Transurethral injection of autologous muscle precursor cells for treatment of female stress urinary incontinence: a prospective phase I clinical trial.

INTRODUCTION AND HYPOTHESIS: The purpose was to investigate the safety and feasibility of transurethral injections of autologous muscle precursor cells (MPCs) into the external urinary sphincter (EUS) to treat stress urinary incontinence (SUI) in female patients. METHODS: Prospective and randomised phase I clinical trial. Standardised 1-h pad test, International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), urodynamic study, and MRI of the pelvis were performed at baseline and 6 months after treatment. MPCs gained through open muscle biopsy were transported to a GMP facility for processing and cell expansion. The final product was injected into the EUS via a transurethral ultrasound-guided route. Primary outcomes were defined as any adverse events (AEs) during follow-up. Secondary outcomes were functional, questionnaire, and radiological results. RESULTS: Ten female patients with SUI grades I-II were included in the study and 9 received treatment. Out of 8 AEs, 3 (37.5%) were potentially related to treatment and treated conservatively: 1 urinary tract infection healed with antibiotics treatment, 1 dysuria and 1 discomfort at biopsy site. Functional urethral length under stress was 25 mm at baseline compared with 30 mm at 6 months' follow-up (p=0.009). ICIQ-UI-SF scores improved from 7 points at baseline to 4 points at follow-up (p=0.035). MRI of the pelvis revealed no evidence of tumour or necrosis, whereas the diameter of the EUS muscle increased from 1.8 mm at baseline to 1.9 mm at follow-up (p=0.009). CONCLUSION: Transurethral injections of autologous MPCs into the EUS for treatment of SUI in female patients can be regarded as safe and feasible. Only a minimal number of expected and easily treatable AEs were documented.

Atherosclerosis of the iliac arteries for the prediction of erectile dysfunction and epistaxis in men undergoing abdominal CT scan.

BACKGROUND: To investigate the association between erectile dysfunction (ED) as well as epistaxis (ES) in relation to the extent of iliac atherosclerosis. METHODS: In this retrospective cross-sectional study, all consecutive male patients treated at our institution from 01/2016 to 12/2020 undergoing abdominal CT scan were evaluated. Patients (n = 1272) were invited by mail to participate in the study in returning two questionnaires for the evaluation of ED (IIEF-5) and ES. Patients who returned filled-in questionnaires within a 3-month deadline were included in the study. The extent of atherosclerosis in the common iliac artery (CIA) and the internal iliac artery (IIA) was assessed by calcium scoring on unenhanced CT. Stratification of results was performed according to reported IIEF-5 scores and consequential ED groups. RESULTS: In total, 437 patients (34.4% of contacted) met the inclusion criteria. Forty-two patients did not fulfill predefined age requirements (< 75 years) and 120 patients had to be excluded as calcium scoring on nonenhanced CT was not feasible. Finally, 275 patients were included in the analysis and stratified into groups of "no-mild" (n = 146) and "moderate-severe" (n = 129) ED. The calcium score (r=-0.28, p < 0.001) and the number of atherosclerotic lesions (r=-0.32, p < 0.001) in the CIA + IIA showed a significant negative correlation to the IIEF-5 score, respectively. Patients differed significantly in CIA + IIA calcium score (difference: 167.4, p < 0.001) and number of atherosclerotic lesions (difference: 5.00, p < 0.001) when belonging to the "no-mild" vs. "moderate-severe" ED group, respectively. A multivariable regression model, after adjusting for relevant baseline characteristics, showed that the number of atherosclerotic CIA + IIA lesions was an independent predictor of ED (OR = 1.05, p = 0.036), whereas CIA + IIA calcium score was not (OR = 1.00031, p = 0.20). No relevant correlation was found between ES episodes and IIEF-5 scores (r=-0.069, p = 0.25), CIA + IIA calcium score (r=-0.10, p = 0.87) or number of atherosclerotic CIA + IIA lesions (r=-0.032, p = 0.60), respectively. CONCLUSIONS: The number of atherosclerotic lesions in the iliac arteries on nonenhanced abdominal CT scans is associated with the severity of ED. This may be used to identify subclinical cardiovascular disease and to quantify the risk for cardiovascular hazards in the future. TRIAL REGISTRATION: BASEC-Nr. 2020 - 01637.

MRI Characteristics of Pediatric Renal Tumors: A SIOP-RTSG Radiology Panel Delphi Study.

BACKGROUND: The SIOP-Renal Tumor Study Group (RTSG) does not advocate invasive procedures to determine histology before the start of therapy. This may induce misdiagnosis-based treatment initiation, but only for a relatively small percentage of approximately 10% of non-Wilms tumors (non-WTs). MRI could be useful for reducing misdiagnosis, but there is no global consensus on differentiating characteristics. PURPOSE: To identify MRI characteristics that may be used for discrimination of newly diagnosed pediatric renal tumors. STUDY TYPE: Consensus process using a Delphi method. POPULATION: Not applicable. FIELD STRENGTH/SEQUENCE: Abdominal MRI including T1- and T2-weighted imaging, contrast-enhanced MRI, and diffusion-weighted imaging at 1.5 or 3 T. ASSESSMENT: Twenty-three radiologists from the SIOP-RTSG radiology panel with ≥5 years of experience in MRI of pediatric renal tumors and/or who had assessed ≥50 MRI scans of pediatric renal tumors in the past 5 years identified potentially discriminatory characteristics in the first questionnaire. These characteristics were scored in the subsequent second round, consisting of 5-point Likert scales, ranking- and multiple choice questions. STATISTICAL TESTS: The cut-off value for consensus and agreement among the majority was ≥75% and ≥60%, respectively, with a median of ≥4 on the Likert scale. RESULTS: Consensus on specific characteristics mainly concerned the discrimination between WTs and non-WTs, and WTs and nephrogenic rest(s) (NR)/nephroblastomatosis. The presence of bilateral lesions (75.0%) and NR/nephroblastomatosis (65.0%) were MRI characteristics indicated as specific for the diagnosis of a WT, and 91.3% of the participants agreed that MRI is useful to distinguish NR/nephroblastomatosis from WT. Furthermore, all participants agreed that age influenced their prediction in the discrimination of pediatric renal tumors. DATA CONCLUSION: Although the discrimination of pediatric renal tumors based on MRI remains challenging, this study identified some specific characteristics for tumor subtypes, based on the shared opinion of experts. These results may guide future validation studies and innovative efforts. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 3.

Structured manual for MRI assessment of deep infiltrating endometriosis using the ENZIAN classification.

PURPOSE: Proposal of a systematic approach to assess Deep infiltrating endometriosis (DIE) through pelvic Magnetic resonance imaging (MRI) using the Enzian classification and examination of inter-rater agreement. METHODS: Three radiologists reviewed 23 MRI of patients with pelvic DIE at one tertiary referral center retrospectively and independently. Inclusion criteria were intraoperative confirmation of DIE and MR imaging according to ESUR (European Society of Urogenital Radiology) guidelines. Assessment of the anatomical pelvic compartments was performed using a manual based on the Enzian classification with step-by-step instructions using recommended planes and sequences presented here. Interrater agreement was measured using kappa statistics. RESULTS: According to the intraoperative site lesions in 53 anatomical compartments were present. Interrater agreement was best for compartments A (0.255) and FB (0.642). For FI (0.204) and B (0.146) it was slight, there was poor agreement for C (- 0.263), FA (- 0.022), and FO (- 0.030), respectively, and as for FU, no ureter infiltration was described. CONCLUSION: MRI as a noninvasive diagnostic tool offers essential advantages regarding classification and therapy planning for patients with DIE. However, its assessment is difficult and a more systematic approach is needed. Our proposed manual based on the Enzian classification is reproducible and could support radiologists and gynecologists.

Novel morphological and genetic features of fumarate hydratase deficient renal cell carcinoma in HLRCC syndrome patients with a tailored therapeutic approach.

The hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC) is defined by germline mutations in the fumarate hydratase (FH) gene and associated with leiomyomas and aggressive renal cell carcinomas with FH deficiency. Here, we comprehensively characterize two new patients with HLRCC syndrome on a morphological, immunohistochemical and genetic level. The patients developed aggressive HLRCC syndrome-associated RCCs, uterine leiomyomas and dermal leiomyomas. One HLRCC syndrome-associated RCC exhibited an unusual morphology with accumulation of "colloid-like" cytoplasmic inclusions, which might serve as a novel sentinel feature to trigger further testing. This case showed partially retained FH expression, initially hampering correct diagnosis. Comprehensive next-generation sequencing analyses of HLRCC syndrome-associated RCC and leiomyomas in our patients revealed divergent genetic changes in the FH gene in different tumors from the same patient. While all leiomyomas (uterine and cutaneous) showed a FH loss of heterozygosity (LOH) as a wildtype allele inactivating event, one HLRCC-RCC showed a second, undescribed NM_000143.3; c.947C>T; p.Ala316Val FH mutation accompanying the preexisting splice site mutation c.378+2T>C. In the other HLRCC syndrome-associated RCC, the FH mutation (NM_000143.3; c.462T>G; p.Asn154Lys with a somatic LOH) represents another variant of unknown significance that we link to HLRCC - and thus classify as likely pathogenic. Due to the specific diagnosis of metastatic HLRCC syndrome-associated RCC, both cases were treated in first line with bevacizumab/erlotinib and showed remarkable and long lasting responses. These findings allow new morphological and molecular insights into the biology of the HLRCC syndrome, corroborate the "second hit" hypothesis of tumor formation in HLRCC patients and may promote a distinct therapeutic approach.

External Validation and Comparison of Prostate Cancer Risk Calculators Incorporating Multiparametric Magnetic Resonance Imaging for Prediction of Clinically Significant Prostate Cancer.

PURPOSE: We sought to externally validate recently published prostate cancer risk calculators incorporating multiparametric magnetic resonance imaging to predict clinically significant prostate cancer. We also compared the performance of these calculators to that of multiparametric magnetic resonance imaging naïve prostate cancer risk calculators. MATERIALS AND METHODS: We identified men without a previous prostate cancer diagnosis who underwent transperineal template saturation prostate biopsy with fusion guided targeted biopsy between November 2014 and March 2018 at our academic tertiary referral center. Any Gleason pattern 4 or greater was defined as clinically significant prostate cancer. Predictors, which were patient age, prostate specific antigen, digital rectal examination, prostate volume, family history, previous prostate biopsy and the highest region of interest according to the PI-RADS™ (Prostate Imaging Reporting and Data System), were retrospectively collected. Four multiparametric magnetic resonance imaging prostate cancer risk calculators and 2 multiparametric magnetic resonance imaging naïve prostate cancer risk calculators were evaluated for discrimination, calibration and the clinical net benefit using ROC analysis, calibration plots and decision curve analysis. RESULTS: Of the 468 men 193 (41%) were diagnosed with clinically significant prostate cancer. Three multiparametric magnetic resonance imaging prostate cancer risk calculators showed similar discrimination with a ROC AUC significantly higher than that of the other prostate cancer risk calculators (AUC 0.83-0.85 vs 0.69-0.74). Calibration in the large showed 2% deviation from the true amount of clinically significant prostate cancer for 2 multiparametric magnetic resonance imaging risk calculators while the other calculators showed worse calibration at 11% to 27%. A clinical net benefit was observed only for 3 multiparametric magnetic resonance imaging risk calculators at biopsy thresholds of 15% or greater. None of the 6 investigated prostate cancer risk calculators demonstrated clinical usefulness against a biopsy all strategy at thresholds less than 15%. CONCLUSIONS: The performance of multiparametric magnetic resonance imaging prostate cancer risk calculators varies but they generally outperform multiparametric magnetic resonance imaging naïve prostate cancer risk calculators in regard to discrimination, calibration and clinical usefulness. External validation in other biopsy settings is highly encouraged.

Contrast media kinetics in multiparametric magnetic resonance imaging before radical prostatectomy predicts the probability of postoperative incontinence.

PURPOSE: To evaluate the role of preoperative multiparametric magnetic resonance imaging (MRI) as predictor of post-prostatectomy incontinence (PPI). METHODS: We analyzed patients who underwent robot-assisted radical prostatectomy for localized prostate cancer at our institution between July 2015 and April 2017. In these patients, we measured the perfusion quality of the pelvic floor with contrast media kinetics in the preoperative MRI of the prostate and compared the levator ani muscle (region of interest) to the surrounding pelvic muscle structures (reference). Prospectively collected questionnaires regarding urinary incontinence were then evaluated 1 year postoperatively. Outcomes were dichotomized into "continent" (ICIQ-Score = 0-5) and "incontinent" (ICIQ-Score ≥ 6). In each patient, we determined the perfusion ratio of the levator ani muscle divided by the surrounding pelvic muscle structures and compared them among the groups. RESULTS: Forty-two patients were included in the study (n = 22 in "continent", n = 20 in "incontinent" group). The median perfusion ratio from the continent group was significantly higher compared to the incontinent group (1.61 vs. 1.15; 95% CI 0.09-0.81, p = 0.015). The median perfusion ratio in "excellent" (ICIQ-Score = 0) was significantly higher than in "poor" (ICIQ-Score ≥ 11) outcomes (1.48 vs. 0.94; 95% CI 0.04-1.03, p = 0.036). Further, a higher perfusion ratio was negatively correlated with ICIQ-Score (r = - 0.33; 95% CI - 0.58 to 0.03; p = 0.031). CONCLUSIONS: Our data demonstrate a promising new strategy to predict PPI through the perfusion quality of pelvic muscle structures with contrast media kinetics. This may facilitate preoperative patient consulting and decision-making.

Manual prostate cancer segmentation in MRI: interreader agreement and volumetric correlation with transperineal template core needle biopsy.

OBJECTIVES: To assess interreader agreement of manual prostate cancer lesion segmentation on multiparametric MR images (mpMRI). The secondary aim was to compare tumor volume estimates between MRI segmentation and transperineal template saturation core needle biopsy (TTSB). METHODS: We retrospectively reviewed patients who had undergone mpMRI of the prostate at our institution and who had received TTSB within 190 days of the examination. Seventy-eight cancer lesions with Gleason score of at least 3 + 4 = 7 were manually segmented in T2-weighted images by 3 radiologists and 1 medical student. Twenty lesions were also segmented in apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) series. First, 20 volumetric similarity scores were computed to quantify interreader agreement. Second, manually segmented cancer lesion volumes were compared with TTSB-derived estimates by Bland-Altman analysis and Wilcoxon testing. RESULTS: Interreader agreement across all readers was only moderate with mean T2 Dice score of 0.57 (95%CI 0.39-0.70), volumetric similarity coefficient of 0.74 (0.48-0.89), and Hausdorff distance of 5.23 mm (3.17-9.32 mm). Discrepancy of volume estimate between MRI and TTSB was increasing with tumor size. Discrepancy was significantly different between tumors with a Gleason score 3 + 4 vs. higher grade tumors (0.66 ml vs. 0.78 ml; p = 0.007). There were no significant differences between T2, ADC, and DCE segmentations. CONCLUSIONS: We found at best moderate interreader agreement of manual prostate cancer segmentation in mpMRI. Additionally, our study suggests a systematic discrepancy between the tumor volume estimate by MRI segmentation and TTSB core length, especially for large and high-grade tumors. KEY POINTS: • Manual prostate cancer segmentation in mpMRI shows moderate interreader agreement. • There are no significant differences between T2, ADC, and DCE segmentation agreements. • There is a systematic difference between volume estimates derived from biopsy and MRI.

Dynamic contrast enhancement in prostate MRI as predictor of erectile function and recovery after radical prostatectomy.

PURPOSE: To analyze routine preoperative prostate MRI to predict erectile function (EF) before and after radical prostatectomy (RP). METHODS: Patients who underwent RP with an existing preoperative MRI including dynamic contrast-enhanced images and completed International Index of Erectile Function (IIEF-5) questionnaires at baseline and 12 months postoperative. They were divided into four erectile dysfunction (ED) groups according to preoperative IIEF-5 score. The perfusion quality was measured in the peripheral zone of the prostate by the ratio of signal increase 120 s after wash-in of contrast agent (Ratio120) in preoperative MRI and compared between the ED groups. RESULTS: Ratio120 showed differences among the preoperative ED groups (p = .020) in 97 patients. According to IIEF-5 at 12 months postoperative, 43 patients were dichotomized into "no to mild" (≥17 points) and "moderate to severe" (≤16) ED groups. Ratio120 revealed differences among the postoperative ED groups (128.84% vs. 101.95%; p = .029) and stayed an independent predictor for ED in the multivariable regression analysis (adjusted for age, nerve-sparing and preoperative IIEF-5). ROC curves demonstrated an additional diagnostic benefit. CONCLUSIONS: Preoperative MRI of the prostate may be used for the prediction of EF and postsurgical recovery after RP. This may serve as important tool in preoperative patient counseling and management of expectations.

Diagnostic Accuracy of Multiparametric MRI versus 68Ga-PSMA-11 PET/MRI for Extracapsular Extension and Seminal Vesicle Invasion in Patients with Prostate Cancer.

Background Recent studies have reported the additive value of combined gallium 68 (68Ga)-labeled Glu-urea-Lys (Ahx)-HBED-CC ligand targeting the prostate-specific membrane antigen (PSMA) (hereafter called 68Ga-PSMA-11) PET/MRI for the detection and localization of primary prostate cancer compared with multiparametric MRI. Purpose To compare the diagnostic accuracy and interrater agreement of multiparametric MRI and 68Ga-PSMA-11 PET/MRI for the detection of extracapsular extension (ECE) and seminal vesicle infiltration (SVI) in patients with prostate cancer. Materials and Methods Retrospective analysis of 40 consecutive men who underwent multiparametric MRI and 68Ga-PSMA-11 PET/MRI within 6 months for suspected prostate cancer followed by radical prostatectomy between April 2016 and July 2018. Four readers blinded to clinical and histopathologic findings rated the probability of ECE and SVI at multiparametric MRI and PET/MRI by using a five-point Likert-type scale. The prostatectomy specimen served as the reference standard. Accuracy was assessed with a multireader multicase analysis and by calculating reader-average areas under the receiver operating characteristics curve (AUCs), sensitivity, and specificity for ordinal and dichotomized data in a region-specific and patient-specific approach. Interrater agreement was assessed with the Fleiss multirater κ. Results For multiparametric MRI versus PET/MRI in ECE detection, respectively, AUC, sensitivity, and specificity in the region-specific analysis were 0.67 and 0.75 (P = .07), 28% (21 of 76) and 47% (36 of 76) (P = .09), and 94% (529 of 564) and 90% (509 of 564) (P = .007). For the patient-specific analysis, AUC, sensitivity, and specificity were 0.66 and 0.73 (P = .19), 46% (22 of 48) and 69% (33 of 48) (P = .04), and 75% (84 of 112) and 67% (75 of 112) (P = .19), respectively. For multiparametric MRI versus PET/MRI in SVI detection, respectively, AUC, sensitivity, and specificity of the region-specific analysis were 0.66 and 0.74 (P = .21), 35% (seven of 20) and 50% (10 of 20) (P = .25), and 98% (295 of 300) and 94% (282 of 300) (P < .001). For the patient-specific analysis, AUC, sensitivity, and specificity were 0.65 and 0.79 (P = .25), 35% (seven of 20) and 55% (11 of 20) (P = .20), and 98% (137 of 140) and 94% (131 of 140) (P = .07), respectively. Interrater reliability for multiparametric MRI versus PET/MRI did not differ for ECE (κ, 0.46 vs 0.40; P = .24) and SVI (κ, 0.23 vs 0.33; P = .39). Conclusion Our results suggest that gallium 68 (68Ga)-labeled Glu-urea-Lys (Ahx)-HBED-CC ligand targeting the prostate-specific membrane antigen (PSMA) (68Ga-PSMA-11) PET/MRI and multiparametric MRI perform similarly for local staging of prostate cancer in patients with intermediate-to-high-risk prostate cancer. The increased sensitivity of 68Ga-PSMA-11 PET/MRI for the detection of extracapsular disease comes at the cost of a slightly reduced specificity. © RSNA, 2019.

Pelvic MRI after induction chemotherapy and before long-course chemoradiation therapy for rectal cancer: What are the imaging findings?

OBJECTIVES: To determine the appearance of rectal cancer on MRI after oxaliplatin-based chemotherapy (ICT) and make a preliminary assessment of MRI's value in predicting response to total neoadjuvant treatment (TNT). METHODS: In this IRB-approved, HIPAA-compliant, retrospective study between 1 January 2010-20 October 2014, pre- and post-ICT tumour T2 volume, relative T2 signal intensity (rT2SI), node size, signal intensity and border characteristics were assessed in 63 patients (65 tumours) by three readers. The strength of association between the reference standard of histopathological percent tumour response and tumour volume change, rT2SI and lymph node characteristics was assessed with Spearman's correlation coefficient and Wilcoxon's rank sum test. Cox regression was used to assess association between DFS and radiological measures. RESULTS: Change in T2 volume was not associated with TNT response. Change in rT2SI showed correlation with TNT response for one reader only using selective regions of interest (ROIs) and borderline correlation with response using total volume ROI. There was a significant negative correlation between baseline and post-ICT node size and TNT response (r = -0.25, p = 0.05; r = -0.35, p = 0.005, readers 1 and 2, respectively). Both baseline and post-induction median node sizes were significantly smaller in complete responders (p = 0.03, 0.001; readers 1 and 2, respectively). Change in largest baseline node size and decrease in post-ICT node signal heterogeneity were associated with 100% tumour response (p = 0.04). Nodal sizes at baseline and post-ICT MRI correlated with DFS. CONCLUSION: In patients undergoing post-ICT MRI, tumour volume did not correlate with TNT response, but decreased lymph node sizes were significantly associated with complete response to TNT as well as DFS. Relative T2SI showed borderline correlation with TNT response. KEY POINTS: • MRI-based tumour volume after induction chemotherapy and before chemoradiotherapy did not correlate with overall tumour response at the end of all treatment. • Lymph node size after induction chemotherapy and before chemoradiotherapy was strongly associated with complete pathological response after all treatment. • Lymph node sizes at baseline and post-induction chemotherapy MRI correlated with disease-free survival.

The Influence of Background Signal Intensity Changes on Cancer Detection in Prostate MRI.

OBJECTIVE: The objective of this study was to develop a scoring system for background signal intensity changes or prostate homogeneity on prostate MRI and to assess these changes' influence on cancer detection. MATERIALS AND METHODS: This institutional review board-approved, HIPAA-compliant, retrospective study included 418 prostate MRI examinations in 385 men who subsequently underwent MRI-guided biopsy. The Likert score for suspicion of cancer assigned by the primary radiologist was extracted from the original report, and histopathologic work-up of the biopsy cores served as the reference standard. Two readers assessed the amount of changes on T2-weighted sequences and assigned a predefined prostate signal-intensity homogeneity score of 1-5 (1 = poor, extensive changes; 5 = excellent, no changes). The sensitivity and specificity of Likert scores for detection of prostate cancer and clinically significant cancer (Gleason score ≥ 3+4) were estimated in and compared between subgroups of patients with different signal-intensity homogeneity scores (≤ 2, 3, and ≥ 4). RESULTS: Interreader agreement on signal-intensity homogeneity scores was substantial (κ = 0.783). Sensitivity for prostate cancer detection increased when scores were better (i.e., higher) (reader 1, from 0.41 to 0.71; reader 2, from 0.53 to 0.73; p ≤ 0.007, both readers). In the detection of significant cancer (Gleason score ≥ 3+4), sensitivity also increased with higher signal-intensity scores (reader 1, from 0.50 to 0.82; reader 2, from 0.63 to 0.86; p ≤ 0.028), though specificity decreased significantly for one reader (from 0.67 to 0.38; p = 0.009). CONCLUSION: Background signal-intensity changes on T2-weighted images significantly limit prostate cancer detection. The proposed scoring system could improve the standardization of prostate MRI reporting and provide guidance for applying prostate MRI results appropriately in clinical decision-making.

Cystic Renal Cell Carcinoma: A Report on Outcomes of Surgery and Active Surveillance in Patients Retrospectively Identified on Pretreatment Imaging.

PURPOSE: We evaluated the outcomes of surgical intervention and active surveillance in patients diagnosed with cystic renal cell carcinoma at our hypothesized radiological cutoff of greater than 50% cystic. MATERIALS AND METHODS: We identified all 430 patients with a pathologically confirmed cystic renal mass that fit our criteria from 2000 to 2015. The 292 patients with a lack of computerized tomography, tumors less than 50% cystic on imaging, multifocal tumors and prior renal cell carcinoma were excluded from study. Patients were stratified into benign or malignant subgroups, and radiological, clinicopathological and oncologic features were determined. Univariate and multivariate associations between clinicoradiological parameters in each group were analyzed. We similarly reviewed the records of a separate cohort of patients treated with active surveillance for cystic renal cell carcinoma. RESULTS: Of the 138 identified cases of cystic renal cell carcinoma 102 (73.9%) were renal cell carcinoma and 36 (26.1%) were benign masses. Of the tumors 77.5% were Fuhrman grade 1-2, 83.4% were stage pT2 or less and 65.9% showed clear cell histology. On univariate analysis male gender, a solid component and increasing Bosniak classification were significant for malignancy. In a separate cohort we identified 38 patients on active surveillance. The growth rate was 1.0 mm per year overall and 2.3 mm per year for the solid component. At a median followup of more than 4 years in all cohorts there was no evidence of recurrence or metastasis of cystic renal cell carcinoma. CONCLUSIONS: Patients with unifocal cystic renal cell carcinoma evaluated using a standardized radiological threshold of greater than 50% cystic had an excellent prognosis on active surveillance and after surgical resection.

Differentiation of Clear Cell Renal Cell Carcinoma From Other Renal Cortical Tumors by Use of a Quantitative Multiparametric MRI Approach.

OBJECTIVE: The purpose of this study was to develop a quantitative multiparametric MRI approach to differentiating clear cell renal cell carcinoma (RCC) from other renal cortical tumors. MATERIALS AND METHODS: This retrospective study included 119 patients with 124 histopathologically confirmed renal cortical tumors who underwent preoperative MRI including DWI, contrast-enhanced, and chemical-shift sequences before nephrectomy. Two radiologists independently assessed each tumor volumetrically, and apparent diffusion coefficient values, parameters from multiphasic contrast-enhanced MRI (peak enhancement, upslope, downslope, AUC), and chemical-shift indexes were calculated. Univariate and multivariable logistic regression analyses were performed to identify parameters associated with clear cell RCC. RESULTS: Interreader agreement was excellent (intraclass correlation coefficient, 0.815-0.994). The parameters apparent diffusion coefficient (reader 1 AUC, 0.804; reader 2, 0.807), peak enhancement (reader 1 AUC, 0.629; reader 2, 0.606), and downslope (reader 1 AUC, 0.575; reader 2, 0.561) were significantly associated with discriminating clear cell RCC from other renal cortical tumors. The combination of all three parameters further increased diagnostic accuracy (reader 1 AUC, 0.889; reader 2, 0.907; both p ≤ 0.001), yielding sensitivities of 0.897 for reader 1 and 0.897 for reader 2, and specificities of 0.762 for reader 1 and 0.738 for reader 2 in the identification of clear cell RCC. With maximized sensitivity, specificities of 0.429 and 0.262 were reached for readers 1 and 2, respectively. CONCLUSION: A quantitative multiparametric approach statistically significantly improves diagnostic performance in differentiating clear cell RCC from other renal cortical tumors.

Multiparametric MRI in the assessment of response of rectal cancer to neoadjuvant chemoradiotherapy: A comparison of morphological, volumetric and functional MRI parameters.

PURPOSE: To compare morphological and functional MRI metrics and determine which ones perform best in assessing response to neoadjuvant chemoradiotherapy (CRT) in rectal cancer. MATERIALS AND METHODS: This retrospective study included 24 uniformly-treated patients with biopsy-proven rectal adenocarcinoma who underwent MRI, including diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) sequences, before and after completion of CRT. On all MRI exams, two experienced readers independently measured longest and perpendicular tumour diameters, tumour volume, tumour regression grade (TRG) and tumour signal intensity ratio on T2-weighted imaging, as well as tumour volume and apparent diffusion coefficient on DW-MRI and tumour volume and transfer constant Ktrans on DCE-MRI. These metrics were correlated with histopathological percent tumour regression in the resected specimen (%TR). Inter-reader agreement was assessed using the concordance correlation coefficient (CCC). RESULTS: For both readers, post-treatment DW-MRI and DCE-MRI volumetric tumour assessments were significantly associated with %TR; DCE-MRI volumetry showed better inter-reader agreement (CCC=0.700) than DW-MRI volumetry (CCC=0.292). For one reader, mrTRG, post-treatment T2 tumour volumetry and assessments of volume change made with T2, DW-MRI and DCE-MRI were also significantly associated with %TR. CONCLUSION: Tumour volumetry on post-treatment DCE-MRI and DW-MRI correlated well with %TR, with DCE-MRI volumetry demonstrating better inter-reader agreement. KEY POINTS: • Volumetry on post-treatment DCE-/DW-MRI sequences correlated well with histopathological tumour regression. • DCE-MRI volumetry demonstrated good inter-reader agreement. • Inter-reader agreement was higher for DCE-MRI volumetry than for DW-MRI volumetry. • DCE-MRI volumetry merits further investigation as a metric for evaluating treatment response.

Clear Cell Renal Cell Carcinoma: Associations Between CT Features and Patient Survival.

OBJECTIVE: The objective of this study was to investigate associations between CT features and survival in patients with clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: The study included 763 patients with histopathologically confirmed ccRCC who underwent preoperative contrast-enhanced CT between 1999 and 2011. Imaging features, both qualitative (cystic tumor, necrosis, tumor contact with renal sinus, renal vein invasion, peritumoral stranding, and peritumoral neovascularity) and quantitative (maximal tumor diameter and distance from the tumor to the renal sinus), were evaluated. Univariate and multivariable Cox regressions were used to assess associations of imaging features with disease-specific survival (DSS) and disease-specific progression-free survival (PFS). RESULTS: Greater tumor size and the presence of renal vein invasion on CT were associated with decreased DSS and disease-specific PFS (p < 0.05), and the presence of extensive necrosis (more than two-thirds of the tumor volume) was associated with decreased disease-specific PFS (p < 0.05); this association remained statistically significant when we controlled for pathologic tumor stage. In contrast, no disease-specific death or progression was seen in patients with purely cystic tumors. Greater distance between the tumor and the renal sinus was not statistically significantly associated with longer survival. CONCLUSION: In patients with ccRCC, observation of extensive necrosis on CT was statistically significantly associated with decreased disease-specific PFS, whereas greater tumor size and the presence of renal vein invasion on CT were statistically significantly associated with decreased DSS and disease-specific PFS. No disease progression was observed in tumors with a cystic appearance. Therefore, selected CT features could potentially aid in risk assessment for and counseling of patients with ccRCC and could provide prognostic information beyond the established tumor staging system.

Assessment of Prostate Cancer Aggressiveness by Use of the Combination of Quantitative DWI and Dynamic Contrast-Enhanced MRI.

OBJECTIVE: The objective of this study was to investigate whether the apparent diffusion coefficient (ADC) value from DWI and the forward volume transfer constant (K(trans)) value from dynamic contrast-enhanced MRI independently predict prostate cancer aggressiveness, and to determine whether the combination of both parameters performs better than either parameter alone in assessing tumor aggressiveness before treatment. MATERIALS AND METHODS: This retrospective study included 158 men with histopathologically confirmed prostate cancer who underwent 3-T MRI before undergoing prostatectomy in 2011. Whole-mount step-section pathologic maps identified 195 prostate cancer foci that were 0.5 mL or larger; these foci were then volumetrically assessed to calculate the per-tumor ADC and K(trans) values. Associations between MRI and histopathologic parameters were assessed using Spearman correlation coefficients, univariate and multivariable logistic regression, and AUCs. RESULTS: The median ADC and K(trans) values showed moderate correlation only for tumors for which the Gleason score (GS) was 4 + 4 or higher (ρ = 0.547; p = 0.042). The tumor ADC value was statistically significantly associated with all dichotomized GSs (p < 0.005), including a GS of 3 + 3 versus a GS of 3 + 4 or higher (AUC, 0.693; p = 0.001). The tumor K(trans) value differed statistically significantly only between tumors with a GS of 3 + 3 and those with a primary Gleason grade of 4 (p ≤ 0.015), and it made a statistically significant contribution only in differentiating tumors with a GS of 4 + 3 or higher (AUC, 0.711; p < 0.001) and those with a GS of 4 + 4 or higher (AUC, 0.788; p < 0.001) from lower-grade tumors. Combining ADC and K(trans) values improved diagnostic performance in characterizing tumors with a GS of 4 + 3 or higher and those with a GS of 4 + 4 or higher (AUC, 0.739 and 0.856, respectively; p < 0.01). CONCLUSION: Although the ADC value helped to differentiate between all GSs, the K(trans) value was only a benefit in characterizing more aggressive tumors. Combining these parameters improves their performance in identifying patients with aggressive tumors who may require radical treatment.

Use of DWI in the Differentiation of Renal Cortical Tumors.

OBJECTIVE: The purpose of this study was to differentiate clear cell renal cell carcinoma (RCC) from other common renal cortical tumors by use of DWI. MATERIALS AND METHODS: The study included 117 patients (mean age, 60 years) with 122 histopathologically confirmed renal cortical tumors who underwent 1.5-T MRI that included DWI before they underwent nephrectomy between 2006 and 2013. For each tumor, two radiologists independently evaluated apparent diffusion coefficient (ADC) values on the basis of a single ROI in a nonnecrotic area of the tumor and also by assessment of the whole tumor. The concordance correlation coefficient (CCC) was calculated to assess interreader agreement. The mean ADC values of clear cell RCC and every other tumor subtype were compared using an exact Wilcoxon rank sum test. RESULTS: Interreader agreement was excellent and higher in whole-tumor assessment (CCC, 0.982) than in single-ROI analysis (CCC, 0.756). For both readers, ADC values for clear cell RCC found on single-ROI assessment (2.19 and 2.08 × 10(-3) mm(2)/s) and whole-tumor assessment (2.30 and 2.32 × 10(-3) mm(2)/s) were statistically significantly higher than those for chromophobe, papillary, or unclassified RCC (p < 0.05) but were similar to those for oncocytoma found on single-ROI assessment (2.14 and 2.32 × 10(-3) mm(2)/s) and whole-tumor assessment (2.38 and 2.24 × 10(-3) mm(2)/s). ADC values were also higher for clear cell RCC than for angiomyolipoma, but the difference was statistically significant only in whole-tumor assessment (p < 0.03). CONCLUSION: ADC values were statistically significantly higher for clear cell RCC than for chromophobe, papillary, or unclassified RCC subtypes; however, differentiating clear cell RCC from oncocytoma by use of DWI remains especially challenging, because similar ADC values have been shown for these two tumor types.

Subcentimeter pulmonary nodules are not associated with disease progression in patients with renal cell carcinoma.

PURPOSE: Renal cell carcinoma most commonly metastasizes to the lung. Indeterminate pulmonary nodules develop preoperatively in half of the patients with localized renal cell carcinoma but clinical significance remains poorly defined. We determined whether the presence of indeterminate pulmonary nodules, or nodule size or number is associated with renal cell carcinoma outcomes. MATERIALS AND METHODS: We reviewed data on 1,102 patients with renal cell carcinoma in whom chest computerized tomography was done within 6 months before nephrectomy from 2002 to 2012. Patients with metastatic disease at presentation, benign tumors, pulmonary nodules greater than 2 cm or concurrent pulmonary disease were excluded, leaving 748 available for analysis. Study outcomes included lung metastasis, any distant metastasis or death from renal cell carcinoma. Cox proportional hazards models were used to assess whether the presence of indeterminate pulmonary nodules, or nodule size or number was associated with outcomes. Models were evaluated by comparing discrimination using the Harrell c-index. RESULTS: Indeterminate pulmonary nodules were present in 382 of 748 patients (51%). Median followup was 4.1 years (IQR 2.2-6.1). The presence of indeterminate pulmonary nodules was not associated with distant metastasis or death from kidney cancer. However, compared to subcm indeterminate pulmonary nodules the nodules greater than 1 cm were associated with metastatic disease after adjusting for tumor histology, stage and size (HR 2.48, 95% CI 1.08-5.68, p = 0.031). The outcome c-index increased slightly after adding nodule size to a predictive model adjusted for tumor characteristics. CONCLUSIONS: No evidence in the current study suggested that indeterminate pulmonary nodules less than 1 cm are associated with renal cell carcinoma progression, although large nodules significantly predicted metastatic disease. Patients with subcm indeterminate pulmonary nodules would be unlikely to benefit from extensive postoperative chest imaging surveillance, which should be reserved for patients with nodules greater than 1 cm.

Interreader and inter-test agreement in assessing treatment response following transarterial embolization for hepatocellular carcinoma.

PURPOSE: To evaluate interreader and inter-test agreement in applying size- and necrosis-based response assessment criteria after transarterial embolization (TAE) for hepatocellular carcinoma (HCC), applying two different methods of European Association for the Study of the Liver (EASL) criteria. METHODS: Seventy-four patients (median age, 67 years) from a prospectively accrued study population were included in this retrospective study. Four radiologists independently evaluated CT data at 2-3 (1st follow-up, FU) and 10-12 (2nd FU) weeks after TAE and assessed treatment response using size-based (WHO, RECIST) and necrosis-based (mRECIST, EASL) criteria. Enhancing tissue was bidimensionally measured (EASLmeas) and also visually estimated (EASLest). Interreader and inter-test agreements were assessed using intraclass correlation coefficient (ICC) and κ statistics. RESULTS: Interreader agreement for all response assessment methods ranged from moderate to substantial (κ = 0.578-0.700) at 1st FU and was substantial (κ = 0.716-0.780) at 2nd FU. Inter-test agreement was substantial between WHO and RECIST (κ = 0.610-0.799, 1st FU; κ = 0.655-0.782, 2nd FU) and excellent between EASLmeas and EASLest (κ = 0.899-0.918, 1st FU; κ = 0.843-0.877, 2nd FU). CONCLUSION: Size- and necrosis-based criteria both show moderate to excellent interreader agreement in evaluating treatment response after TAE for HCC. Inter-test agreement regarding EASLmeas and EASLest was excellent, suggesting that either may be used. KEY POINTS: • Applying EASL criteria, visual estimation and bidimensional measurements show comparable interreader agreement. • EASL meas and EASL est show substantial interreader agreement for treatment response in HCC. • Agreement was excellent for EASL meas and EASL est after TAE of HCC. • Visual estimation of enhancement is adequate to assess treatment response of HCC.