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1.  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
3.  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
4.  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
5.  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
6.  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
7.  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
8.  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
9.  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
10.  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
11.  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
12.  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
13.  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
14.  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
15.  Prostatic abscess in a pediatric patient with Chronic Granulomatous Disease: Report of a unique case and review of the literature 
Journal of Pediatric Surgery  2012;47(2):400-403.
Chronic granulomatous disease (CGD) is a rare hereditary disease in which phagocytes have difficulty forming the superoxide radical required to kill certain pathogens. Individuals with CGD are susceptible to a specific set of infections and granulomatous lesions. We present the case of a 15 year old male with X-linked CGD who presented with unremitting cough and fevers. He had a left sided pneumonia which persisted despite home IV antibiotics. He was admitted to an outside facility for bronchoalveolar lavage to obtain cultures and polymerase chain reaction (PCR). Computed Tomography (CT) of chest, abdomen and pelvis was done for baseline evaluation of extent of disease. CT revealed a fluid collection in the prostatic fossa, later determined to be a prostatic abscess. To our knowledge, this is the first reported case of a prostatic abscess in a pediatric patient with CGD.
doi:10.1016/j.jpedsurg.2011.11.003
PMCID: PMC3282836  PMID: 22325401
Chronic granulomatous disease; CGD; prostatic abscess; pediatric patient
17.  Comprehensive microRNA Profiling of Prostate Cancer 
Journal of Cancer  2013;4(5):350-357.
MicroRNAs are small non-coding RNA molecules that have been shown to regulate the expression of genes linked to cancer. The relevance of microRNAs in the development, progression and prognosis of prostate cancer is not fully understood. It is also possible that these specific molecules may assist in the recognition of aggressive tumors and the development of new molecular targets. Our study investigated the importance of several microRNAs in cases of prostate cancer from 37 patients that were manually microdissected to obtain pure populations of tumor cells, normal epithelium and adjacent stroma. MicroRNA was extracted for PCR array profiling. Differentially expressed miRNAs for each case were used to compare tumor vs. normal epithelium and tumor-adjacent stroma samples.
Loss of 18 miRNAs (e.g.miR-34c, miR-29b, miR-212 and miR-10b) and upregulation of miR-143 and miR-146b were significantly found in all the tumors in comparison with normal epithelium and/or stroma (p≤ 0.001). A different signature was found in the high grade tumors (Gleason score ≥ 8) when compared with tumors Gleason score 6. Upregulation of miR-122, miR-335, miR-184, miR-193, miR-34, miR-138, miR-373, miR-9, miR-198, miR-144 and miR-215 and downregulation of miR-96, miR-222, miR-148, miR-92, miR-27, miR-125, miR-126, miR-27 were found in the high grade tumors.
MicroRNA profiling in prostate cancer appears to have unique expression patterns in comparison with normal tissue. These differential expressed miRNAs may provide novel diagnostic and prognostic tools that will assist in the recognition of prostate cancers with aggressive behavior.
doi:10.7150/jca.6394
PMCID: PMC3677622  PMID: 23781281
microRNA; Prostate Cancer; biomarkers.
18.  11C-Acetate PET/CT Imaging in Localized Prostate Cancer: A study with MRI and Histopathologic Correlation 
This work characterizes the uptake of 11C-Acetate in prostate cancer (PCa), benign prostate hyperplasia (BPH) and normal prostate tissue in comparison with multi-parametric MRI, whole mount histopathology and clinical markers, to evaluate its potential utility for delineating intra-prostatic tumors in a population of patients with localized PCa.
METHODS
39 men with presumed localized PCa underwent dynamic/static abdomen-pelvic 11C-Acetate PET/CT for 30-minutes and 3T multi-parametric (MP) MRI prior to prostatectomy. PET/CT images were registered to MRI using pelvic bones for initial rotation-translation, followed by manual adjustments to account for prostate motion and deformation from the MRI endorectal coil. Whole-mount pathology specimens were sectioned using an MRI-based patient specific mold resulting in improved registration between the MRI, PET and pathology. 11C-Acetate PET standardized uptake values were compared with MP-MRI and pathology.
RESULTS
11C-Acetate uptake was rapid but reversible, peaking at 3–5 minutes post-injection and reaching a relative plateau at ~10 minutes. The average SUVmax(10–12min) of tumors was significantly higher than that of normal prostate tissue (4.4±2.05, range 1.8–9.2 vs. 2.1±0.94, range 0.7–3.4; p<0.001); however it was not significantly different from benign prostatic hyperplasia (4.8±2.01; range 1.8–8.8). A sector-based comparison with histopathology, including all tumors > 0.5 cm, revealed a sensitivity and specificity of 61.6 % and 80.0 % for 11C-Acetate PET/CT, and 82.3% and 95.1% for MRI, respectively. Considering only tumors >0.9 cm the 11C-Acetate accuracy was comparable to that of MRI. In a small cohort (n=9), 11C-Acetate uptake was independent of fatty acid synthase expression based on immunohistochemistry.
CONCLUSION
11C-Acetate PET/CT demonstrates higher uptake in tumor foci than normal prostate tissue; however 11C-Acetate uptake in tumors is similar to BPH nodules. While 11C-Acetate PET/CT is not likely to have utility as an independent modality for evaluation of localized PCa, the high uptake in tumors may make it useful for monitoring focal therapy, where tissue damage after therapy may limit anatomic imaging methods.
doi:10.2967/jnumed.111.096032
PMCID: PMC3526004  PMID: 22343504
Prostate cancer; 11C-Acetate PET; Multi-parametric prostate MRI
19.  Imaging techniques for prostate cancer: implications for focal therapy 
Nature reviews. Urology  2009;6(4):191-203.
The multifocal nature of prostate cancer has necessitated whole-gland therapy in the past; however, since the widespread use of PSA screening, patients frequently present with less-advanced disease. Many men with localized disease wish to avoid the adverse effects of whole-gland therapy; therefore, focal therapy for prostate cancer is being considered as a treatment option. For focal treatment to be viable, accurate imaging is required for diagnosis, staging, and monitoring of treatment. Developments in MRI and PET have brought more attention to prostate imaging and the possibility of improving the accuracy of focal therapy. In this Review, we discuss the advantages and disadvantages of conventional methods for imaging the prostate, new developments for targeted imaging, and the possible role of image-guided biopsy and therapy for localized prostate cancer.
doi:10.1038/nrurol.2009.27
PMCID: PMC3520096  PMID: 19352394
20.  Documenting the location of systematic transrectal ultrasound-guided prostate biopsies: correlation with multi-parametric MRI 
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
21.  Partial Nephrectomy After Previous Radio Frequency Ablation: The National Cancer Institute Experience 
The Journal of Urology  2009;182(5):2158-2163.
Purpose
Development of new renal tumors or recurrence after radio frequency ablation not amendable for repeat ablation presents a difficult therapeutic dilemma. We report on the outcomes of partial nephrectomy on kidneys previously treated with radio frequency ablation.
Materials and Methods
We performed a chart review of 13 patients who underwent 16 attempted partial nephrectomies following radio frequency ablation. Hospital records and operative reports were reviewed for demographic data, perioperative data and outcomes. The outcomes of the present series were compared to historical controls of published studies in similar patient populations.
Results
No cases were converted to radical nephrectomy. Median time from radio frequency ablation to surgery was 2.75 years (range 1 to 7.1). A median of 7 tumors (range 2 to 40) were removed with a median estimated blood loss of 1,500 ml (range 500 to 3,500) and a median operative time of 7.8 hours (range 5 to 10.7). Operative notes commented on the presence of severe fibrosis in the operative field in 12 of 16 cases (75%). There was a modest but statistically significant decrease in renal function. Partial nephrectomy after radio frequency ablation had a higher reoperation rate compared to other series of primary or repeat partial nephrectomies but had the lowest rate of vascular or visceral injuries.
Conclusions
Partial nephrectomy on kidneys previously treated with radio frequency ablation is a technically challenging but feasible procedure. Residual or metachronous disease after radio frequency ablation may be salvaged with partial nephrectomy with a modest decrease in renal function. A trend toward a higher chance of reoperation and urine leak after partial nephrectomy after radio frequency ablation may be useful information for the planning and discussion of treatment decisions.
doi:10.1016/j.juro.2009.07.064
PMCID: PMC3404484  PMID: 19758659
nephrectomy; catheter ablation; treatment outcome
22.  Robot-Assisted Laparoscopic Partial Adrenalectomy for Pheochromocytoma: The National Cancer Institute Technique 
European urology  2011;60(1):118-124.
Background
Partial adrenalectomy has recently been advocated to preserve unaffected adrenal tissue during resection of pheochromocytoma.
Objective
To describe a robot-assisted laparoscopic partial adrenalectomy (RALPA) technique and to report on early functional and oncologic outcomes.
Design, setting, and participants
From 2007 to 2010, 15 RALPA were performed on 12 consecutive patients with pheochromocytoma. Follow-up data of >1 yr are available on 11 procedures. Median follow-up for the entire cohort was 17.3 mo (range: 6–45).
Surgical procedure
Positioning and port placement is designed for adequate reach and visualization of the upper retroperitoneum. The plane between the adrenal cortex and pheochromocytoma pseudocapsule is identified visually and with laparoscopic ultrasound. The tumor is dissected away from normal adrenal cortex, preserving normal adrenal tissue.
Measurements
Preoperative, perioperative, pathologic, and functional outcomes data were analyzed.
Results and limitations
Fourteen of 15 cases were completed robotically. Among 15 procedures, 4 were performed on a solitary adrenal gland. Four cases required resection of multiple tumors (up to six) with two performed in a solitary gland. The mean age of the patients was 30 yr, and the mean body mass index was 27. The mean operative time was 163 min, the median estimated blood loss was 161 ml, and the median tumor size was 2.7 cm (range: 1.3–5.5). There was one conversion to an open procedure in a patient requiring reoperation on a solitary adrenal gland. One patient who underwent RALPA on a solitary adrenal gland required postoperative steroid supplementation at last follow-up. At a median follow-up of 17.3 mo (range: 6–45), there were no recurrences or metastatic events. Study limitations include small sample size and short follow-up.
Conclusions
RALPA for the treatment of pheochromocytoma is feasible and safe and provides encouraging functional and oncologic outcomes, even in patients with a solitary adrenal lesion or multiple ipsilateral lesions.
doi:10.1016/j.eururo.2011.03.046
PMCID: PMC3109214  PMID: 21507561
Adrenalectomy; Laparoscopy; Partial adrenalectomy; Pheochromocytoma; Robotic surgery
23.  The impact of germline BHD mutation on histologic concordance and clinical management of patients with bilateral renal masses and known unilateral oncocytoma 
The Journal of urology  2011;185(6):2050-2055.
Introduction and Objective
Managing patients presenting with oncocytoma in the setting of bilateral renal masses is a challenging scenario. Nevertheless, pathologic concordance of oncocytic neoplasm in one kidney with tumors in the contralateral kidney is not known. We aim to evaluate the influence of germline Birt-Hogg-Dubé (BHD) mutation on concordance rates to assist in management of these patients.
Methods
We reviewed records of the NIH patients between 1983 and 2009 having bilateral renal masses, known pathology bilaterally, and presence of oncocytoma or oncocytic neoplasm in at least one kidney. The presence of oncocytoma or oncocytic neoplasm in two renal units was considered concordant. Demographic, pathological and clinical data were collected.
Results
The patient population consisted of 40 patients: 23 with BHD and 17 patients without diagnosis of BHD. Patients with BHD were younger (p<0.01) but there were no other differences between two groups. However, patients with BHD had a statistically lower histologic concordance between bilateral masses when compared to patients without the diagnosis of BHD (Fisher's exact test, p<0.01). Additionally, the subgroup of patients (n=8) without BHD who had multifocal renal masses demonstrated 100% oncocytoma concordance between renal units.
Conclusions
In patients with bilateral renal masses BHD patients have significantly lower histologic concordance rates compared to patients without BHD. Patients with BHD should be monitored and managed differently than patients without detected genetic mutations, especially those with multifocal oncocytomas. Genetic testing for BHD should be considered in the algorithm for management of patients with bilateral renal masses and known oncocytoma.
doi:10.1016/j.juro.2011.02.051
PMCID: PMC3164767  PMID: 21496834
oncocytoma; oncocytic tumor; Birt-Hogg-Dube; concordance; bilateral renal tumors
24.  Accelerated T2 Mapping for Characterization of Prostate Cancer 
Prostate T2 mapping was performed in 34 consecutive patients using an accelerated multi-echo spin-echo sequence with four-fold k-space undersampling leading to a net acceleration factor of 3.3 on a 3T scanner. The mean T2 values from the accelerated and conventional, unaccelerated sequences demonstrated a very high correlation (r = 0.99). Different prostate segments demonstrated similarly good interscan reproducibility (p = NS) with slightly larger difference at base: 2.0 ± 1.6 % for left base and 2.1 ± 1.1 % for right base. In patients with subsequent targeted biopsy, T2 values of histologically proven malignant tumor areas were significantly lower than the suspicious looking but non-malignant lesions (p<0.05) and normal areas (p<0.001): 100 ± 10 ms for malignant tumors, 114 ± 23 ms for suspicious lesions and 149 ± 32 ms for normal tissues. The proposed method can provide an effective approach for accelerated T2 quantification for prostate patients.
doi:10.1002/mrm.22874
PMCID: PMC3079019  PMID: 21394778
prostate cancer; k-space undersampling; T2 mapping
25.  Robot Assisted Laparoscopic Partial Adrenalectomy: Initial Experience 
Urology  2010;77(4):775-780.
Objectives
We evaluated the feasibility of performing robot assisted laparoscopic partial adrenalectomy (RALPA) in patients seen at the National Cancer Institute and report the results of our initial experience.
Methods
We reviewed the records of patients with adrenal masses who underwent attempted RALPA from July of 2008 until January of 2010. Demographic, perioperative, and pathologic data were collected. The functional and early oncologic outcomes were examined by the need for steroid replacement and development of recurrent disease, respectively.
Results
Ten patients underwent a total of 13 attempted RALPA for removal of 19 adrenal tumors. There was one open conversion with successful completion of partial adrenalectomy. Of the patients, 80% had a known hereditary syndrome predisposing them to adrenal tumors. One patient had bilateral multifocal adrenal masses with unknown germ line genetic alteration and one patient had a sporadic adrenal mass. Of the 19 tumors removed, 17 were pheochromocytoma and 2 were adrenal-cortical hyperplasia. Two patients underwent partial adrenalectomy on a solitary adrenal gland with one subsequently requiring steroid replacement post-operatively. On postoperative imaging all but one operated adrenal gland demonstrated contrast enhancement. No patient developed local recurrence at a median follow-up of 16.2 months (range 2- 29).
Conclusions
RALPA appears safe and feasible in our early experience. Only one patient in our series required steroid replacement. Local recurrence rates are low but will require longer follow up.
doi:10.1016/j.urology.2010.07.501
PMCID: PMC3074102  PMID: 21122898
Robotic; partial adrenalectomy; adrenal sparing surgery; pheochromocytoma; hereditary syndromes

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