Interactive Explainable Deep Learning Model Informs Prostate Cancer Diagnosis at MRI.

Background Clinically significant prostate cancer (PCa) diagnosis at MRI requires accurate and efficient radiologic interpretation. Although artificial intelligence may assist in this task, lack of transparency has limited clinical translation. Purpose To develop an explainable artificial intelligence (XAI) model for clinically significant PCa diagnosis at biparametric MRI using Prostate Imaging Reporting and Data System (PI-RADS) features for classification justification. Materials and Methods This retrospective study included consecutive patients with histopathologic analysis-proven prostatic lesions who underwent biparametric MRI and biopsy between January 2012 and December 2017. After image annotation by two radiologists, a deep learning model was trained to detect the index lesion; classify PCa, clinically significant PCa (Gleason score ≥ 7), and benign lesions (eg, prostatitis); and justify classifications using PI-RADS features. Lesion- and patient-based performance were assessed using fivefold cross validation and areas under the receiver operating characteristic curve. Clinical feasibility was tested in a multireader study and by using the external PROSTATEx data set. Statistical evaluation of the multireader study included Mann-Whitney U and exact Fisher-Yates test. Results Overall, 1224 men (median age, 67 years; IQR, 62-73 years) had 3260 prostatic lesions (372 lesions with Gleason score of 6; 743 lesions with Gleason score of ≥ 7; 2145 benign lesions). XAI reliably detected clinically significant PCa in internal (area under the receiver operating characteristic curve, 0.89) and external test sets (area under the receiver operating characteristic curve, 0.87) with a sensitivity of 93% (95% CI: 87, 98) and an average of one false-positive finding per patient. Accuracy of the visual and textual explanations of XAI classifications was 80% (1080 of 1352), confirmed by experts. XAI-assisted readings improved the confidence (4.1 vs 3.4 on a five-point Likert scale; P = .007) of nonexperts in assessing PI-RADS 3 lesions, reducing reading time by 58 seconds (P = .009). Conclusion The explainable AI model reliably detected and classified clinically significant prostate cancer and improved the confidence and reading time of nonexperts while providing visual and textual explanations using well-established imaging features. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Chapiro in this issue.

Introducing the Node Reporting and Data System 1.0 (Node-RADS): a concept for standardized assessment of lymph nodes in cancer.

"Node-RADS" addresses the lack of consensus in the radiologic assessment of lymph node involvement by cancer and meets the increasing demand for structured reporting on the likelihood of disease involvement. Node Reporting and Data System 1.0 (Node-RADS) systematically classifies the degree of suspicion of lymph node involvement based on the synthesis of established imaging findings. Straightforward definitions of imaging findings for two proposed scoring categories "size" and "configuration" are combined into assessment categories between 1 ("very low likelihood") and 5 ("very high likelihood"). This scoring system is suitable for assessing likely involvement of lymph nodes on CT and MRI scans. It can be applied at any anatomical site, and to regional and non-regional lymph nodes in relation to a primary tumor location. Node-RADS will improve communication with referring physicians and promote the consistency of reporting for primary staging and in response assessment settings. KEY POINTS: • Node-RADS standardizes reporting of possible cancer involvement of regional and distant lymph nodes on CT and MRI. • Node-RADS proposes the scoring categories "size" and "configuration" for assigning the 5-point Node-RADS score from 1 ("very low likelihood") to 5 ("very high likelihood"). • Node-RADS aims to increase consensus among radiologists for primary staging and in response assessment settings.

Validation of the PI-RADS language: predictive values of PI-RADS lexicon descriptors for detection of prostate cancer.

OBJECTIVES: To assess the discriminatory power of lexicon terms used in PI-RADS version 2 to describe MRI features of prostate lesions. METHODS: Four hundred fifty-four patients were included in this retrospective, institutional review board-approved study. Patients received multiparametric (mp) MRI and subsequent prostate biopsy including MRI/transrectal ultrasound fusion biopsy and 10-core systematic biopsy. PI-RADS lexicon terms describing lesion characteristics on mpMRI were assigned to lesions by experienced readers. Positive and negative predictive values (PPV, NPV) of each lexicon term were assessed using biopsy results as a reference standard. RESULTS: From a total of 501 lesions, clinically significant prostate cancer (csPCa) was present in 175 lesions (34.9%). Terms related to findings of restricted diffusion showed PPVs of up to 52.0%/43.9% and NPV of up to 91.8%/89.7% (peripheral zone or PZ/transition zone or TZ). T2-weighted imaging (T2W)-related terms showed a wide range of predictive values. For PZ lesions, high PPVs were found for "markedly hypointense," "lenticular," "lobulated," and "spiculated" (PPVs between 67.2 and 56.7%). For TZ lesions, high PPVs were found for "water-drop-shaped" and "erased charcoal sign" (78.6% and 61.0%). The terms "encapsulated," "organized chaos," and "linear" showed to be good predictors for benignity with distinctively low PPVs between 5.4 and 6.9%. Most T2WI-related terms showed improved predictive values for TZ lesions when combined with DWI-related findings. CONCLUSIONS: Lexicon terms with high discriminatory power were identified (e.g., "markedly hypointense," "water-drop-shaped," "organized chaos"). DWI-related terms can be useful for excluding TZ cancer. Combining T2WI- with DWI findings in TZ lesions markedly improved predictive values. KEY POINTS: • Lexicon terms describing morphological and functional features of prostate lesions on MRI show a wide range of predictive values for prostate cancer. • Some T2-related terms have favorable PPVs, e.g., "water-drop-shaped" and "organized chaos" while others show less distinctive predictive values. DWI-related terms have noticeable negative predictive values in TZ lesions making DWI feature a useful tool for exclusion of TZ cancer. • Combining DWI- and T2-related lexicon terms for assessment of TZ lesions markedly improves PPVs. Most T2-related lexicon terms showed a significant decrease in PPV when combined with negative findings for "DW hyperintensity."

Diagnostic performance of tomoelastography of the liver and spleen for staging hepatic fibrosis.

OBJECTIVES: To determine the diagnostic performance, cut-off values, and optimal drive frequency range for staging hepatic fibrosis using tomoelastography by multifrequency MR elastography of the liver and spleen. METHODS: This prospective study consecutively enrolled a total of 61 subjects between June 2014 and April 2017: 45 patients with chronic liver disease and proven stage of fibrosis and 16 healthy volunteers. Tomoelastography was performed at 1.5 T using six drive frequencies from 35 to 60 Hz. Cut-off values and AUC were calculated. Shear wave speed (in m/s) of the liver and spleen was assessed separately and in combination as a surrogate of stiffness. RESULTS: For compound multifrequency processing of the liver, cut-off and AUC values by fibrosis stage were as follows: F1, 1.52 m/s and 0.89; F2, 1.55 m/s and 0.94; F3, 1.67 m/s and 0.98; and F4, 1.72 m/s and 0.98. Diagnostic performance of the best single drive frequencies (45 Hz, 55 Hz, 60 Hz) was similar (mean AUC = 0.95, respectively). Combined analysis of the liver and spleen slightly improved performance at 60 Hz in F4 patients (mean AUC = 0.97 vs. 0.95, p = 0.03). Full-field-of-view elastograms displayed not only the liver and spleen but also small anatomical structures including the pancreas and major vessels. CONCLUSION: Tomoelastography provides full-field-of-view elastograms with unprecedented detail resolution and excellent diagnostic accuracy for staging hepatic fibrosis. Our analysis of single-frequency tomoelastography suggests that scan time can be further reduced in future studies, making tomoelastography easier to implement in clinical routine. KEY POINTS: • Tomoelastography provides full-field-of-view elastograms of the abdomen with unprecedented detail resolution and excellent diagnostic accuracy for staging hepatic fibrosis. • Diagnostic performance of single-frequency tomoelastography at higher frequencies (45 Hz, 55 Hz, 60 Hz) and compound multifrequency processing are equivalent for staging hepatic fibrosis. • Combined assessment of hepatic and splenic stiffness slightly improves diagnostic performance for staging hepatic fibrosis.

Accuracy of various criteria for lymph node staging in ductal adenocarcinoma of the pancreatic head by computed tomography and magnetic resonance imaging.

BACKGROUND: Lymph node staging of ductal adenocarcinoma of the pancreatic head (PDAC) by cross-sectional imaging is limited. The aim of this study was to determine the diagnostic accuracy of expanded criteria in nodal staging in PDAC patients. METHODS: Sixty-six patients with histologically confirmed PDAC that underwent primary surgery were included in this retrospective IRB-approved study. Cross-sectional imaging studies (CT and/or MRI) were evaluated by a radiologist blinded to histopathology. Number and size of lymph nodes were measured (short-axis diameter) and characterized in terms of expanded morphological criteria of border contour (spiculated, lobulated, and indistinct) and texture (homogeneous or inhomogeneous). Sensitivities and specificities were calculated with histopathology as a reference standard. RESULTS: Forty-eight of 66 patients (80%) had histologically confirmed lymph node metastases (pN+). Sensitivity, specificity, and Youden's Index for the criterion "size" were 44.2%, 82.4%, and 0.27; for "inhomogeneous signal intensity" 25.6%, 94.1%, and 0.20; and for "border contour" 62.7%, 52.9%, and 0.16, respectively. There was a significant association between the number of visible lymph nodes on preoperative CT and lymph node involvement (pN+, p = 0.031). CONCLUSION: Lymph node staging in PDAC is mainly limited due to low sensitivity for detection of metastatic disease. Using expanded morphological criteria instead of size did not improve regional nodal staging due to sensitivity remaining low. Combining specific criteria yields improved sensitivity with specificity and PPV remaining high.

DCE-MR imaging of orbital lesions: diagnostic performance of the tumor flow residence time τ calculated by a multi-compartmental pharmacokinetic tumor model based on individual factors.

BACKGROUND: Differentiating benign from malignant orbital lesions by imaging and clinical presentation can be challenging. PURPOSE: To differentiate benign from malignant orbital masses using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) based on tumor flow residence time τ calculated with the aid of a pharmacokinetic tumor model. MATERIAL AND METHODS: Sixty patients with orbital masses were investigated by 3-T MRI including dynamic sequences. The signal intensity-time curve after i.v. contrast medium administration within lesions was approximated by Gd-concentration profiles on the basis of model calculations where the tumor is embedded in a whole-body kinetic model. One output of the model was tumor flow residence time τ, defined as the ratio of the tumor volume and the tumor blood flow rate. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic performance of τ. The results were compared with those of Ktrans, kep, ve, iAUC, and ADC. RESULTS: Thirty-one benign and 29 malignant orbital masses were identified (reference standard: histopathology, clinical characteristics). Mean τ was significantly longer for benign masses (94 ± 48 s) than for malignant masses (21 ± 19 s, P < 0.001). ROC analysis revealed the highest area under the curve (AUC = 0.94) for τ in orbital masses compared to standard methods. CONCLUSION: Tumor flow residence times τ of benign and malignant orbital masses are valuable in the diagnostic work-up of orbital tumors. Measures of diagnostic accuracy were superior for τ compared to ADC, Ktrans, ve, and iAUC.

Tomoelastography of the prostate using multifrequency MR elastography and externally placed pressurized-air drivers.

PURPOSE: To demonstrate the feasibility of in vivo multifrequency magnetic resonance elastography (MRE) of the prostate using externally placed drivers. METHODS: Three pressurized-air drivers were used to excite shear waves within the prostate at vibration frequencies of 60, 70, and 80 Hz. Full 3D wave fields were acquired by multislice spin-echo echo-planar imaging in conjunction with tomoelastography wave speed recovery for generating full field-of-view stiffness maps. Twelve healthy volunteers were repeatedly scanned to analyze test-retest reproducibility. Five patients with suspected prostate cancer were investigated to demonstrate the clinical feasibility of the method. RESULTS: In healthy volunteers, the shear wave speed of the entire prostate was 2.24 ± 0.20 m/s with a repeatability coefficient of 0.14 m/s and 88% intraclass correlation coefficient. No significant difference between the peripheral zone (2.27 ± 0.20 m/s) and the central gland (2.22 ± 0.23 m/s) was observed. In patients, wave-speed maps displayed stiff regions consistent with the localization of suspicious masses detected by other imaging markers. CONCLUSIONS: The proposed method provides reproducible quantitative maps of tissue stiffness throughout the pelvic region and can easily be integrated into clinical imaging protocols. Clinical stiffness maps display many details of potential interest for cancer diagnosis. Magn Reson Med 79:1325-1333, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Validation of Prostate Imaging Reporting and Data System Version 2 for the Detection of Prostate Cancer.

PURPOSE: The second version of the PI-RADS™ (Prostate Imaging Reporting and Data System) was introduced in 2015 to standardize the interpretation and reporting of prostate multiparametric magnetic resonance imaging. Recently low cancer detection rates were reported for PI-RADS version 2 category 4 lesions. Therefore the aim of the study was to evaluate the cancer detection rate of PI-RADS version 2 in a large prospective cohort. MATERIALS AND METHODS: The study included 704 consecutive men with primary or prior negative biopsies who underwent magnetic resonance imaging/ultrasound fusion guided targeted biopsy and 10-core systematic prostate biopsy between September 2015 and May 2017. All lesions were rated according to PI-RADS version 2 and lesions with PI-RADS version 2 category 3 or greater were biopsied. An ISUP (International Society of Urological Pathology) score of 2 or greater (ie Gleason 3 + 4 or greater) was defined as clinically significant prostate cancer. RESULTS: The overall cancer detection rate of PI-RADS version 2 categories 3, 4 and 5 was 39%, 72% and 91% for all prostate cancer, and 23%, 49% and 77% for all clinically significant prostate cancer, respectively. If only targeted biopsy had been performed, 59 clinically significant tumors (16%) would have been missed. The PI-RADS version 2 score was significantly associated with the presence of prostate cancer (p <0.001), the presence of clinically significant prostate cancer (p <0.001) and the ISUP grade (p <0.001). CONCLUSIONS: PI-RADS version 2 is significantly associated with the presence of clinically significant prostate cancer. The cancer detection rate of PI-RADS version 2 category 4 lesions was considerably higher than previously reported. When performing targeted biopsy, the combination with systematic biopsy still provides the highest detection of clinically significant prostate cancer.

Primary magnetic resonance imaging/ultrasonography fusion-guided biopsy of the prostate.

OBJECTIVE: To examine the performance of a primary magnetic resonance imaging (MRI)/ultrasonography (US) fusion-guided targeted biopsy (TB), and in combination with an added systematic biopsy (SB). PATIENTS AND METHODS: Analysis of 318 consecutive biopsy-naïve men with suspicious multiparametric MRI (mpMRI; Prostate Imaging Reporting and Data System [PI-RADS] score ≥3) undergoing transrectal TB and 10-core SB between January 2012 and December 2016. The indication for performing mpMRI was based on clinical parameters and decided by the treating urologist before admission. TB was performed with a sensor-based MRI/US fusion-guided platform. Clinically significant prostate cancer was defined as Gleason score ≥4 + 3 = 7 (International Society of Urological Pathology Grade [ISUP] grade 3) or maximum cancer core length of ≥6 mm. RESULTS: A median (interquartile range) of 14 (13-14) biopsies per case were taken. The overall cancer detection rate (CDR) was 77% (245/318). The TB alone detected 67% of prostate cancers and the SB alone detected 70%. The PI-RADS dependent CDR for the combination of TB/SB were 38% (21/55), 78% (120/154) and 95% (104/109) for PI-RADS scores of 3/4/5, respectively. Clinically significant prostate cancer was diagnosed by the combination of TB and SB in 195 men (61%) and by TB alone in 163 cases (51%). The number of missed or underestimated prostate cancers with a Gleason score ≥8 for TB alone was 31 (10%, P < 0.001) and 21 (7%, P < 0.001) for SB alone in comparison with the results of the combination of TB and SB. The rate of insignificant prostate cancer was comparable for the combination of TB and SB and TB alone (50/318, 16% vs 50/318, 16%). CONCLUSIONS: Pre-biopsy mpMRI is of incremental value in increasing the detection of clinically significant prostate cancer in biopsy-naïve patients with suspicion of prostate cancer. Combining TB with SB further improved the diagnostic accuracy without increasing the rate of insignificant prostate cancer.

Rate of individuals with clearly increased radiosensitivity rise with age both in healthy individuals and in cancer patients.

BACKGROUND: The question of an age dependence of individual radiosensitivity has only marginally been studied so far. Therefore, we analyzed blood samples of healthy individuals and cancer patients of different ages to determine individual radiosensitivity. METHODS: Ex vivo irradiated blood samples of 595 individuals were tested. Chromosomes 1, 2 and 4 were stained by 3-color fluorescence in situ hybridization and aberrations were analyzed. Radiosensitivity was determined by the mean breaks per metaphase (B/M). RESULTS: Healthy individuals (mean age 50.7 years) had an average B/M value of 0.42 ± 0.104 and an increase of 0.0014B/M per year. The patients (mean age 60.4 years) had an average B/M value of 0.44 ± 0.150 and radiosensitivity did not change with age. In previous studies we found that from a value of 0.6B/M on an individual is considered to be distinctly radiosensitive. The portion of radiosensitive individuals (B/M > 0.6) increased in both cohorts with age. CONCLUSION: Individual radiosensitivity rises continuously with age, yet with strong interindividual variation. No age related increase of radiosensitivity can be demonstrated in patients due to the strong interindividual variation. However among old cancer patients there is a higher probability to have patients with clearly increased radiosensitivity than at younger age.

Thin-film filter wavelength-stabilized, grating combined, high-brightness kW-class direct diode laser.

We report on kW-class dense wavelength beam combining of a laser diode module consisting of ten broad-area laser diode bars by using a novel multi-laser cavity approach based on a thin-film filter (TFF) as a dispersive optical element. The wavelength-stabilized output of the TFF cavity is beam combined upon a -1st order transmission grating. Hereby, a cylindrical telescope is used for linear dispersion-matching between the TFF and the combiner grating. On the basis of simulations of the resulting beam quality deterioration, we are able to optimize the cavity and the combiner setup for optimal beam quality preservation. We demonstrate a highly efficient direct diode laser with 1.1-kW output power and a symmetrical beam parameter product of about 6mm × mrad (95 % power content) in both beam axis.

The addition of a sagittal image fusion improves the prostate cancer detection in a sensor-based MRI /ultrasound fusion guided targeted biopsy.

BACKGROUND: To explore the diagnostic benefit of an additional image fusion of the sagittal plane in addition to the standard axial image fusion, using a sensor-based MRI/US fusion platform. METHODS: During July 2013 and September 2015, 251 patients with at least one suspicious lesion on mpMRI (rated by PI-RADS) were included into the analysis. All patients underwent MRI/US targeted biopsy (TB) in combination with a 10 core systematic prostate biopsy (SB). All biopsies were performed on a sensor-based fusion system. Group A included 162 men who received TB by an axial MRI/US image fusion. Group B comprised 89 men in whom the TB was performed with an additional sagittal image fusion. RESULTS: The median age in group A was 67 years (IQR 61-72) and in group B 68 years (IQR 60-71). The median PSA level in group A was 8.10 ng/ml (IQR 6.05-14) and in group B 8.59 ng/ml (IQR 5.65-12.32). In group A the proportion of patients with a suspicious digital rectal examination (DRE) (14 vs. 29%, p = 0.007) and the proportion of primary biopsies (33 vs 46%, p = 0.046) were significantly lower. The rate of PI-RADS 3 lesions were overrepresented in group A compared to group B (19 vs. 9%; p = 0.044). Classified according to PI-RADS 3, 4 and 5, the detection rates of TB were 42, 48, 75% in group A and 25, 74, 90% in group B. The rate of PCa with a Gleason score ≥7 missed by TB was 33% (18 cases) in group A and 9% (5 cases) in group B; p-value 0.072. An explorative multivariate binary logistic regression analysis revealed that PI-RADS, a suspicious DRE and performing an additional sagittal image fusion were significant predictors for PCa detection in TB. 9 PCa were only detected by TB with sagittal fusion (sTB) and sTB identified 10 additional clinically significant PCa (Gleason ≥7). CONCLUSION: Performing an additional sagittal image fusion besides the standard axial fusion appears to improve the accuracy of the sensor-based MRI/US fusion platform.

Is the Ellipsoid Formula the New Standard for 3-Tesla MRI Prostate Volume Calculation without Endorectal Coil?

Prostate volume in multiparametric MRI (mpMRI) is of clinical importance. For 3-Tesla mpMRI without endorectal coil, there is no distinctive standard for volume calculation. We tested the accuracy of the ellipsoid formula with planimetric volume measurements as reference and investigated the correlation of gland volume and cancer detection rate on MRI/ultrasound (MRI/US) fusion-guided biopsy. One hundred forty-three patients with findings on 3-Tesla mpMRI suspicious of cancer and subsequent MRI/US fusion-guided targeted biopsy and additional systematic biopsy were analyzed. T2-weighted images were used for measuring the prostate diameters and for planimetric volume measurement by a segmentation software. Planimetric and calculated prostate volumes were compared with clinical data. The median prostate volume was 48.1 ml (interquartile range (IQR) 36.9-62.1 ml). Volume calculated by the ellipsoid formula showed a strong concordance with planimetric volume, with a tendency to underestimate prostate volume (median volume 43.1 ml (IQR 31.2-58.8 ml); r = 0.903, p < 0.001). There was a moderate, significant inverse correlation of prostate volume to a positive biopsy result (r = -0.24, p = 0.004). The ellipsoid formula gives sufficient approximation of prostate volume on 3-Tesla mpMRI without endorectal coil. It allows a fast, valid volume calculation in prostate MRI datasets.

Predictive Parameters Identifying Men Eligible for a Sole MRI/Ultrasound Fusion-Guided Targeted Biopsy without an Additional Systematic Biopsy.

OBJECTIVE: Evaluating the predictive factors that enable identifying men in which a sole MRI/ultrasound (MRI/US) fusion-guided targeted biopsy (TB) detects the maximal prostate cancer (PCa) risk group. PATIENTS AND METHODS: Retrospective analysis of 251 consecutive patients who received a sensor-based, real-time MRI/US TB in combination with a 10-core systematic biopsy (SB) between August 2013 and July 2015. Univariate and multivariate binary regression analyses were performed to evaluate the predictors for equal/superior detection of the PCa risk group by TB compared to SB. RESULTS: TB detected PCa in 63% (157/251); SB detected PCa in 70% (176/251); a combination of TB and SB detected PCa in 77% (193/251) of cancer patients. Fifty percent (291/584) of TB cores and 22% (539/2,486) of SB cores showed PCa. Predictors for equal/superior performance of a sole TB were lesion size (maximal diameter; OR 1.050, 95% CI 1.002-1.101, p = 0.043), suspicious digital rectal examination (DRE; OR 2.448, 95% CI 1.062-5.645, p = 0.036) and free/total prostate-specific antigen (PSA) ratio (f/t PSA ratio) ≤0.15 (OR 0.916, 95% CI 0.867-0.967, p = 0.002) on univariate regression analysis and f/t PSA ratio ≤0.15 (OR 0.916, 95% CI 0.867-0.967, p = 0.002) on multivariate regression analysis. CONCLUSION: The maximal axial diameter of the Prostate Imaging Reporting and Data System-lesion and f/t PSA ratio and a suspicious DRE are possible selection criteria for men eligible for a sole MRI/US fusion-guided targeted prostate biopsy.

Abdominal Wall Endometriosis: Myofibroblasts as a Possible Evidence of Metaplasia: A Case Report.

In this study, we report about a patient with extra-uterine endometriosis (EM) in the abdominal wall muscle with evident metaplasia based on the abundant alpha smooth muscle actin (ASMA)-expressing myofibroblasts. Laparotomy excision of the abdominal wall EM was done following ultrasonographic evidence of a hypodense swelling in the right rectus abdominis, which was confirmed by MRI. Immunohistochemistry staining for ASMA and collagen I was done, with the results confirming that endometriotic stromal cells expressed both. Anterior abdominal wall endometriosis was suspected because of the patient's history of recurrent EM combined with the cyclic nature of symptoms. MRI is useful in determining the extent of the disease. In case of persisting symptoms even under hormonal treatment, surgical excision is mandatory. The expression of both ASMA and collagen I in and around EM lesions supports the notion of the metaplastic process in the course of disease development.

Prostate cancer detection on transrectal ultrasonography-guided random biopsy despite negative real-time magnetic resonance imaging/ultrasonography fusion-guided targeted biopsy: reasons for targeted biopsy failure.

OBJECTIVE: To examine the value of additional transrectal ultrasonography (TRUS)-guided random biopsy (RB) in patients with negative magnetic resonance imaging (MRI)/ultrasonography (US) fusion-guided targeted biopsy (TB) and to identify possible reasons for TB failure. PATIENTS AND METHODS: We conducted a subgroup analysis of 61 men with prostate cancer (PCa) detected by 10-core RB but with a negative TB, from a cohort of 408 men with suspicious multiparametric magnetic resonance imaging (mpMRI) between January 2012 and January 2015. A consensus re-reading of mpMRI results (using Prostate Imaging Reporting and Data System [PI-RADS] versions 1 and 2) for each suspicious lesion was performed, with the image reader blinded to the biopsy results, followed by an unblinded anatomical correlation of the lesion on mpMRI to the biopsy result. The potential reasons for TB failure were estimated for each lesion. We defined clinically significant PCa according to the Epstein criteria and stratified patients into risk groups according to the European Association of Urology guidelines. RESULTS: Our analysis showed that RB detected significant PCa in 64% of patients (39/61) and intermediate-/high-risk PCa in 57% of patients (35/61). The initial mpMRI reading identified 90 suspicious lesions in the cohort. Blinded consensus re-reading of the mpMRI led to PI-RADS score downgrading of 45 lesions (50%) and upgrading of 13 lesions (14%); thus, negative TB could be explained by falsely high initial PI-RADS scores for 32 lesions (34%) and sampling of the target lesion by RB in the corresponding anatomical site for 36 out of 90 lesions (40%) in 35 of 61 patients (57%). Sampling of the target lesion by RB was most likely for lesions with PI-RADS scores of 4/5 and Gleason scores (GS) of ≥7. A total of 70 PCa lesions (67% with GS 6) in 44 patients (72%) were sampled from prostatic sites with no abnormalities on mpMRI. CONCLUSION: In cases of TB failure, RB still detected a high rate of significant PCa. The main reason for a negative TB was a TB error, compensated for by positive sampling of the target lesion by the additional RB, and the second reason for TB failure was a falsely high initial PI-RADS score. The challenges that arise for both MRI diagnostics and prostate lesion sampling are evident in our data and support the integration of RB into the TB workflow.

The detection of significant prostate cancer is correlated with the Prostate Imaging Reporting and Data System (PI-RADS) in MRI/transrectal ultrasound fusion biopsy.

PURPOSE: To evaluate the performance of real-time MRI/ultrasound (MRI/US) fusion-guided targeted biopsy (TB) in men with primary and repeat biopsies and correlate the prostate cancer detection rate (CDR) with the PI-RADS score. METHODS: Analysis included 408 consecutive men with primary and prior negative biopsies who underwent TB and 10-core random biopsy (RB) between January 2012 and January 2015. TB was performed with a real-time MRI/US fusion platform with sensor-based registration. Clinically significant PCa was defined as Gleason score (GS) ≥ 7 or GS 6 with maximal cancer core length ≥ 4 mm for TB and according to Epstein criteria for RB. RESULTS: The overall CDR was 56 % (227/408). The CDR for primary biopsy was 74 % (60/81) and 57 % (67/117), 49 % (62/126), 45 % (38/84) for patients with 1, 2 and ≥ 3 prior negative biopsies. CDRs correlated with PI-RADS 2/3/4/5 were 16 % (5/32), 26 % (29/113), 62 % (94/152) and 89 % (99/111), respectively. The rates of significant tumors in relation to PI-RADS 2/3/4/5 were 60 % (3/5), 66 % (19/29), 74 % (70/94), 95 % (94/99). In 139 (61 %) cases with radical prostatectomy (RP), the rates of ≥ pT3 tumors in correlation with PI-RADS 4 and 5 were 20 % (11/56) and 49 % (32/65). PI-RADS constituted the strongest predictor of significant PCa detection (p < 0.007). CONCLUSIONS: Real-time MRI/US fusion-guided TB combined with RB improved PCa detection in patients with primary and repeat biopsies. The CDR was strongly correlated with a rising PI-RADS score, values of 4 and 5 increasing the detection of clinically significant tumors and leading to a higher histological stage after RP.

Flupyradifurone (Sivanto™) and its novel butenolide pharmacophore: Structural considerations.

Flupyradifurone (4-[(2,2-difluoroethyl)amino]-2(5H)-furanone), a member of the new class of butenolide insecticides, contains a novel bioactive scaffold as pharmacophore. It is very versatile in terms of application methods to a variety of crops, exhibits excellent and fast action against a broad spectrum of sucking pest insects including selected neonicotinoid resistant pest populations such as whiteflies and aphids expressing metabolic resistance mechanisms. As a partial agonist flupyradifurone reversibly binds to insect nicotinic acetylcholine receptors (nAChRs) and lacks metabolization by CYP6CM1, a cytochrome P450 over-expressed in cotton whiteflies resistant to imidacloprid and pymetrozine. The butenolide insecticides exhibit structure-activity relationships (SAR) that are different from other nAChR agonists such as the classes of neonicotinoids and sulfoximines. The paper briefly reviews the discovery of the butenolide insecticide flupyradifurone, its SAR differentiating it from established nAChR agonists and a molecular docking approach using the binding site model of CYP6CM1vQ of Bemisia tabaci known to confer metabolic resistance to neonicotinoid insecticides.

Critical role of spatial interaction between CD8⁺ and Foxp3⁺ cells in human gastric cancer: the distance matters.

PURPOSE: In various cancer types, an abundance of FoxP3(+) regulatory T cells (Treg) has been associated with an unfavorable outcome. Yet, the role of Treg on cancer immunity has been shown to be complex. In single cell marker technique, other tumor-infiltrating lymphocytes (TILs) such as cytotoxic CD8(+) T cells (CTL) also influenced prognosis. This study for the first time investigates the concurrent spatial distribution pattern of CD8(+) and FoxP3(+) TILs and their prognostic impact in human gastric cancer. MATERIALS AND METHODS: Tumor tissue microarrays of 50 patients with surgically treated adenocarcinoma of the cardia were studied. An immunohistochemical double staining of CD8(+) and FoxP3(+) TILs was performed. Cell counts and cell-to-cell distances in tumor epithelium and stroma were evaluated with image-processing software. Metastasis-free survival, no-evidence-of-disease survival, and overall survival were investigated (mean follow-up time 6.9 years). RESULTS: High intraepithelial infiltration of CD8(+) and FoxP3(+) TIL was associated with the improved 10-year metastasis-free survival (83 vs. 54%, p = 0.04 and 85 vs. 59%, p = 0.09, respectively). Considering cell-to-cell distance and comparing patients with functional (30-110 µm) versus nonfunctional distances of CD8(+) and FoxP3(+) TILs, 10-year survival rates differed between 89 and 55% (p = 0.009), respectively. CONCLUSION: Prognostic influence of tumor-infiltrating immune cells in gastric cancer critically depends on their cell-to-cell distance. FoxP3(+) TILs must be located within a distance between 30 and 110 µm of CD8(+) T cells to positively impact on prognosis.