Analyzing the learning curves of a novice and an experienced urologist for transrectal magnetic resonance imaging-ultrasound fusion prostate biopsy.

BACKGROUND: The aim of the current study was to evaluate and compare the learning curves of transrectal magnetic resonance imaging-ultrasound fusion biopsy for two urologists with different backgrounds (Operator 1: experienced, self-trained and Operator 2: novice, trained by a mentor/MRI reading courses). METHODS: A cohort of 400 patients who underwent fusion prostate biopsy in our department was analyzed. The learning curves were assessed in terms of overall and clinically significant prostate cancer (PCa) detection rates, percentage of positive biopsy cores/targeted and the percentage of PCa tissue on positive targeted cores. RESULTS: Increasing trends were observed for both urologists in terms of all biopsy outcomes during the study time. For the novice urologist, a significant increase was observed for overall PCa detection rate, but not for clinically significant disease (25.44%, P=0.04/15%, P=0.145). Operator 1 showed an increasing diagnosis yield of clinically significant disease up to 104 cases. Similar cancer detection rates were observed when comparing the first and last biopsies performed by both operators. Multivariate analysis adjusted for age, PSA, prostate volume, lesion diameter and PIRADS score showed an increase of PCa detection with 51% for every 52 biopsies performed (P=0.022). CONCLUSIONS: When starting with magnetic resonance imaging-ultrasound fusion prostate biopsy, mentoring and prostate magnetic resonance imaging reading training allow a novice urologist to demonstrate a good initial PCa detection rate. After about 52 cases, he reached a stable PCa and clinically significant PCa detection rate, that was similar to that of an experienced urologist.

MRI-targeted prostate biopsy: the next step forward!

AIM: For decades, the gold standard technique for diagnosing prostate cancer was the 10 to 12 core systematic transrectal or transperineal biopsy, under ultrasound guidance. Over the past years, an increased rate of false negative results and detection of clinically insignificant prostate cancer has been noted, resulting into overdiagnosis and overtreatment. The purpose of the current study was to evaluate the changes in diagnosis and management of prostate cancer brought by MRI-targeted prostate biopsy. METHODS: A critical review of literature was carried out using the Medline database through a PubMed search, 37 studies meeting the inclusion criteria: prospective studies published in the past 8 years with at least 100 patients per study, which used multiparametric magnetic resonance imaging as guidance for targeted biopsies. RESULTS: In-Bore MRI targeted biopsy and Fusion targeted biopsy outperform standard systematic biopsy both in terms of overall and clinically significant prostate cancer detection, and ensure a lower detection rate of insignificant prostate cancer, with fewer cores needed. In-Bore MRI targeted biopsy performs better than Fusion biopsy especially in cases of apical lesions. CONCLUSION: Targeted biopsy is an emerging and developing technique which offers the needed improvements in diagnosing clinically significant prostate cancer and lowers the incidence of insignificant ones, providing a more accurate selection of the patients for active surveillance and focal therapies.

Preoperative Predicting the WHO/ISUP Nuclear Grade of Clear Cell Renal Cell Carcinoma by Computed Tomography-Based Radiomics Features.

Nuclear grade is important for treatment selection and prognosis in patients with clear cell renal cell carcinoma (ccRCC). This study aimed to determine the ability of preoperative four-phase multiphasic multidetector computed tomography (MDCT)-based radiomics features to predict the WHO/ISUP nuclear grade. In all 102 patients with histologically confirmed ccRCC, the training set (n = 62) and validation set (n = 40) were randomly assigned. In both datasets, patients were categorized according to the WHO/ISUP grading system into low-grade ccRCC (grades 1 and 2) and high-grade ccRCC (grades 3 and 4). The feature selection process consisted of three steps, including least absolute shrinkage and selection operator (LASSO) regression analysis, and the radiomics scores were developed using 48 radiomics features (10 in the unenhanced phase, 17 in the corticomedullary (CM) phase, 14 in the nephrographic (NP) phase, and 7 in the excretory phase). The radiomics score (Rad-Score) derived from the CM phase achieved the best predictive ability, with a sensitivity, specificity, and an area under the curve (AUC) of 90.91%, 95.00%, and 0.97 in the training set. In the validation set, the Rad-Score derived from the NP phase achieved the best predictive ability, with a sensitivity, specificity, and an AUC of 72.73%, 85.30%, and 0.84. We constructed a complex model, adding the radiomics score for each of the phases to the clinicoradiological characteristics, and found significantly better performance in the discrimination of the nuclear grades of ccRCCs in all MDCT phases. The highest AUC of 0.99 (95% CI, 0.92-1.00, p < 0.0001) was demonstrated for the CM phase. Our results showed that the MDCT radiomics features may play a role as potential imaging biomarkers to preoperatively predict the WHO/ISUP grade of ccRCCs.

Differentiation of Clear Cell Renal Cell Carcinoma from other Renal Cell Carcinoma Subtypes and Benign Oncocytoma Using Quantitative MDCT Enhancement Parameters.

Background and objectives: The use of non-invasive techniques to predict the histological type of renal masses can avoid a renal mass biopsy, thus being of great clinical interest. The aim of our study was to assess if quantitative multiphasic multidetector computed tomography (MDCT) enhancement patterns of renal masses (malignant and benign) may be useful to enable lesion differentiation by their enhancement characteristics. Materials and Methods: A total of 154 renal tumors were retrospectively analyzed with a four-phase MDCT protocol. We studied attenuation values using the values within the most avidly enhancing portion of the tumor (2D analysis) and within the whole tumor volume (3D analysis). A region of interest (ROI) was also placed in the adjacent uninvolved renal cortex to calculate the relative tumor enhancement ratio. Results: Significant differences were noted in enhancement and de-enhancement (diminution of attenuation measurements between the postcontrast phases) values by histology. The highest areas under the receiver operating characteristic curves (AUCs) of 0.976 (95% CI: 0.924-0.995) and 0.827 (95% CI: 0.752-0.887), respectively, were demonstrated between clear cell renal cell carcinoma (ccRCC) and papillary RCC (pRCC)/oncocytoma. The 3D analysis allowed the differentiation of ccRCC from chromophobe RCC (chrRCC) with a AUC of 0.643 (95% CI: 0.555-0.724). Wash-out values proved useful only for discrimination between ccRCC and oncocytoma (43.34 vs 64.10, p < 0.001). However, the relative tumor enhancement ratio (corticomedullary (CM) and nephrographic phases) proved useful for discrimination between ccRCC, pRCC, and chrRCC, with the values from the CM phase having higher AUCs of 0.973 (95% CI: 0.929-0.993) and 0.799 (95% CI: 0.721-0.864), respectively. Conclusions: Our observations point out that imaging features may contribute to providing prognostic information helpful in the management strategy of renal masses.

Systematic sampling during MRI-US fusion prostate biopsy can overcome errors of targeting-prospective single center experience after 300 cases in first biopsy setting.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) and targeted biopsy have become an integral part of the diagnosis of prostate cancer (PCa), as recommended by the European Association of Urology Guidelines. The aim of the current study was to evaluate the performance of MRI and MRI-transrectal ultrasound (TRUS) fusion prostate biopsy as first biopsy setting in a tertiary center. METHODS: A cohort of 300 patients was included in the current analysis. All patients presented with clinical or biochemical suspicion of PCa and harbored at least one suspect lesion on mpMRI. MRI-TRUS fusion prostate biopsy, followed by 12 core systematic prostate biopsy were performed by the same operator using a rigid registration system. RESULTS: The mean age of the patients was 64 years (IQR: 58-68.5 years) and the mean PSA was 6.35 ng/mL (IQR: 4.84-9.46 ng/mL). Overall cancer and csPCa diagnosis rates were 47% and 40.66%. Overall PCa/csPCa detection rates were 20.4%/11.1%, 52%/45% and 68.5%/66.7% for PI-RADS lesions 3, 4 and 5 (P<0.001/P<0.0001). Larger lesion diameter and lesion volume were associated with PCa diagnosis (P=0.006 and P=0.001, respectively). MRI-TRUS fusion biopsy missed PCa diagnosis in 37 cases (of whom 48.6% ISUP 1) in comparison with 9 patients missed by systematic biopsy (of whom 11.1% ISUP 1). In terms of csPCa, systematic biopsy missed 77.7% of the tumors located in the anterior and transitional areas. The rate of csPCa was highest when targeted biopsy was associated with systematic biopsy: 86.52% vs. 68.79% for targeted biopsy vs. 80.14% for systematic biopsy, P=0.0004. In 60.6% of cases, systematic biopsy was positive for PCa at the same site as the targeted lesion. Of these patients, eight harbored csPCa and were diagnosed exclusively on systematic biopsy. CONCLUSIONS: MRI-TRUS fusion prostate biopsy improves the diagnosis of csPCa. The main advantage of an MRI-guided approach is the diagnosis of anterior and transitional area tumors. The best results in terms of csPCa diagnosis are obtained by the combination of MRI-TRUS fusion with systematic biopsy. The systematic biopsy performed during MRI-targeted biopsy could have an important role in overcoming errors of MRI-TRUS fusion systems.

MRI-TRUS fusion guided prostate biopsy - initial experience and assessment of the role of contralateral lobe systematic biopsy.

AIMS: To present our initial experience and results of MRI-TRUS fusion guided prostate biopsy and assess the role of contralateral lobe systematic biopsy. MATERIAL AND METHOD: A number of 119 patients with clinical or biochemical suspicion for prostate cancer (PCa) were included. All patients harbored at least one PIRADS score ≥ 3 lesion and underwent MRI-TRUS fusion guided biopsy, as well as a concurrent systematic biopsy. The biopsy was performed by the same operator, using a rigidregistration software system. RESULTS: The mean age of the patients was 62.2 years. The mean pre-biopsy PSA was 9.15 ng/dl. The diagnosis rate of MRI-TRUS fusion guided biopsy was 47% for overall PCa and 29.4% for clinically significant (cs) PCa. A higher PIRADS score was significantly associated with the presence of overall and csPCa. MRI-TRUS fusion guided biopsy had a higher percentage of positive biopsy cores (51% vs 29%), higher likelihood of csPCa (OR 5.36, p=0.008) and upgrading (14.8%) in comparison with systematic biopsy but missed 6.7% csPCa. The contralateral lobe systematic biopsy could have been avoided without losing the PCa diagnosis all patients with PIRADS score 5, both in initial and repeat biopsy setting. Anterior and transitional lesions were more likely to be diagnosed only by targeted cores. CONCLUSION: MRI-TRUS guided prostate biopsy improves the detection of PCa, but systematic biopsy is still essential. In selected cases (PIRADS 5), contralateral lobe systematic biopsy can safely be avoided. Pre-biopsy mpMRI might reduce the number of biopsy sessions in patients with anterior and transitional lesions.

Acoustic Radiation Force Impulse quantitative elastography: a new noninvasive technique for the evaluation of parotid glands. A preliminary study in controls and in patients with irradiated nasopharyngeal carcinoma.

AIM: We aim to define the values of the shear wave velocity (SWV) in the normal parotid glands (PG) and to identify the modifications of tissue stiffness in patients with irradiated nasopharyngeal carcinoma. MATERIAL AND METHODS: Sixty normal parotid glands pertaining to 30 healthy volunteers and 40 pathological parotid glands pertaining to 20 patients who had had underwent radiation therapy for nasopharyngeal carcinoma were included in this study. The patients underwent a B mode ultrasonography examination and the volume of the parotid gland was determined. A subsequent Acoustic Radiation Forde Impulse Imaging (ARFI) examination was performed and the SWV were determined for the central and the periphery of the glandular parenchyma. RESULTS: The mean volume of the gland in the volunteers' group (12.02+/-0.6 ml) was significantly higher than in the group of patients who underwent radiation therapy (10.3+/-0.74 ml) (p<0.0001). The SWV values in the normal group were lower compared to the patients group (1.54+/-0.6 m/s vs. 1.76+/-0.73 m/s, p<0.0001). CONCLUSION: Elastography using the ARFI technique constitutes an objective method used for the evaluation of glandular stiffness in both normal and post radiotherapy glands. The SWV values determined in patients who underwent head and neck radiotherapy are increased, indicating a greater tissue stiffness thereby implying a structural transformation of the glandular parenchyma.

Investigation of Renal Cell Carcinoma by Contrast-Enhanced Ultrasound- Predictive Value of Time Intensity Curve Analysis in Establishing Local Tumor Invasion and Stage: A Pilot Study.

PURPOSE: Contrast-enhanced ultrasound (CEUS) allows for real-time examination of signal intensity changes in a region of interest (ROI) and quantification of contrast agent kinetics. This study assessed the predictive ability of time-intensity curve (TIC) parameters for local tumor invasion and T stage of renal cell carcinoma (RCC). MATERIALS AND METHODS: Renal tumors in 41 patients were examined by CEUS. Thirty-two met the inclusion criteria, with a total of 33 tumors (27 clear cell, 4 chromophobe, and 2 papillary type I). Nineteen (57.6%) tumors were included in group A (stages pT1 and pT2) and 14 (42.4%) in group B (stage pT3). ROIs were established as: whole tumor (TuW); tumor area with the highest signal intensity (TuMAX) and renal cortex (Ref). The TIC param­eters for each ROI were calculated as below: peak signal intensity, time to peak (TTP), rise time (RT), and mean transit time (MTT). They were analyzed as a whole value for each ROI and as a ratio between the different ROIs. RESULTS: There were significant differences between the tumors invading and not invading the renal sinus fat for TTP (TuW/Ref) [0.98 (0.67-1.25) vs. 1.18 (1.08-1.3), P < .05]. For differentiation between groups A and B, the following ratios were proven as predictors by univariate regression analysis: TTP (TuMAX/TuW); MTT (Tu­MAX/TuW); RT (TuMAX/TuW) (P = .03, P = .01 and P = .02, respectively). The value derived from the Receiver Operating Characteristic (ROC) curve for RT (TuMAX/TuW) was 0.8 with sensitivity = 78.6%, specificity = 89.5%, and cutoff value of > 0.91. CONCLUSION: TIC parameters were predictors of locally noninvasive and invasive RCC.

Quantitative assessment of the masseter muscle's elasticity using Acoustic Radiation Force Impulse.

AIMS: The study proposes Acoustic Radiation Force Impulse (ARFI) assessment of the masseter muscle elasticity in the healthy population and in patients who have undergone head and neck radiation therapy. PATIENTS AND METHODS: Twenty-five healthy controls constituted group A, and 13 patients who had underwent radiotherapy (35Gy minimum) formed group B. ARFI was performed bilaterally in the periphery (P) and the muscle center (C), in relaxation and contraction. Means and standard deviations were obtained for the recorded shear waves velocities (SWV). RESULTS: For group A: in the relaxed right muscle C = 1.87±0.52 m/s and P = 1.96 ±0.55 m/s and in the left muscle C = 1.66 +/- 0.47 m/s, P = 1.67 +/-0.53 m/s. For group B, in relaxation, the right side presented C = 1.67 +/-0.6 m/s, P 1.72 +/-0.56 m/s, the left muscle C = 1.6 +/-0.34 m/s, P = 1.73 +/-0.37 m/s. There were no differences (p> 0.05) between P and C of both groups, regardless of the muscle state. The values for relaxation and contraction in A and B (merged values of the right and left) presented no differences (1.79+/-0.52 m/s vs 1.72 +/-0.73 m/s, p = 0.72 and 1.70 +/-0.48 m/s and vs 1.59 +/-0.77 m/s, p = 0.98). All measurements of group A vs B were not different (1.79 +/-0.52 m/s vs 1.65 +/-0.63 m/s, p = 0.78). CONCLUSIONS: ARFI with SWV measurement enables the quantification of normal and post irradiation elasticity of the masseter. Further studies on a larger population are required to validate the normal and pathologic values.

Solid parotid tumors: an individual and integrative analysis of various ultrasonographic criteria. A prospective and observational study.

OBJECTIVES: The purpose of the study is to identify and validate ultrasound criteria for parotid tumors evaluation, as well as to elaborate a multimodal, multi-criteria and integrative ultrasound approach for allowing tumor discrimination in a non-invasive manner. MATERIAL AND METHOD: Twenty patients with solid parotid tumors (12 benign, 8 malignant) were examined by ultrasound: real-time "grey scale" ultrasound, Doppler ultrasound, elastography, harmonic ultrasound imaging with i.v. contrast (CEUS). The study focused on tumor morphology and circulation. The analysis of the results was observational, enhanced by statistical methods and artificial intelligence (decision trees). RESULTS: All malignant tumors showed increased hypoechogenicity, tumoral cervical adenopathies, increased stiffness and "in block" mobility with the parotid gland upon palpation with the transducer, uneven distribution of the contrast material during the arterial phase (8/8). To varying degrees, they showed imprecise delineation (7/8), structural heterogeneity (6/8) and disorganized flow pattern (6/8). All cases of benign tumors showed heterogeneous echostructure, clear delineation and no capsule (12). They also showed moderate hypoechogenicity (9/12), no cervical lymph nodes (11/12) and variable rigidity (increased 6/12; low 3/12). A selection and ranking of relevant ultrasound parameters was also made. Some of them were included in a transparent and easy-to-use decision tree model with 100% data accuracy. CONCLUSIONS: The characterization and discrimination of solid parotid tumors require a multimodal and multicriteria approach. Ultrasound criteria can be divided into criteria of certainty and criteria of diagnosis probability. CEUS examination of parotid tumors did not reveal significant differences between benign and malignant circulatory bed. Decision trees discovered by artificial intelligence from the data may represent intelligent diagnosis support systems with very high accuracy, up to 100%.

ARFI quantitative elastography of the submandibular glands. Normal measurements and the diagnosis value of the method in radiation submaxillitis.

OBJECTIVES: Evaluation of Acoustic Radiation Force Impulse Imaging (ARFI) elastography performance in predicting the elasticity of the submandibular glands in normal situations and after radiation therapy. MATERIAL AND METHOD: A number of 54 normal submandibular glands from 27 voluntary subjects and 33 pathological submandibular glands (radiation submaxillities) from 18 patients who had undergone radiation therapy for various cervical and facial oncological conditions were included in study. All the patients had undergone a B mode ultrasonography (Tissue Harmonic Imaging, 8-14 MHz) while the submandibular volume was determined and subsequently an ARFI examination while the shear wave velocity (SWV) was measured (in the central, peripheral and subcapsular areas, with the results expressed in m/s). RESULTS: In the volunteers' group the mean value of the SWV of the left submandibular gland was 1.68 ± 0.46 m/s, determined in the centre of the gland, 1.88 ± 0.4 m/s in the periphery (corresponding to the subcapsular parenchyma) and the SWV of the right submandibular gland was 1.74 ± 0.35 m/s (centrally) and 1.84 ± 0.43 m/s in the periphery. The mean value of all measurements was 1.82 ± 0.41 m/s. The mean volume of the glands was 7.97 ± 2.63 cm3. In the group of patients who had underwent radiation therapy (at least 35Gy), the mean value of the SWV was 2.24 ± 0.49 m/s centrally and 2.1 ± 0.58 m/s in the periphery on the left and 1.99 ± 0.5 m/s centrally and 2.21 ± 0.52 m/s in the periphery on the right. The mean value of all the measurements was 2.13 ± 0.52 m/s and the mean volume of the gland was 5.95 ± 4.16 cm3. CONCLUSIONS: Elastography using ARFI technique is a valid examination in the evaluation of the normal and pathological submandibular gland stiffness. The values of the shear wave velocities that correspond to a normal stiffness, determined through the ARFI technique, are similar in the two glands. After cervical and facial radiation therapy the values of the SWV are increased, indicating a change in the consistency of the gland thus implying a structural transformation. The ARFI technique can be used in the evaluation of the salivary glands pathology.

Contrast enhanced ultrasonography (CEUS) in the characterization of tumor microcirculation. Validation of the procedure in the animal experimental model.

AIM: The aims of this study are the development of a contrast enhanced ultrasonography (CEUS) protocol for rats' evaluation and the assessment of the potential benefits of CEUS in Walker 256 tumor rats. MATERIAL AND METHOD: In the study were used 36 albino Wistar rats grafted subcutaneously with Walker 256 tumor. The implementation of the ultrasound (US) guided injection technique (30 subjects - group A) was performed between 4 to 8 weeks after implantation. The contrast agent (CA) - Sono Vue (Bracco) - was administered either into the lateral vein of the tail or directly into the heart under US guidance. The US validation, focusing on CEUS (6 subjects - group B) was realized at 4 to 6 weeks after implantation. The US procedures aimed to obtain morphological (2D), vascular (color Doppler and pulsed Doppler) and angiospecific functional data (CEUS). The Vevo 2100 equipment was used for US and Time Intensity Curves (TIC) were analyzed with Sonoliver (TomTec). The tumor specimens which were resected after the last study underwent a pathology exam. RESULTS: A number of 23 successfully CEUS explorations were performed in 17 subjects (11 in group A and 6 in group B). Nineteen rats could not be evaluated (in 8 cases the tumor was not viable; 4 subjects died during CA administration; in 4 cases the administration line could not be obtained). In group B, CEUS was performed in 6 subjects at 4 weeks after implantation and in 5 subjects at 6 weeks. The statistical analysis of the TIC parameters identified significant differences between the Time to Peak, mean Transit Time and Rise Time parameters of the muscles and those of the tumor. CONCLUSIONS: CEUS was easily implemented on the studied tumor model and is adequate for the evaluation of tumor vascularity. US guided intracardiac administration of the CA is an easy and reproducible procedure. If the examination is performed at defined time intervals it detects the alterations within the tumor circulatory bed.