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Natural History of Pathologically Benign Multi-parametric MRI Cancer Suspicious Regions Following MRI-Ultrasound Fusion-targeted Biopsy

Bryk, Darren J; Llukani, Elton; Huang, William C; Lepor, Herbert
PURPOSE: The objective of this study is to determine the natural history of pathologically benign multi-parametric MRI (mpMRI) cancer suspicious regions (CSR) following targeted biopsy. MATERIALS AND METHODS: Between January 2012 and September 2014, 330 men underwent prostate mpMRI. 533 CSRs were identified and scored on a Likert scale of 1-5 based on suspicion for malignancy (5=highest suspicion level). Following mpMRI, all men underwent MRI-US fusion-targeted prostate biopsy using the Profuse software and ei-Nav|Artemis system and a computer-generate 12-core random biopsy. This study analyzes a cohort of 34 men with 51 CSRs with benign prostate biopsies who underwent repeat mpMRI and PSA testing at one year. Changes in greatest linear measurement (GLM), suspicion score (ss) and serum PSA were ascertained. RESULTS: Over one year, both the ss distribution and mean GLM of the CSRs decreased significantly (p<0.0001), while mean PSA did not significantly change (p=0.632). Overall, 2 (3.9%), 15 (29.4%) and 34 (66.7%) CSRs showed an increase, no change or decrease in ss, respectively. None (0%), 21 (42.0%) and 29 (58.0%) showed an increase (>/=20%), no change or decrease (>/=20%) in GLM, respectively. Of the two CSRs exhibiting increases in ss, neither showed a PSA increase >/=0.5 ng/mL. CONCLUSIONS: Our study provides compelling evidence that few benign CSRs increase in ss and/or GLM within one year, independent of baseline ss. Therefore, routinely repeating the mpMRI at one year in men with pathologically benign CSRs should be discouraged since it is unlikely to influence management decisions.
PMID: 26003206
ISSN: 1527-3792
CID: 1603142

Comparison of Coregistration Accuracy of Pelvic Structures Between Sequential and Simultaneous Imaging During Hybrid PET/MRI in Patients with Bladder Cancer

Rosenkrantz, Andrew B; Balar, Arjun V; Huang, William C; Jackson, Kimberly; Friedman, Kent P
PURPOSE: The aim of this study was to compare coregistration of the bladder wall, bladder masses, and pelvic lymph nodes between sequential and simultaneous PET and MRI acquisitions obtained during hybrid F-FDG PET/MRI performed using a diuresis protocol in bladder cancer patients. METHODS: Six bladder cancer patients underwent F-FDG hybrid PET/MRI, including IV Lasix administration and oral hydration, before imaging to achieve bladder clearance. Axial T2-weighted imaging (T2WI) was obtained approximately 40 minutes before PET ("sequential") and concurrently with PET ("simultaneous"). Three-dimensional spatial coordinates of the bladder wall, bladder masses, and pelvic lymph nodes were recorded for PET and T2WI. Distances between these locations on PET and T2WI sequences were computed and used to compare in-plane (x-y plane) and through-plane (z-axis) misregistration relative to PET between T2WI acquisitions. RESULTS: The bladder increased in volume between T2WI acquisitions (sequential, 176 [139]mL; simultaneous, 255 [146]mL). Four patients exhibited a bladder mass, all with increased activity (SUV, 9.5-38.4). Seven pelvic lymph nodes in 4 patients showed increased activity (SUV, 2.2-9.9). The bladder wall exhibited substantially less misregistration relative to PET for simultaneous, compared with sequential, acquisitions in in-plane (2.8 [3.1]mm vs 7.4 [9.1]mm) and through-plane (1.7 [2.2]mm vs 5.7 [9.6]mm) dimensions. Bladder masses exhibited slightly decreased misregistration for simultaneous, compared with sequential, acquisitions in in-plane (2.2 [1.4]mm vs 2.6 [1.9]mm) and through-plane (0.0 [0.0]mm vs 0.3 [0.8]mm) dimensions. FDG-avid lymph nodes exhibited slightly decreased in-plane misregistration (1.1 [0.8]mm vs 2.5 [0.6]mm), although identical through-plane misregistration (4.0 [1.9]mm vs 4.0 [2.8]mm). CONCLUSIONS: Using hybrid PET/MRI, simultaneous imaging substantially improved bladder wall coregistration and slightly improved coregistration of bladder masses and pelvic lymph nodes.
PMCID:4494885
PMID: 25783514
ISSN: 0363-9762
CID: 1506152

Significance of Pathologic T3a Upstaging in Clinical T1 Renal Masses Undergoing Nephrectomy

Ramaswamy, Krishna; Kheterpal, Emil; Pham, Hai; Mohan, Sanjay; Stifelman, Michael; Taneja, Samir; Huang, William C
BACKGROUND: The objectives of the present study were to report the incidence of pathologic T3a upstaging in a contemporary cohort of patients with clinical stage T1 (cT1) renal tumors treated with partial or radical nephrectomy; investigate the clinical outcomes; and identify the predictors associated with pathologic upstaging. MATERIALS AND METHODS: From a single-institution, institutional review board-approved renal tumor database of 945 patients, we identified 610 patients who had undergone surgery for a cT1 renal mass. Data for 494 patients were available for analysis. Of these, 66 lesions had been pathologically upstaged to T3a after surgery and 428 had not. The oncologic follow-up data and clinical and pathologic features were recorded, and multivariable logistic regression analysis was performed to identify the risk factors for pT3a upstaging, controlling for age, gender, body mass index, and nephrectomy type. RESULTS: The cT1 tumors of 66 patients (13.3%) were upstaged to pT3a after surgery. Of these 66 patients, 44 (66.7%) had undergone partial and 22 (33.3%) radical nephrectomy. The median follow-up period was 50 months. No patient with upstaging developed recurrence, and all were disease free at their last follow-up visit. On multivariable analysis, tumor size > 4 cm (odds ratio [OR], 3.766; 95% confidence interval [CI], 1.417-10.011; P < .008), clear cell histologic features (OR, 4.461; 95% CI, 1.498-13.461; P < .007), and positive surgical margins (hazard ratio, 5.118; 95% CI, 2.088-12.547; P < .0001) were associated with upstaging. CONCLUSION: Of the cT1 lesions in 66 patients, 13% were pathologically upstaged after surgery. The patients with larger tumors, clear cell histologic features, and positive surgical margins were at the greatest risk of upstaging. However, after an intermediate follow-up period, pathologic upstaging did not appear to result in worsened oncologic outcomes.
PMID: 25680295
ISSN: 1938-0682
CID: 1669372

Cardiopulmonary Bypass has No Significant Impact on Survival in Patients Undergoing Nephrectomy and Level III-IV Inferior Vena Cava Thrombectomy: Multi-Institutional Analysis

Nguyen, Hao G; Tilki, Derya; Dall'Era, Marc A; Durbin-Johnson, Blythe; Carballido, Joaquin A; Chandrasekar, Thenappan; Chromecki, Thomas; Ciancio, Gaetano; Daneshmand, Siamak; Gontero, Paolo; Gonzalez, Javier; Haferkamp, Axel; Hohenfellner, Markus; Huang, William C; Linares Espinos, Estefania; Mandel, Philipp; Martinez-Salamanca, Juan I; Master, Viraj A; McKiernan, James M; Montorsi, Francesco; Novara, Giacomo; Pahernik, Sascha; Palou, Juan; Pruthi, Raj S; Rodriguez-Faba, Oscar; Russo, Paul; Scherr, Douglas S; Shariat, Shahrokh F; Spahn, Martin; Terrone, Carlo; Vergho, Daniel; Wallen, Eric M; Xylinas, Evanguelos; Zigeuner, Richard; Libertino, John A; Evans, Christopher P
PURPOSE: The impact of cardiopulmonary bypass in level III-IV tumor thrombectomy on surgical and oncologic outcomes is unknown. We determine the impact of cardiopulmonary bypass on overall and cancer specific survival, as well as surgical complication rates and immediate outcomes in patients undergoing nephrectomy and level III-IV tumor thrombectomy with or without cardiopulmonary bypass. MATERIALS AND METHODS: We retrospectively analyzed 362 patients with renal cell cancer and with level III or IV tumor thrombus from 1992 to 2012 at 22 U.S. and European centers. Cox proportional hazards models were used to compare overall and cancer specific survival between patients with and without cardiopulmonary bypass. Perioperative mortality and complication rates were assessed using logistic regression analyses. RESULTS: Median overall survival was 24.6 months in noncardiopulmonary bypass cases and 26.6 months in cardiopulmonary bypass cases. Overall survival and cancer specific survival did not differ significantly in both groups on univariate analysis or when adjusting for known risk factors. On multivariate analysis no significant differences were seen in hospital length of stay, Clavien 1-4 complication rate, intraoperative or 30-day mortality and cancer specific survival. Limitations include the retrospective nature of the study. CONCLUSIONS: In our multi-institutional analysis the use of cardiopulmonary bypass did not significantly impact cancer specific survival or overall survival in patients undergoing nephrectomy and level III or IV tumor thrombectomy. Neither approach was independently associated with increased mortality on multivariate analysis. Greater surgical complications were not independently associated with the use of cardiopulmonary bypass.
PMCID:5012645
PMID: 25797392
ISSN: 1527-3792
CID: 1693682

Management of Small Kidney Cancers in the New Millennium: Contemporary Trends and Outcomes in a Population-Based Cohort

Huang, William C; Atoria, Coral L; Bjurlin, Marc; Pinheiro, Laura C; Russo, Paul; Lowrance, William T; Elkin, Elena B
IMPORTANCE: With the significant downward size and stage migration of localized kidney cancers, the management options for small kidney cancers have expanded and evolved. OBJECTIVE: To describe trends and outcomes in the management of small kidney cancers in the first decade of the new millennium. DESIGN, SETTING, AND PARTICIPANTS: Surveillance, Epidemiology, and End Results (SEER) cancer registry data linked to Medicare claims were used to identify patients 66 years or older with a pathologically confirmed small kidney cancer (<4 cm) diagnosed between January 1, 2001, and December 31, 2009; analysis was performed between February 1, 2014, and December 31, 2014. Multivariable logistic regression was used to assess the likelihood of nonsurgical management vs surgical intervention. Cox proportional hazards regression was used to assess the relationships between treatment approach and overall and cancer-specific survival. The effect of treatment approach on cancer-specific survival was analyzed in a competing risks framework. MAIN OUTCOMES AND MEASURES: The likelihood of receiving no surgery vs surgical intervention as a function of demographic and disease characteristics, as well as the relationships between treatment approach and overall and cancer-specific survival. RESULTS: Of 6664 patients, 5994 individuals (90.0%) had surgical treatment; the care of 670 patients (10.0%) was managed nonsurgically. Use of radical nephrectomy decreased over time (from 69.0% to 42.5%), and the use of nephron-sparing surgery (partial nephrectomy and ablation) increased (from 21.5% to 49.0%); the proportion of patients who did not undergo surgery remained stable (9.5% and 8.5%). During a median follow-up of 63 months (interquartile range, 43-89 months) (follow-up for vital status through December 31, 2011), 2119 patients (31.8%) patients died, including 293 individuals (4.4%) of kidney cancer. Although overall survival was better in patients who received surgical treatment, only nephron-sparing surgery was associated with a benefit in cancer-specific survival (adjusted hazard ratio, 0.47; 95% CI, 0.31-0.69; P < .001). CONCLUSIONS AND RELEVANCE: Surgery continues to be the most common treatment for patients with small kidney cancers. The use of nephron-sparing surgery exceeds radical nephrectomy in patients who receive surgery. Although our findings suggest that nonsurgical management is acceptable for certain patients, use of this approach remains low.
PMID: 26017316
ISSN: 2168-6262
CID: 1669662

MRI features of renal cell carcinoma that predict favorable clinicopathologic outcomes

Doshi, Ankur M; Huang, William C; Donin, Nicholas M; Chandarana, Hersh
OBJECTIVE: The purpose of this article is to determine whether MRI features of renal cell carcinoma (RCC), such as enhancing solid component and T1 signal intensity, are associated with clinicopathologic outcomes. MATERIALS AND METHODS: This retrospective study included 241 RCCs in 230 patients who underwent preoperative MRI, had pathologic analysis results available, and were monitored for at least 3 months. A radiologist assessed tumor features on MRI, including unenhanced T1 signal relative to renal cortex and the percentage of solid enhancing components. The electronic medical record or follow-up images were reviewed to assess for the development of local recurrence or metastases. Statistical analysis was performed to correlate imaging features at MRI with pathologic and clinical outcome. RESULTS: The following tumor features were observed: predominantly cystic morphologic features (defined as solid component
PMID: 25794069
ISSN: 0361-803x
CID: 1506532

Subtype Differentiation of Renal Tumors Using Voxel-Based Histogram Analysis of Intravoxel Incoherent Motion Parameters

Gaing, Byron; Sigmund, Eric E; Huang, William C; Babb, James S; Parikh, Nainesh S; Stoffel, David; Chandarana, Hersh
PURPOSE: The aim of this study was to determine if voxel-based histogram analysis of intravoxel incoherent motion imaging (IVIM) parameters can differentiate various subtypes of renal tumors, including benign and malignant lesions. SUBJECTS AND METHODS: A total of 44 patients with renal tumors who underwent surgery and had histopathology available were included in this Health Insurance Portability and Accountability Act-compliant, institutional review board-approved, single-institution prospective study. In addition to routine renal magnetic resonance imaging examination performed on a 1.5-T system, all patients were imaged with axial diffusion-weighted imaging using 8 b values (range, 0-800 s/mm). A biexponential model was fitted to the diffusion signal data using a segmented algorithm to extract the IVIM parameters perfusion fraction (fp), tissue diffusivity (Dt), and pseudodiffusivity (Dp) for each voxel. Mean and histogram measures of heterogeneity (standard deviation, skewness, and kurtosis) of IVIM parameters were correlated with pathology results of tumor subtype using unequal variance t tests to compare subtypes in terms of each measure. Correction for multiple comparisons was accomplished using the Tukey honestly significant difference procedure. RESULTS: A total of 44 renal tumors including 23 clear cell (ccRCC), 4 papillary (pRCC), 5 chromophobe, and 5 cystic renal cell carcinomas, as well as benign lesions, 4 oncocytomas (Onc) and 3 angiomyolipomas (AMLs), were included in our analysis. Mean IVIM parameters fp and Dt differentiated 8 of 15 pairs of renal tumors. Histogram analysis of IVIM parameters differentiated 9 of 15 subtype pairs. One subtype pair (ccRCC vs pRCC) was differentiated by mean analysis but not by histogram analysis. However, 2 other subtype pairs (AML vs Onc and ccRCC vs Onc) were differentiated by histogram distribution parameters exclusively. The standard deviation of Dt [sigma(Dt)] differentiated ccRCC (0.362 +/- 0.136 x 10 mm/s) from AML (0.199 +/- 0.043 x 10 mm/s) (P = 0.002). Kurtosis of fp separated Onc (2.767 +/- 1.299) from AML (-0.325 +/- 0.279; P = 0.001), ccRCC (0.612 +/- 1.139; P = 0.042), and pRCC (0.308 +/- 0.730; P = 0.025). CONCLUSIONS: Intravoxel incoherent motion imaging parameters with inclusion of histogram measures of heterogeneity can help differentiate malignant from benign lesions as well as various subtypes of renal cancers.
PMID: 25387050
ISSN: 0020-9996
CID: 1348892

Impact of warm versus cold ischemia on renal function following partial nephrectomy

Eggener, Scott E; Clark, Melanie A; Shikanov, Sergey; Smith, Benjamin; Kaag, Matthew; Russo, Paul; Wheat, Jeffrey C; Wolf, J Stuart; Matin, Surena F; Huang, William C; Harel, Miriam; Cambio, Joseph; Shalhav, Arieh L; Raman, Jay D
INTRODUCTION/BACKGROUND:We evaluated renal function following partial nephrectomy with cold ischemia (CI) versus warm ischemia (WI). METHODS:Data were collected from 1,396 patients at six institutions who underwent partial nephrectomy for a renal mass with normal contralateral kidney to evaluate percent change in glomerular filtration rate (GFR) at 3-18 months. A multivariate linear regression model tested the association of percent change GFR with clinical, operative, and pathologic factors. RESULTS:A total of 874 patients (63 %) underwent PN with CI and 522 (37 %) with WI. All patients undergoing laparoscopic and robotic-assisted partial nephrectomy (n = 443) had WI, whereas 92 % of open partial nephrectomy patients (n = 953) had CI. The CI group had a lower mean baseline GFR (72 vs. 80 ml/min/1.73 m(2)), longer median ischemia time (33 vs. 29 min), and larger mean tumor size (3.2 vs. 2.9 cm) with more advanced pathologic stage (T1b-T3: 25 vs. 16 %) (all p values <0.001). Patients with CI and WI demonstrated 12.3 and 10.1 % reductions in renal function from baseline, respectively (p = 0.067). Increasing age, female gender, and increasing tumor size were associated with reduction in renal function (all p values <0.001). Neither renal hypothermia nor operative technique independently predicted reduced renal function. Sensitivity analyses limited to ischemia time >30 min, baseline estimated glomerular filtration rate <60 ml/min/1.73 m(2), or tumors >4 cm did not significantly alter the findings. CONCLUSIONS:Increasing age, female gender, and larger tumor size independently predict a decrease in renal function following partial nephrectomy with a normal contralateral kidney. Within the limitations of a non-randomized comparison, including lack of parenchymal preservation percentage, neither surgical approach (open or laparoscopic) nor presence of hypothermia appears to be associated with long-term renal function.
PMID: 24817142
ISSN: 1433-8726
CID: 5015092

Clinicopathologic Outcomes of Cystic Renal Cell Carcinoma

Donin, Nicholas M; Mohan, Sanjay; Pham, Hai; Chandarana, Hersh; Doshi, Ankur; Deng, Fang-Ming; Stifelman, Michael D; Taneja, Samir S; Huang, William C
BACKGROUND: The purpose of this study was to describe the clinicopathologic characteristics and oncologic outcomes of patients who underwent nephrectomy for cystic renal masses. PATIENTS AND METHODS: Using an institutional review board-approved database, we retrospectively reviewed the clinical, pathologic, radiologic, and oncologic outcome data of patients who received nephrectomy for a complex cystic renal mass. RESULTS: Sixty-one patients were identified who received nephrectomy for a complex cystic lesion. Average age was 64 years. Thirty-nine (64%) patients were male. At the time of resection, 1 (1.6%), 3 (4.8%), 53 (86.8%), and 4 (6.5%) had a Bosniak category II, IIF, III, and IV cystic lesion, respectively. Nineteen (31.1%) patients were initially managed expectantly but underwent surgery because of progression of complexity on follow-up. Mean pathologic tumor size was 3.3 cm (range, 0.7-12 cm). Forty-eight (78.6%) of the lesions were found to be malignant. Thirty-seven (77.1%), 5 (10.4%), 4 (8.3%), and 2 (4.1%) were stage T1a, T1b, T2a, and T3a, respectively. Clear cell was the most common histologic subtype (44%), followed by papillary (21.3%), and unclassified RCC (4.9%). With a mean and median follow-up of 48.4 and 43.0 months, respectively, no patients developed a local or metastatic recurrence. All patients were alive at last follow-up. CONCLUSION: In our series with moderate follow-up, cystic RCCs do not appear to recur or progress regardless of size, histologic subtype, or grade. These findings suggest the malignant potential of cRCCs is significantly less than solid RCCs. Further investigation is required to determine if cRCCs should be classified and managed independently from solid RCCs.
PMID: 25088469
ISSN: 1558-7673
CID: 1105172

Whole-lesion diffusion metrics for assessment of bladder cancer aggressiveness

Rosenkrantz, Andrew B; Obele, Chika; Rusinek, Henry; Balar, Arjun V; Huang, William C; Deng, Fang-Ming; Ream, Justin M
PURPOSE: To explore associations of whole-lesion histogram diffusion metrics with pathologic findings and subsequent metastatic disease in bladder cancer patients undergoing radical cystectomy. METHODS: Twenty-three bladder cancer patients (21M, 2F; mean 70 +/- 11 years) underwent MRI before cystectomy. A volume-of-interest was placed on all slices on the ADC map encompassing each lesion. Whole-lesion mean, kurtosis, and skewness of ADC were calculated and compared with T stage and pelvic nodal status at cystectomy and with subsequent metastasis in 20/25 patients with available follow-up. RESULTS: At cystectomy, 39 % (9/23) were stage T2, 61 % (14/23) >/=T3, and 28 % (5/23) exhibited positive nodes; 35 % (7/20) developed later metastases. Mean ADC was significantly lower in stage >/=T3 than in lower stage tumors (1.20 +/- 0.36 x 10-3 vs. 1.55 +/- 0.36 x 10-3 mm2/s; p = 0.044), but showed no association with nodal or metastatic disease (p = 0.362-0.709). Kurtosis was significantly lower in tumors with, compared to without, nodal disease (-0.05 +/- 0.29 vs. 0.91 +/- 1.16; p = 0.037), and showed a non-significant decrease in tumors with, compared to without, later metastases (0.23 +/- 0.63 vs. 0.83 +/- 0.89; p = 0.088). Kurtosis was not associated with T stage (p = 0.811), and skew was not associated with any outcome (p = 0.516-0.643). Mean ADC achieved highest AUC for identification of stage >/=T3 (AUC = 0.754 vs. 0.516-0.643 for other metrics). Kurtosis achieved highest AUC for nodal disease (AUC = 0.811 vs. 0.522-0.556 for other metrics) and metastases (AUC = 0.736 vs. 0.516-0.626 for other metrics). Only difference in AUC between skewness and kurtosis for nodal disease was significant (p = 0.031). CONCLUSION: While requiring larger studies, kurtosis has potential to complement mean ADC in bladder cancer prognosis using whole-lesion histogram analysis.
PMID: 25106502
ISSN: 0942-8925
CID: 1141422