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1.  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
2.  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
3.  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
4.  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
5.  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
6.  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
7.  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
8.  Editorial Comments 
The Journal of urology  2012;189(1):92.
doi:10.1016/j.juro.2012.08.261
PMCID: PMC4136648  PMID: 23158414
9.  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
10.  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
11.  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
13.  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
14.  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
15.  Robot-Assisted Laparoscopic Partial Nephrectomy for Tumors Greater than 4 cm and High Nephrometry Score: Feasibility, Renal Functional and Oncological Outcomes with Minimum 1 Year Follow-up 
Urologic oncology  2011;31(1):51-56.
Objectives
Minimally invasive robotic assistance is being increasingly utilized to treat larger complex renal masses. We report on the technical feasibility and renal functional and oncological outcomes with minimum 1 year follow up of robot-assisted laparoscopic partial nephrectomy (RALPN) for tumors greater than 4 cm.
Methods and Materials
The urologic oncology database was queried to identify patients treated with RALPN for tumors greater than 4 cm and a minimum follow up of 12 months. We identified 19 RALPN on 17 patients treated between June 2007 and July 2009. Two patients underwent staged bilateral RALPN. Demographic, operative, and pathologic data were collected. Renal function was assessed by serum creatinine levels, estimated glomerular filtration rate and nuclear renal scans assessed at baseline, 3 and 12 months post-operatively. All tumors were assigned R.E.N.A.L. nephrometry scores (www.nephrometry.com).
Results
The median nephrometry score for the largest tumor from each kidney was 9 (range 6–11) while the median size was 5 cm (range 4.1–15). Three of 19 cases (16%) required intraoperative conversion to open partial nephrectomy. No renal units were lost. There were no statistically significant differences between preoperative and postoperative creatinine and eGFR. A statistically significant decline of ipsilateral renal scan function (49% vs. 46.5%, p=0.006) was observed at three months and at twelve months postoperatively (49% vs. 45.5%, p=0.014). No patients had evidence of recurrence or metastatic disease at a median follow up of 22 months (range 12–36).
Conclusions
RALPN is feasible for renal tumors greater than 4 cm with moderate or high nephrometry scores. Although there was a modest decline in renal function of the operated unit, RALPN may afford the ability resect challenging tumors requiring complex renal reconstruction. The renal functional and oncological outcomes are promising at a median follow up of 22 months, but longer follow up is required.
doi:10.1016/j.urolonc.2010.10.008
PMCID: PMC3123423  PMID: 21292511
16.  Impact of Ischemia and Procurement Conditions on Gene Expression in Renal Cell Carcinoma 
Purpose
Previous studies have shown that ischemia alters gene expression in normal and malignant tissues. There are no studies that evaluated effects of ischemia in renal tumors. This study examines the impact of ischemia and tissue procurement conditions on RNA integrity and gene expression in renal cell carcinoma.
Experimental Design
Ten renal tumors were resected without renal hilar clamping from 10 patients with renal clear cell carcinoma. Immediately after tumor resection, a piece of tumor was snap frozen. Remaining tumor samples were stored at 4C, 22C and 37C and frozen at 5, 30, 60, 120, and 240 minutes. Histopathologic evaluation was performed on all tissue samples, and only those with greater than 80% tumor were selected for further analysis. RNA integrity was confirmed by electropherograms and quantitated using RIN index. Altered gene expression was assessed by paired, two-sample t-test between the zero time point and aliquots from various conditions obtained from the same tumor.
Results
One hundred and forty microarrays were performed. Some RNA degradation was observed 240 mins after resection at 37C. The expression of over 4,000 genes was significantly altered by ischemia times or storage conditions. The greatest gene expression changes were observed with longer ischemia time and warmer tissue procurement conditions.
Conclusion
RNA from kidney cancer remains intact for up to 4 hours post surgical resection regardless of storage conditions. Despite excellent RNA preservation, time after resection and procurement conditions significantly influence gene expression profiles. Meticulous attention to pre-acquisition variables is of paramount importance for accurate tumor profiling.
doi:10.1158/1078-0432.CCR-12-2606
PMCID: PMC3658320  PMID: 23136194
Ischemia; gene expression microarrays; tissue procurement; renal cell carcinoma
17.  Succinate Dehydrogenase Kidney Cancer (SDH-RCC): An Aggressive Example of the Warburg Effect in Cancer 
The Journal of urology  2012;188(6):10.1016/j.juro.2012.08.030.
Purpose
Recently, a new renal cell cancer (RCC) syndrome has been linked to germline mutation of multiple subunits (SDHB/C/D) of the Krebs cycle enzyme, succinate dehydrogenase. We report our experience with diagnosis, evaluation and treatment of this novel form of hereditary kidney cancer.
Materials and Methods
Patients with suspected hereditary kidney cancer were enrolled on an NCI-IRB approved protocol to study inherited forms of kidney cancer. Individuals from families with germline SDHB, SDHC and SDHD mutations and kidney cancer underwent comprehensive clinical and genetic evaluation.
Results
Fourteen patients from twelve SDHB mutation families were evaluated. Patients presented with RCC at an early age, 33 yrs (range 15–62 yrs), four developed metastatic kidney cancer and some families were found to have no manifestations other than kidney tumors. An additional family with six individuals found to have clear cell RCC that presented at a young average age, 47 yrs (range 40–53yrs), was identified with a germline SDHC mutation (R133X), two of which developed metastatic disease. A patient with a history of carotid body paragangliomas and a very aggressive form of kidney cancer was evaluated from a family with germline SDHD mutation.
Conclusions
SDH-RCC can be an aggressive type of kidney cancer, especially in younger individuals. Although detection and management of early tumors is most often associated with good outcome, based on our initial experience with these patients and our long term experience with HLRCC, we recommend careful surveillance of patients at risk for SDH-RCC and wide surgical excision of renal tumors.
doi:10.1016/j.juro.2012.08.030
PMCID: PMC3856891  PMID: 23083876
renal cell cancer (RCC); hereditary kidney cancer; Krebs cycle; Succinate dehydrogenase
18.  Partial Adrenalectomy Minimizes the Need for Long-Term Hormone Replacement in Pediatric Patients with Pheochromocytoma and von Hippel-Lindau Syndrome 
Journal of pediatric surgery  2012;47(11):10.1016/j.jpedsurg.2012.07.003.
Purpose
Children with von Hippel-Lindau syndrome are at an increased risk for developing bilateral pheochromocytomas. In an effort to illustrate the advantage of partial adrenalectomy (PA) over total adrenalectomy in children with VHL, we report the largest single series on PA for pediatric VHL patients, demonstrating a balance between tumor removal and preservation of adrenocortical function.
Methods
From 1994 to 2011, a prospectively maintained database was reviewed to evaluate 10 pediatric patients with hereditary pheochromocytoma for PA. Surgery was performed if there was clinical evidence of pheochromocytoma and normal adrenocortical tissue was evident on preoperative imaging and/or intraoperative ultrasonography. Perioperative data were collected and patients were followed for postoperative steroid use and tumor recurrence.
Results
Ten pediatric patients with a diagnosis of VHL underwent 18 successful partial adrenalectomies (4 open, 14 laparoscopic). The median tumor size removed was 2.6 centimeters (range 1.2–6.5). Over a median follow up of 7.2 years (range 2.6–15.8) additional tumors in the ipsilateral adrenal gland were found in two patients. One patient underwent completion adrenalectomy and one underwent a salvage PA with resection of the ipsilateral lesion. One patient required short term steroid replacement therapy. At last follow up, 7 patients had no radiographic or laboratory evidence of pheochromocytoma.
Conclusion
At our institution, partial adrenalectomy is the preferred form of management for pheochromocytoma in the (VHL) pediatric population. This surgical approach allows for removal of tumor while preserving adrenocortical function and minimizing the side effects of long term steroid replacement on puberty and quality of life.
doi:10.1016/j.jpedsurg.2012.07.003
PMCID: PMC3846393  PMID: 23164001
adrenalectomy; partial adrenalectomy; pediatric VHL; pheochromocytoma
19.  Low Suspicion Lesions on Multiparametric Magnetic Resonance Imaging Predict for the Absence of High Risk Prostate Cancer 
BJU international  2012;110(11 0 0):10.1111/j.1464-410X.2012.11646.x.
Background
Prostate cancer is currently diagnosed by random biopsies resulting in the discovery of multiple low risk cancers that often lead to overtreatment.
Multiparametric magnetic resonance imaging (mpMRI) may have the potential to identify patients at low risk for cancer, thus obviating the need for biopsy.
Methods
We reviewed 800 consecutive patients who underwent a 3 Tesla mpMRI of the prostate with endorectal coil from March 2007 to November 2011.
Two radiologists independently reviewed all suspicious lesions using T2-weighted, diffusion weighted, spectroscopic, and dynamic contrast enhanced MRI sequences.
Patients with only low suspicion lesions (maximum of two positive parameters on mpMRI) who subsequently underwent TRUS/MRI-fusion targeted biopsy were selected for analysis.
Results
One hundred and twenty-five patients with only low suspicion prostatic lesions on mpMRI were identified.
On TRUS/MRI-fusion biopsy, 77 of these patients (62%) had no cancer detected, 38 patients had Gleason 6 disease, and 10 patients had Gleason 7 (3+4) disease.
Thirty patients with cancer detected on biopsy qualified for active surveillance using 2011 NCCN guidelines.
No cases of high risk (≥ Gleason 4+3) cancer were identified on biopsy and of the fifteen patients that underwent radical prostatectomy at our institution, none were pathologically upgraded to high risk cancer.
Thus, for patients with only low suspicion lesions, 88% (107 patients) either had no cancer or clinically insignificant disease.
Conclusion
Our results demonstrate that low suspicion lesions on mpMRI are associated with either negative biopsies or low grade tumors suitable for active surveillance.
Such patients have a low risk of harboring high risk prostate cancers.
doi:10.1111/j.1464-410X.2012.11646.x
PMCID: PMC3808160  PMID: 23130821
20.  Economic burden of reoperative renal surgery on solitary kidney: Do the ends justify the means? A cost effectiveness analysis 
The Journal of urology  2012;188(5):10.1016/j.juro.2012.07.029.
Purpose
Despite the high morbidity of reoperative renal surgery (RRS) in patients with multifocal recurrent renal carcinoma, most patients are able to preserve adequate renal function to obviate the need for dialysis. The economic burden of RRS has not been evaluated. We aim to provide a cost-effectiveness analysis for patients requiring RRS on a solitary kidney.
Materials and Methods
We reviewed the charts of patients treated at the National Cancer Institute (NCI) requiring RRS from 1989 to 2010. Functional, oncological and surgical outcomes were evaluated, and the costs of RRS were calculated. We then compared the costs of a 33 patients cohort who underwent RRS on a solitary kidney and a hypothetical cohort of patients that would undergo uncomplicated nephrectomy, fistula placement and dialysis. All costs were calculated based on Medicare reimbursement rates derived from Current Procedural Terminology (CPT) codes. A cost-effectiveness analysis was applied.
Results
Despite a high complication rate (45%), 87% of patients maintained adequate renal function to avoid dialysis and 96% remained metastasis free at an average follow up of 3.12 years (range 0.3-16.4). When compared to hypothetical dialysis cohort, the financial benefit of RRS was reached at 0.68 years.
Conclusions
RRS is a viable alternative for patients with multifocal renal cell carcinoma requiring multiple surgical interventions, especially when left with a solitary kidney. Despite the high complication rate, most patients are able to preserve renal function and have excellent oncological outcomes. The financial benefit of RRS is reached at less than 1 year.
doi:10.1016/j.juro.2012.07.029
PMCID: PMC3817487  PMID: 22998899
Reoperative renal surgery; repeat partial nephrectomy; cost effectiveness; nephron sparing surgery
21.  Age related changes in prostate zonal volume as measured by high resolution prostate MRI: a cross sectional study in over 500 patients 
BJU international  2012;110(11):10.1111/j.1464-410X.2012.11469.x.
Objective
To utilize ability of MRI to investigate age related changes in zonal prostatic volumes.
Materials and Methods
This IRB approved, HIPAA compliant study consists 503 patients who underwent 3Tesla prostate MRI prior to any treatment for prostate cancer. Whole prostate (WP), central gland (CG) volumes were manually contoured on T2W MRI using a semi-automated segmentation tool. WP, CG, peripheral zone (PZ) volumes were measured for each patient. WP, CG, PZ volumes were correlated with age, serum PSA, IPSS, SHIM scores.
Results
Linear regression analysis demonstrated positive correlation between WP, CG volumes and patient age (p<0.0001); there was no correlation between age and PZ volume (p=0.173). There was positive correlation between WP, CG volumes and serum PSA (p<0.0001), as well as between PZ volume and serum PSA (p=0.0021). At logistic regression analysis, IPSS positively correlated with WP, CG volumes (p<0.0001). SHIM positively correlated with WP (p<0.0149), CG (p<0.0234) volumes. As expected, IPSS of patients with prostate volumes (WP, CG) in 1st decile for age were significantly lower than those in 10th decile.
Conclusion
Prostate MRI is able to document age related changes in zonal prostate volumes. Changes in WP, CG volumes correlated inversely with changes in lower urinary tract symptoms. These findings suggest a role for MRI in measuring accurate zonal volumes, have interesting implications for study of age related changes in prostate.
doi:10.1111/j.1464-410X.2012.11469.x
PMCID: PMC3816371  PMID: 22973825
BPH; MRI; prostate zonal volumes
22.  Outcomes of Patients with Surgically Treated Bilateral Renal Masses and a Minimum of 10 Years of Follow-Up 
The Journal of urology  2012;188(6):10.1016/j.juro.2012.08.038.
Background
While nephron-sparing surgery has been advocated for patients with bilateral renal masses, the long-term functional and oncological outcomes are lacking.
Objective
To determine the outcomes of patients with bilateral renal masses (BRM) and a minimum of 10 years of follow-up.
Design, Setting, and Participants
Patients with BRM evaluated at the National Cancer Institute who underwent their initial surgical intervention at least 10 years ago and had interventions on both renal units were included in our analysis. The data collected included demographics, hereditary diagnosis, number of renal interventions, renal function, and mortality status.
Intervention(s)
Bilateral renal surgery.
Outcome Measurements and Statistical Analysis
Overal and RCC specific survival was assessed. Comparisons of renal function and overall survival between groups containing both renal units and solitary kidneys were performed using the student T-test and Kaplan-Meier analysis.
Results and Limitations
128 patients met our inclusion criteria. The median follow-up of our cohort was 16 years (10-49), mean 17 years. The median number of surgical interventions was 3 (2-10). Eighty-seven patients (68%) required repeat interventions on their ipsilateral renal unit at last follow-up, with a median time between interventions of 6.2 years (0.7-21). Overall and RCC-specific survival of the cohort was 88% and 97%, respectively. Six patients (4.7%) ultimately underwent bilateral nephrectomies.
Although renal function was better preserved in patients with both kidneys (70 vs. 53 mL/min/1.73m2, P=0.0002) there was no difference in overall survival between those with bilateral or solitary kidneys (mean 21.5 vs. 20.8 years, respectively). Limitations of the study are in its retrospective design and inclusion of closely surveilled patients.
Conclusions
At a minimum of 10 years follow-up after initial surgery, nephron-sparing surgery allows for excellent oncologic and functional outcomes. Despite the need for repeat surgical interventions, employing NSS allows for avoidance of dialysis in over 95% of patients.
doi:10.1016/j.juro.2012.08.038
PMCID: PMC3810017  PMID: 23083858
Familial renal cancer (FRC); bilateral renal masses (BRM); nephron-sparing surgery (NSS); partial nephrectomy; outcomes
23.  Commentary on: “Focal cryosurgical ablation of the prostate: A single institute’s perspective” 
BMC Urology  2013;13:39.
The morbidity of whole gland treatment for prostate cancer is significant. Given the low risk of prostate cancer specific mortality for most men diagnosed with prostate cancer, alternative therapies such as sub-total or hemi-ablation of the prostate and focal ablation of prostate tumors are being investigated. The developing role of imaging for prostate tumors will dramatically change and likely improve the treatment morbidity for low risk prostate tumors. Commentary on: http://www.biomedcentral.com/1471-2490/13/2.
doi:10.1186/1471-2490-13-39
PMCID: PMC3750819  PMID: 23915359
Prostate cancer; Therapy; Focal; Cryoablation; Image guided surgery
24.  Renal Cell Carcinoma with Metastases to the Gallbladder: Four Cases from the National Cancer Institute (NCI) and Review of the Literature 
Urologic Oncology  2011;30(4):476-481.
Objective
We evaluate presentation and outcome of patients with metastatic RCC to the gallbladder from our institution and published literature.
Methods
Patients with a history of gallbladder metastasis from RCC were selected from our institution’s prospective database. A systematic PubMed search was performed to identify articles describing patients with metastatic RCC to the gallbladder. The final cohort included 33 patients: 4 from our institution and 29 from 28 previously published cases. Survival analysis was conducted using LogRank Kaplan-Meier analysis.
Results
Median patient age was 63 years and the majority of patients were male. Most patients were asymptomatic and diagnosed with gallbladder metastasis on imaging performed for surveillance or staging. The median time to gallbladder metastasis following nephrectomy was 4 years. Metastasis to the gallbladder occurred both synchronously (33%) and metachronously (67%). Of the patients with available histology, all had clear cell RCC (n=28). Of all patients, 13 (39%) only had metastasis to the gallbladder, while 20 (61%) had additional sites of metastasis. The most common sites of additional metastasis were contralateral kidney (30%), pancreas (21%), lung (18%), adrenal (18%), and lymph nodes (9%). All patients underwent cholecystectomy. At a median follow up time of 1.5 years after cholecystectomy, 54% of patients had no evidence of disease, 14% were alive with metastasis, 23% had died from metastatic RCC, and 9% died from causes unrelated to their cancer.
Conclusion
Gallbladder metastasis from RCC is a rare event that may occur synchronously or metachronously with most patients being asymptomatic. Clear cell carcinoma appears to be the primary pathology associated with gallbladder metastasis. High rates of bilateral RCC and pancreatic metastasis suggest novel associations in patients with RCC and gallbladder metastasis.
doi:10.1016/j.urolonc.2010.04.010
PMCID: PMC3145826  PMID: 21277810
renal cell carcinoma; bilateral RCC; metastatic kidney cancer; gallbladder metastases; pancreatic metastases
25.  Documenting the location of systematic transrectal ultrasound-guided prostate biopsies: correlation with multi-parametric MRI 
Cancer Imaging  2011;11(1):31-36.
Abstract
During transrectal ultrasound (TRUS)-guided prostate biopsies, the actual location of the biopsy site is rarely documented. Here, we demonstrate the capability of TRUS-magnetic resonance imaging (MRI) image fusion to document the biopsy site and correlate biopsy results with multi-parametric MRI findings. Fifty consecutive patients (median age 61 years) with a median prostate-specific antigen (PSA) level of 5.8 ng/ml underwent 12-core TRUS-guided biopsy of the prostate. Pre-procedural T2-weighted magnetic resonance images were fused to TRUS. A disposable needle guide with miniature tracking sensors was attached to the TRUS probe to enable fusion with MRI. Real-time TRUS images during biopsy and the corresponding tracking information were recorded. Each biopsy site was superimposed onto the MRI. Each biopsy site was classified as positive or negative for cancer based on the results of each MRI sequence. Sensitivity, specificity, and receiver operating curve (ROC) area under the curve (AUC) values were calculated for multi-parametric MRI. Gleason scores for each multi-parametric MRI pattern were also evaluated. Six hundred and 5 systemic biopsy cores were analyzed in 50 patients, of whom 20 patients had 56 positive cores. MRI identified 34 of 56 positive cores. Overall, sensitivity, specificity, and ROC area values for multi-parametric MRI were 0.607, 0.727, 0.667, respectively. TRUS-MRI fusion after biopsy can be used to document the location of each biopsy site, which can then be correlated with MRI findings. Based on correlation with tracked biopsies, T2-weighted MRI and apparent diffusion coefficient maps derived from diffusion-weighted MRI are the most sensitive sequences, whereas the addition of delayed contrast enhancement MRI and three-dimensional magnetic resonance spectroscopy demonstrated higher specificity consistent with results obtained using radical prostatectomy specimens.
doi:10.1102/1470-7330.2011.0007
PMCID: PMC3080122  PMID: 21450548
Prostate cancer; multi-parametric MR imaging; TRUS/MRI fusion tracking

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