ultrasound (US)-therapy device combined with real-time multi-plane magnetic resonance imaging (MRI)-based temperature monitoring and temperature feedback control, to enable spatiotemporally precise regional ablation of simulated prostate gland lesions in a preclinical canine model.
To correlate ablation volumes measured with intra-procedural cumulative thermal damage estimates, post-procedural MRI, and histopathology.
Materials and methods
Three dogs were treated with three targeted ablations each, using a prototype MRI-guided transurethral US-therapy system (Philips Healthcare, Vantaa, Finland).
MRI provided images for treatment planning, guidance, real-time multi-planar thermometry, as well as post-treatment evaluation of efficacy.
After treatment, specimens underwent histopathological analysis to determine the extent of necrosis and cell viability.
Statistical analyses (Pearson’s correlation, Student’s t-test) were used to evaluate the correlation between ablation volumes measured with intra-procedural cumulative thermal damage estimates, post-procedural MRI, and histopathology.
Results
MRI combined with a transurethral US-therapy device enabled multi-planar temperature monitoring at the target as well as in surrounding tissues, allowing for safe, targeted, and controlled ablations of prescribed lesions.
Ablated volumes measured by cumulative thermal dose positively correlated with volumes determined by histopathological analysis (r2 0.83, P < 0.001).
Post-procedural contrast-enhanced and diffusion-weighted MRI showed a positive correlation with non-viable areas on histopathological analysis (r2 0.89, P < 0.001, and r20.91, P = 0.003, respectively).
Additionally, there was a positive correlation between ablated volumes according to cumulative thermal dose and volumes identified on post-procedural contrast-enhanced MRI (r2 0.77, P < 0.01).
There was no difference in mean ablation volumes assessed with the various analysis methods (P > 0.05, Student’s t-test).
Conclusions
MRI-guided transurethral US therapy enabled safe and targeted ablations of prescribed lesions in a preclinical canine prostate model.
Ablation volumes were reliably predicted by intra- and post-procedural imaging.
Clinical studies are needed to confirm the feasibility, safety, oncological control, and functional outcomes of this therapy in patients in whom focal therapy is indicated.
doi:10.1111/bju.12126
PMCID: PMC3816743  PMID: 23746198
thermal ablation; therapeutic ultrasound; thermotherapy; minimally invasive therapy; magnetic resonance imaging; image-guided therapy
18.  Multiparametric MRI in Biopsy Guidance for Prostate Cancer: Fusion-Guided 
BioMed Research International  2014;2014:439171.
Prostate cancer (PCa) is the most common solid-organ malignancy among American men and the second most deadly. Current guidelines recommend a 12-core systematic biopsy following the finding of an elevated serum prostate-specific antigen (PSA). However, this strategy fails to detect an unacceptably high percentage of clinically significant cancers, leading researchers to develop new, innovative methods to improve the effectiveness of prostate biopsies. Multiparametric-MRI (MP-MRI) has emerged as a promising instrument in identifying suspicious regions within the prostate that require special attention on subsequent biopsy. Fusion platforms, which incorporate the MP-MRI into the biopsy itself and provide active targets within real-time imaging, have shown encouraging results in improving the detection rate of significant cancer. Broader applications of this technology, including MRI-guided focal therapy for prostate cancer, are in early phase trials.
doi:10.1155/2014/439171
PMCID: PMC4122009  PMID: 25126559
19.  Natural history of small index lesions suspicious for prostate cancer on multiparametric MRI: recommendations for interval imaging follow-up 
PURPOSE
We aimed to determine the natural history of small index lesions identified on multiparametric-magnetic resonance imaging (MP-MRI) of the prostate by evaluating lesion-specific pathology and growth on serial MP-MRI.
MATERIALS AND METHODS
We performed a retrospective review of 153 patients who underwent a minimum of two MP-MRI sessions, on an institutional review board-approved protocol. Index lesion is defined as the lesion(s) with the highest cancer suspicion score based on initial MP-MRI of a patient, irrespective of size. Two study cohorts were identified: (1) patients with no index lesion or index lesion(s) ≤7 mm and (2) a subset with no index lesion or index lesion(s) ≤5 mm. Pathological analysis of the index lesions was performed following magnetic resonance/ultrasound fusion-guided biopsy. Growth rate of the lesions was calculated based on MP-MRI follow-up.
RESULTS
Patients with small index lesions measuring ≤7 mm (n=42) or a subset with lesions ≤5 mm (n=20) demonstrated either benign findings (86.2% and 87.5%, respectively) or low grade Gleason 6 prostate cancer (13.8% and 12.5%, respectively) on lesion-specific targeted biopsies. These lesions demonstrated no significant change in size (P = 0.93 and P = 0.36) over a mean imaging period of 2.31±1.56 years and 2.40±1.77 years for ≤7 mm and ≤5 mm index lesion thresholds, respectively. These findings held true on subset analyses of patients who had a minimum of two-year interval follow-up with MP-MRI.
CONCLUSION
Small index lesions of the prostate are pathologically benign lesions or occasionally low-grade cancers. Slow growth rate of these small index lesions on serial MP-MRI suggests a surveillance interval of at least two years without significant change.
doi:10.5152/dir.2014.13319
PMCID: PMC4463272  PMID: 24808435
20.  Localized Prostate Cancer Detection with 18F FACBC PET/CT: Comparison with MR Imaging and Histopathologic Analysis 
Radiology  2013;270(3):849-856.
Although 18F FACBC PET/CT is not likely to have utility as an independent modality in the evaluation of localized prostate cancer, its use with conventional or multiparametric MR imaging can lead to more accurate localization of prostate cancer lesions.
Purpose
To characterize uptake of 1-amino-3-fluorine 18-fluorocyclobutane-1-carboxylic acid (18F FACBC) in patients with localized prostate cancer, benign prostatic hyperplasia (BPH), and normal prostate tissue and to evaluate its potential utility in delineation of intraprostatic cancers in histopathologically confirmed localized prostate cancer in comparison with magnetic resonance (MR) imaging.
Materials and Methods
Institutional review board approval and written informed consent were obtained for this HIPAA-compliant prospective study. Twenty-one men underwent dynamic and static abdominopelvic 18F FACBC combined positron emission tomography (PET) and computed tomography (CT) and multiparametric (MP) 3-T endorectal MR imaging before robotic-assisted prostatectomy. PET/CT and MR images were coregistered by using pelvic bones as fiducial markers; this was followed by manual adjustments. Whole-mount histopathologic specimens were sliced with an MR-based patient-specific mold. 18F FACBC PET standardized uptake values (SUVs) were compared with those at MR imaging and histopathologic analysis for lesion- and sector-based (20 sectors per patient) analysis. Positive and negative predictive values for each modality were estimated by using generalized estimating equations with logit link function and working independence correlation structure.
Results
18F FACBC tumor uptake was rapid but reversible. It peaked 3.6 minutes after injection and reached a relative plateau at 15–20 minutes (SUVmax[15–20min]). Mean prostate tumor SUVmax(15–20min) was significantly higher than that of the normal prostate (4.5 ± 0.5 vs 2.7 ± 0.5) (P < .001); however, it was not significantly different from that of BPH (4.3 ± 0.6) (P = .27). Sector-based comparison with histopathologic analysis, including all tumors, revealed sensitivity and specificity of 67% and 66%, respectively, for 18F FACBC PET/CT and 73% and 79%, respectively, for T2-weighted MR imaging. 18F FACBC PET/CT and MP MR imaging were used to localize dominant tumors (sensitivity of 90% for both). Combined 18F FACBC and MR imaging yielded positive predictive value of 82% for tumor localization, which was higher than that with either modality alone (P < .001).
Conclusion
18F FACBC PET/CT shows higher uptake in intraprostatic tumor foci than in normal prostate tissue; however, 18F FACBC uptake in tumors is similar to that in BPH nodules. Thus, it is not specific for prostate cancer. Nevertheless, combined 18F FACBC PET/CT and T2-weighted MR imaging enable more accurate localization of prostate cancer lesions than either modality alone.
© RSNA, 2013
Online supplemental material is available for this article.
doi:10.1148/radiol.13130240
PMCID: PMC4263644  PMID: 24475804
21.  Imaging and pathology findings after an initial negative MRI-US fusion-guided and 12-core extended sextant prostate biopsy session 
PURPOSE
A magnetic resonance imaging-ultrasonography (MRI-US) fusion-guided prostate biopsy increases detection rates compared to an extended sextant biopsy. The imaging characteristics and pathology outcomes of subsequent biopsies in patients with initially negative MRI-US fusion biopsies are described in this study.
MATERIALS AND METHODS
We reviewed 855 biopsy sessions of 751 patients (June 2007 to March 2013). The fusion biopsy consisted of two cores per lesion identified on multiparametric MRI (mpMRI) and a 12-core extended sextant transrectal US (TRUS) biopsy. Inclusion criteria were at least two fusion biopsy sessions, with a negative first biopsy and mpMRI before each.
RESULTS
The detection rate on the initial fusion biopsy was 55.3%; 336 patients had negative findings. Forty-one patients had follow-up fusion biopsies, but only 34 of these were preceded by a repeat mpMRI. The median interval between biopsies was 15 months. Fourteen patients (41%) were positive for cancer on the repeat MRI-US fusion biopsy. Age, prostate-specific antigen (PSA), prostate volume, PSA density, digital rectal exam findings, lesion diameter, and changes on imaging were comparable between patients with negative and positive rebiopsies. Of the patients with positive rebiopsies, 79% had a positive TRUS biopsy before referral (P = 0.004). Ten patients had Gleason 3+3 disease, three had 3+4 disease, and one had 4+4 disease.
CONCLUSION
In patients with a negative MRI-US fusion prostate biopsy and indications for repeat biopsy, the detection rate of the follow-up sessions was lower than the initial detection rate. Of the prostate cancers subsequently found, 93% were low grade (≤3+4). In this low risk group of patients, increasing the follow-up time interval should be considered in the appropriate clinical setting.
doi:10.5152/dir.2014.13345
PMCID: PMC4289157  PMID: 24509182
22.  Gaussian Process Inference for Estimating Pharmacokinetic Parameters of Dynamic Contrast-Enhanced MR Images 
In this paper, we propose a new pharmacokinetic model for parameter estimation of dynamic contrast-enhanced (DCE) MRI by using Gaussian process inference. Our model is based on the Tofts dual-compartment model for the description of tracer kinetics and the observed time series from DCE-MRI is treated as a Gaussian stochastic process. The parameter estimation is done through a maximum likelihood approach and we propose a variant of the coordinate descent method to solve this likelihood maximization problem. The new model was shown to outperform a baseline method on simulated data. Parametric maps generated on prostate DCE data with the new model also provided better enhancement of tumors, lower intensity on false positives, and better boundary delineation when compared with the baseline method. New statistical parameter maps from the process model were also found to be informative, particularly when paired with the PK parameter maps.
PMCID: PMC3936338  PMID: 23286178
DCE-MRI; Gaussian Stochastic Process; Pharmacokinetic Model; Bayesian Inference; Coordinate Descent Optimization
24.  Feasibility and Outcomes of Laparoscopic Renal Intervention After Prior Open Ipsilateral Retroperitoneal Surgery 
Journal of Endourology  2013;27(2):196-201.
Abstract
Background and Purpose
Treating patients with renal-cell carcinoma (RCC) after previous retroperitoneal surgery (renal or adrenal) is technically challenging. We present our initial experience with laparoscopic renal interventions (LRI) after previousopen retroperitoneal surgery in patients needing ipsilateral renal intervention. We report on feasibility, functional and oncologic outcomes of LRI after previous open retroperitoneal surgery.
Patients and Methods
We reviewed records of patients undergoing attempted laparoscopic or robot-assisted renal intervention after at least one previous open ipsilateral retroperitoneal surgery. We identified 34 patients who underwent 39 staged attempted LRI after 48 previous open ipsilateral renal or adrenal surgeries. The LRI included 20 minimally invasive partial nephrectomies (MIPN), 11 laparoscopic radiofrequency ablations (LRFA), and 8 laparoscopic nephrectomies (LTN). Demographic, perioperative, renal functional, and oncologic outcome data were collected. Statistical analyses were performed to identify risks for conversion to open surgery.
Results
No attempted nephron-sparing procedure resulted in kidney loss. Overall conversion rate of the cohort was 28% and was highest in the MIPN group (40%). On univariate analysis, only multiple tumors that were treated significantly increased chances of open conversion (P<0.01). Subset analysis demonstrated similar rates of blood loss, operative times, and conversion rates in patients undergoing partial nephrectomy having previous open partial nephrectomy compared with previous open adrenal surgery only. There was no significant difference in preservation of renal function between MIPN and LRFA, with more than 85% of preoperative renal function preserved. Mean follow-up of 11.9 months (range 1–97.5 mos) metastasis-free survival and overall survival was 94.1% and 97%, respectively.
Conclusions
LRI after previous open ipsilateral retroperitoneal surgery is feasible. Repeated partial nephrectomy has the highest conversion risks among the laparoscopic renal interventions and appears to be independent of previous renal or adrenal procedure. Attempting repeated LRI for multiple tumors is a significant risk factor for open conversion. Renal functional and oncologic outcomes are encouraging at early follow-up.
doi:10.1089/end.2012.0483
PMCID: PMC3573724  PMID: 22963658
25.  Multiparametric Magnetic Resonance Imaging and Ultrasound Fusion Biopsy Detects Prostate Cancer in Patients with Prior Negative TRUS Biopsies 
The Journal of urology  2012;188(6):2152-2157.
Background
Patients with negative TRUS biopsies yet persistently rising PSA values are at risk for occult but significant prostate cancers. The ability of multiparametric MRI and ultrasound (MRI/US) fusion biopsy to detect these occult prostate lesions may make it an effective tool in this challenging scenario.
Methods
Men with one or more negative systematic prostate biopsies participated in this trial. Between March 2007 and November 2011 all men underwent prostate 3T endorectal coil MRI and MRI/US fusion biopsy. In addition, all patients underwent standard 12 core TRUS biopsy in addition to targeted MRI/US fusion biopsy of concerning lesions identified on MRI.
Results
Of the 195 men with previous negative biopsies, 73 (37%) were found to have cancer using the MRI/US fusion platform combined with 12 core TRUS biopsy. High grade cancer (Gleason sum 8+) was discovered in 21 men (11%). All 21 men with high grade disease (100%) were detected with MRI/US fusion targeted biopsy while standard TRUS biopsy missed 12 of these high grade cancers (55%). Upgrading occurred in 28 men (38.9%) as a result of MRI targeting versus standard TRUS biopsy. The diagnostic yield of MRI with guided biopsy was unrelated to the number of previous negative biopsies, and persisted despite increasing number of previous biopsy sessions. On multivariable analysis, only PSAD and MRI suspicion level remained significant predictors of cancer.
Conclusion
Multiparametric MRI in conjunction with a MRI/US fusion biopsy platform is a novel diagnostic tool for detecting prostate cancer and may be ideally suited for patients with negative TRUS biopsies in the face of a persistent clinical suspicion for cancer.
doi:10.1016/j.juro.2012.08.025
PMCID: PMC3895467  PMID: 23083875

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