ST6GAL1-mediated aberrant sialylation promotes prostate cancer progression.

Aberrant glycosylation is a universal feature of cancer cells, and cancer-associated glycans have been detected in virtually every cancer type. A common change in tumour cell glycosylation is an increase in α2,6 sialylation of N-glycans, a modification driven by the sialyltransferase ST6GAL1. ST6GAL1 is overexpressed in numerous cancer types, and sialylated glycans are fundamental for tumour growth, metastasis, immune evasion, and drug resistance, but the role of ST6GAL1 in prostate cancer is poorly understood. Here, we analyse matched cancer and normal tissue samples from 200 patients and verify that ST6GAL1 is upregulated in prostate cancer tissue. Using MALDI imaging mass spectrometry (MALDI-IMS), we identify larger branched α2,6 sialylated N-glycans that show specificity to prostate tumour tissue. We also monitored ST6GAL1 in plasma samples from >400 patients and reveal ST6GAL1 levels are significantly increased in the blood of men with prostate cancer. Using both in vitro and in vivo studies, we demonstrate that ST6GAL1 promotes prostate tumour growth and invasion. Our findings show ST6GAL1 introduces α2,6 sialylated N-glycans on prostate cancer cells and raise the possibility that prostate cancer cells can secrete active ST6GAL1 enzyme capable of remodelling glycans on the surface of other cells. Furthermore, we find α2,6 sialylated N-glycans expressed by prostate cancer cells can be targeted using the sialyltransferase inhibitor P-3FAX -Neu5Ac. Our study identifies an important role for ST6GAL1 and α2,6 sialylated N-glycans in prostate cancer progression and highlights the opportunity to inhibit abnormal sialylation for the development of new prostate cancer therapeutics. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Avoiding Unnecessary Biopsy after Multiparametric Prostate MRI with VERDICT Analysis: The INNOVATE Study.

Background In men suspected of having prostate cancer (PCa), up to 50% of men with positive multiparametric MRI (mpMRI) findings (Prostate Imaging Reporting and Data System [PI-RADS] or Likert score of 3 or higher) have no clinically significant (Gleason score ≤3+3, benign) biopsy findings. Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumor (VERDICT) MRI analysis could improve the stratification of positive mpMRI findings. Purpose To evaluate VERDICT MRI, mpMRI-derived apparent diffusion coefficient (ADC), and prostate-specific antigen density (PSAD) as determinants of clinically significant PCa (csPCa). Materials and Methods Between April 2016 and December 2019, men suspected of having PCa were prospectively recruited from two centers and underwent VERDICT MRI and mpMRI at one center before undergoing targeted biopsy. Biopsied lesion ADC, lesion-derived fractional intracellular volume (FIC), and PSAD were compared between men with csPCa and those without csPCa, using nonparametric tests subdivided by Likert scores. Area under the receiver operating characteristic curve (AUC) was calculated to test diagnostic performance. Results Among 303 biopsy-naive men, 165 study participants (mean age, 65 years ± 7 [SD]) underwent targeted biopsy; of these, 73 had csPCa. Median lesion FIC was higher in men with csPCa (FIC, 0.53) than in those without csPCa (FIC, 0.18) for Likert 3 (P = .002) and Likert 4 (0.60 vs 0.28, P < .001) lesions. Median lesion ADC was lower for Likert 4 lesions with csPCa (0.86 × 10-3 mm2/sec) compared with lesions without csPCa (1.12 × 10-3 mm2/sec, P = .03), but there was no evidence of a difference for Likert 3 lesions (0.97 × 10-3 mm2/sec vs 1.20 × 10-3 mm2/sec, P = .09). PSAD also showed no difference for Likert 3 (0.17 ng/mL2 vs 0.12 ng/mL2, P = .07) or Likert 4 (0.14 ng/mL2 vs 0.12 ng/mL2, P = .47) lesions. The diagnostic performance of FIC (AUC, 0.96; 95% CI: 0.93, 1.00) was higher (P = .02) than that of ADC (AUC, 0.85; 95% CI: 0.79, 0.91) and PSAD (AUC, 0.74; 95% CI: 0.66, 0.82) for the presence of csPCa in biopsied lesions. Conclusion Lesion fractional intracellular volume enabled better classification of clinically significant prostate cancer than did apparent diffusion coefficient and prostate-specific antigen density. Clinical trial registration no. NCT02689271 © RSNA, 2022 Online supplemental material is available for this article.

Technical efficacy and local recurrence after stereotactic radiofrequency ablation of 2653 liver tumors: a 15-year single-center experience with evaluation of prognostic factors.

PURPOSE: To assess the technical outcome and local tumor control of multi-probe stereotactic radiofrequency ablation (SRFA) in a large series of patients. Furthermore, to determine factors accounting for adverse outcomes. MATERIAL AND METHODS: Between 2003 and 2018, 865 patients were treated by SRFA for 2653 primary and metastatic liver tumors with a median tumor size of 2.0 cm (0.5 - 19 cm). Primary technical efficacy (PTE) and local recurrence (LR) were evaluated, and possible predictors for adverse events analyzed using uni- and multi-variable binary logistic regression. RESULTS: Overall, 2553 of 2653 tumors were successfully ablated at initial SRFA resulting in a PTE rate of 96.2%. Predictors of lower PTE rates were age > 70 years, tumor size > 5 cm, number of probes, location close to liver capsule/organs and segment II. LR occurred in 220 of 2653 tumors (8.3%) with the following predictors: age, tumor type/size, conglomerates, segments I/IVa/IVb, number of probes and location close to major vessels/bile duct. Multivariable analysis revealed tumor size > 5 cm (odds ratio [OR] 3.153), age > 70 years (OR 1.559), and location in segment II (OR 1.772) as independent prognostic factors for PTE, whereas tumor location close to major vessels (OR 1.653) and in segment IVb (OR 2.656) were identified as independent prognostic factors of LR. CONCLUSIONS: Stereotactic RFA is an attractive option in the management of primary or metastatic liver tumors with good local tumor control, even in large tumors. The presented prognostic factors for adverse local oncological outcome might help to stratify unfavorable tumors for ablation.

Characterization of Different Forms of Kava (Piper methysticum) Products by UPLC-MS/MS.

There are several forms of kava (Piper methysticum) products available for human consumption, and many factors are known to influence their chemical compositions and therefore their pharmacological properties. Because of the increased popularity of kava intake, a rigorous characterization of their content diversity is prerequisite, particularly due to its known potential to cause hepatotoxicity. To understand the composition diversity of kavalactones and flavokavains in commercial kava products, we developed a UPLC-MS/MS-based analytical method for the quantification of six kavalactones (kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin and desmethoxyyangonin) and two flavokavains (flavokavains A and B) and analyzed their contents in 28 different kava products in the form of capsules, tinctures, traditional aqueous suspensions and dried powders. Our results demonstrated a great variation in terms of the total and relative abundance of the analyzed kavalactones and flavokavains among the analyzed kava preparations. More importantly, the kavalactone abundance in the product label could differ up to 90% from our experimental measurements. Therefore, more rigorous and comprehensive quality control of kava products is required with respect to the content of individual kavalactones and flavokavains. Accurate content information is essential to understand the pharmacological properties and safety of different kava products.

Stereotactic radiofrequency ablation of tumors at the hepatic venous confluence.

BACKGROUND: Radiofrequency ablation (RFA) is subject to "heat-sink" effects, particularly for treatment of tumors adjacent to major vessels. METHODS: In this retrospective study, 104 patients with 137 tumors (40 HCC, 10 ICC and 54 metastatic liver tumors) close to (≤1 cm from) the hepatic venous confluence underwent stereotactic RFA (SRFA) between June 2003 and June 2018. Median tumor size was 3.7 cm (1.4-8.5) for HCC, 6.4 cm (0.5-11) for ICC and 3.8 cm (0.5-13) for metastases. Endpoints comprised safety, local tumor control, overall and disease-free survival. RESULTS: The overall major complication rate was 16.0% (20/125 ablations), where 8 (40%) were successfully treated by the interventional radiologist in the same anesthetic session and did not prolong hospital stay. 134/137 (97.8%) tumors were successfully ablated at initial SRFA. Local recurrence (LR) developed in 19/137 tumors (13.9%). The median and overall survival (OS) rates at 1-, 3-, and 5- years from the date of the first SRFA were 51.5 months, 73.5%, 67.0%, and 49.7% for HCC, 14.6 months, 60.0%, 32.0% and 32.0% for ICC and 38.1 months, 91.4%, 56.5% and 27.9% for metastatic disease, respectively. CONCLUSION: SRFA represents a viable alternative to hepatic resection for challenging tumors at the hepatic venous confluence.

Frequency and risk factors for major complications after stereotactic radiofrequency ablation of liver tumors in 1235 ablation sessions: a 15-year experience.

OBJECTIVES: To assess the frequency of major complications after multi-probe stereotactic radiofrequency ablation (SRFA) in a large cohort of patients over 15 years and to elucidate risk factors for adverse events. MATERIALS AND METHODS: A retrospective study was carried out between July 2003 and December 2018. Seven hundred ninety-three consecutive patients (median 65.0 years (0.3-88), 241 women and 552 men, were treated in 1235 SRFA sessions for 2475 primary and metastatic liver tumors with a median tumor size of 3.0 cm (0.5-18 cm). The frequency of major complications was evaluated according to SIR guidelines and putative predictors of adverse events analyzed using simple and multivariable logistic regression. RESULTS: Thirty-day mortality after SRFA was 0.5% (6/1235) with an overall major complication rate of 7.4% (91/1235). The major complication rate decreased from 11.5% (36/314) (before January 2011) to 6.0% (55/921) (p = 0.001). 50.5% (46/91) of major complications were successfully treated in the same anesthetic session by angiographic coiling for hemorrhage and chest tube insertion for pneumothorax. History of bile duct surgery/intervention, number of coaxial needles, and location of tumors in segment IVa or VIII were independent prognostic factors for major complications following multivariable logistic regression analysis. Simple logistic regression revealed the number of tumors, tumor size, location close to the diaphragm, tumor conglomerate, and segment VII as other significant predictors. CONCLUSION: SRFA of liver tumors is safe and can extend the treatment spectrum of conventional RFA. Adaptations over time combined with increasing experience resulted in a significant decrease in complications. KEY POINTS: • In 1235 ablation sessions in 793 patients over 15 years, we found a mortality rate of 0.5% (6/1235) and an overall major complication rate of 7.4%, which fell from 11.5 (36/314) to 6.0% (55/921, p = 0.001) after January 2011, likely due to procedural adaptations. • History of bile duct surgery/intervention (p = 0.013, OR = 3.290), number of coaxial needles (p = 0.026, OR = 1.052), and location of tumors in segment IVa (p = 0.016, OR = 1.989) or VIII (p = 0.038, OR = 1.635) were found to be independent prognostic factors. • Simple logistic regression revealed that number of tumors, tumor size, location close to the diaphragm, tumor conglomerates, and segment VII were other significant predictors of major complications.

Correction to: Machine learning classifiers can predict Gleason pattern 4 prostate cancer with greater accuracy than experienced radiologists.

The original version of this article, published on 11 June 2019, unfortunately contained a mistake. The following correction has therefore been made in the original: In section "Multiparametric MRI review," the readers mentioned in the first sentence were partly incorrect.

Thermal ablation of CT 'invisible' liver tumors using MRI fusion: a case control study.

Purpose: To evaluate whether 'invisible' liver tumors on CT can be treated by stereotactic radiofrequency ablation (SRFA) using fusion of pre-ablation MRI.Methods: In this retrospective case-control study, 60 patients (14 with Hepatocellular carcinoma (HCC) and 46 with metastatic liver tumors) with CT 'invisible' lesions underwent SRFA using MRI-fusion between June 2005 and June 2018 ('fusion group'). For comparison, 60 patients who underwent SRFA without image fusion were selected using nearest neighbor propensity score matching ('control group'). Endpoints consisted of local tumor control, safety, overall and disease-free survival.Results: Major complications occurred in 6/69 ablations (8.7%) in the fusion group and in 6/89 ablations (6.7%) in the control group (p = 0.434). Primary technical efficacy rate (i.e., successful initial ablation) was 96.6% (28/29) for HCC and 97.9% (166/170) for metastatic disease in the fusion group and 100% (33/33) and 93.3% (184/194) in the control group, respectively (p = 0.468 and 0.064). Local recurrence (LR) was observed in 1/29 (3.5%) HCCs and in 6/170 metastases (4.0%) in the fusion group and 1/33 (3.0%) and 21/196 (10.7%) in the control group, respectively. The LR rate of metastasis in the control group was significantly higher (p = 0.007), although differences in OS and DFS did not reach statistical significance.Conclusions: Image fusion using pre-procedural MRI allows for ablation of CT-'invisible' liver tumors that are otherwise untreatable. Moreover, local oncological control was higher in metastatic liver tumors versus matched controls which suggests it could be useful tool for all stereotactic radiofrequency ablation procedures.

PEOPLE: PatiEnt prOstate samPLes for rEsearch, a tissue collection pathway utilizing magnetic resonance imaging data to target tumor and benign tissue in fresh radical prostatectomy specimens.

BACKGROUND: Over 1 million men are diagnosed with prostate cancer each year worldwide, with a wide range of research programs requiring access to patient tissue samples for development of improved diagnoses and treatments. A random sampling of prostate tissue is sufficient for certain research studies; however, there is growing research need to target areas of the aggressive tumor as fresh tissue. Here we set out to develop a new pathway "PEOPLE: PatiEnt prOstate samPLes for rEsearch" to collect high-quality fresh tissue for research use, using magnetic resonance imaging (MRI) to target areas of tumor and benign tissue. METHODS: Prostate tissue was sampled following robotic radical prostatectomy, using MRI data to target areas of benign and tumor tissue. Initially, 25 cases were sampled using MRI information from clinical notes. A further 59 cases were sampled using an optimized method that included specific MRI measurements of tumor location along with additional exclusion criteria. All cases were reviewed in batches with detailed clinical and histopathological data recorded. For one subset of samples, DNA was extracted and underwent quality control. Ex vivo culture was carried out using the gelatin sponge method for an additional subset. RESULTS: Tumor was successfully fully or partially targeted in 64% of the initial cohort and 70% of the optimized cohort. DNA of high quality and concentration was isolated from 39 tumor samples, and ex vivo culture was successfully carried out in three cases with tissue morphology, proliferation, and apoptosis remaining comparable before and after 72 hours culture. CONCLUSION: Here we report initial data from the PEOPLE pathway; using a method for targeting areas of tumor within prostate samples using MRI. This method operates alongside the standard clinical pathway and minimizes additional input from surgical, radiological, and pathological teams, while preserving surgical margins and diagnostic tissue.

VERDICT MRI for Prostate Cancer: Intracellular Volume Fraction versus Apparent Diffusion Coefficient.

Background Biologic specificity of diffusion MRI in relation to prostate cancer aggressiveness may improve by examining separate components of the diffusion MRI signal. The Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumors (VERDICT) model estimates three distinct signal components and associates them to (a) intracellular water, (b) water in the extracellular extravascular space, and (c) water in the microvasculature. Purpose To evaluate the repeatability, image quality, and diagnostic utility of intracellular volume fraction (FIC) maps obtained with VERDICT prostate MRI and to compare those maps with apparent diffusion coefficient (ADC) maps for Gleason grade differentiation. Materials and Methods Seventy men (median age, 62.2 years; range, 49.5-82.0 years) suspected of having prostate cancer or undergoing active surveillance were recruited to a prospective study between April 2016 and October 2017. All men underwent multiparametric prostate and VERDICT MRI. Forty-two of the 70 men (median age, 67.7 years; range, 50.0-82.0 years) underwent two VERDICT MRI acquisitions to assess repeatability of FIC measurements obtained with VERDICT MRI. Repeatability was measured with use of intraclass correlation coefficients (ICCs). The image quality of FIC and ADC maps was independently evaluated by two board-certified radiologists. Forty-two men (median age, 64.8 years; range, 49.5-79.6 years) underwent targeted biopsy, which enabled comparison of FIC and ADC metrics in the differentiation between Gleason grades. Results VERDICT MRI FIC demonstrated ICCs of 0.87-0.95. There was no significant difference between image quality of ADC and FIC maps (score, 3.1 vs 3.3, respectively; P = .90). FIC was higher in lesions with a Gleason grade of at least 3+4 compared with benign and/or Gleason grade 3+3 lesions (mean, 0.49 ± 0.17 vs 0.31 ± 0.12, respectively; P = .002). The difference in ADC between these groups did not reach statistical significance (mean, 1.42 vs 1.16 × 10-3 mm2/sec; P = .26). Conclusion Fractional intracellular volume demonstrates high repeatability and image quality and enables better differentiation of a Gleason 4 component cancer from benign and/or Gleason 3+3 histology than apparent diffusion coefficient. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Sigmund and Rosenkrantz in this issue.

VERDICT-AMICO: Ultrafast fitting algorithm for non-invasive prostate microstructure characterization.

VERDICT (vascular, extracellular and restricted diffusion for cytometry in tumours) estimates and maps microstructural features of cancerous tissue non-invasively using diffusion MRI. The main purpose of this study is to address the high computational time of microstructural model fitting for prostate diagnosis, while retaining utility in terms of tumour conspicuity and repeatability. In this work, we adapt the accelerated microstructure imaging via convex optimization (AMICO) framework to linearize the estimation of VERDICT parameters for the prostate gland. We compare the original non-linear fitting of VERDICT with the linear fitting, quantifying accuracy with synthetic data, and computational time and reliability (performance and precision) in eight patients. We also assess the repeatability (scan-rescan) of the parameters. Comparison of the original VERDICT fitting versus VERDICT-AMICO showed that the linearized fitting (1) is more accurate in simulation for a signal-to-noise ratio of 20 dB; (2) reduces the processing time by three orders of magnitude, from 6.55 seconds/voxel to 1.78 milliseconds/voxel; (3) estimates parameters more precisely; (4) produces similar parametric maps and (5) produces similar estimated parameters with a high Pearson correlation between implementations, r2  > 0.7. The VERDICT-AMICO estimates also show high levels of repeatability. Finally, we demonstrate that VERDICT-AMICO can estimate an extra diffusivity parameter without losing tumour conspicuity and retains the fitting advantages. VERDICT-AMICO provides microstructural maps for prostate cancer characterization in seconds.

VERDICT MRI validation in fresh and fixed prostate specimens using patient-specific moulds for histological and MR alignment.

The VERDICT framework for modelling diffusion MRI data aims to relate parameters from a biophysical model to histological features used for tumour grading in prostate cancer. Validation of the VERDICT model is necessary for clinical use. This study compared VERDICT parameters obtained ex vivo with histology in five specimens from radical prostatectomy. A patient-specific 3D-printed mould was used to investigate the effects of fixation on VERDICT parameters and to aid registration to histology. A rich diffusion data set was acquired in each ex vivo prostate before and after fixation. At both time points, data were best described by a two-compartment model: the model assumes that an anisotropic tensor compartment represents the extracellular space and a restricted sphere compartment models the intracellular space. The effect of fixation on model parameters associated with tissue microstructure was small. The patient-specific mould minimized tissue deformations and co-localized slices, so that rigid registration of MRI to histology images allowed region-based comparison with histology. The VERDICT estimate of the intracellular volume fraction corresponded to histological indicators of cellular fraction, including high values in tumour regions. The average sphere radius from VERDICT, representing the average cell size, was relatively uniform across samples. The primary diffusion direction from the extracellular compartment of the VERDICT model aligned with collagen fibre patterns in the stroma obtained by structure tensor analysis. This confirmed the biophysical relationship between ex vivo VERDICT parameters and tissue microstructure from histology.

Simplified Luminal Water Imaging for the Detection of Prostate Cancer From Multiecho T2 MR Images.

BACKGROUND: Luminal water imaging (LWI) suffers less from imaging artifacts than the diffusion-weighted imaging used in multiparametric MRI of the prostate. LWI obtains multicompartment tissue information from a multiecho T2 dataset. PURPOSE: To compare a simplified LWI technique with apparent diffusion coefficient (ADC) in classifying lesions based on groupings of PI-RADS v2 scores. Secondary aims were to investigate whether LWI differentiates between histologically confirmed tumor and normal tissue as effectively as ADC, and whether LWI is correlated with the multicompartment parameters of the vascular, extracellular, and restricted diffusion for cytometry in tumors (VERDICT) diffusion model. STUDY TYPE: A subset of a larger prospective study. POPULATION: In all, 65 male patients aged 49-79 were scanned. FIELD STRENGTH/SEQUENCE: A 32-echo T2 and a six b-value diffusion sequence (0, 90, 500, 1500, 2000, 3000 s/mm2 ) at 3T. ASSESSMENT: Regions of interest were placed by a board-certified radiologist in areas of lesion and benign tissue and given PI-RADS v2 scores. STATISTICAL TESTS: Receiver operating characteristic and logistic regression analyses were performed. RESULTS: LWI classifies tissue as PI-RADS 1,2 or PI-RADS 3,4,5 with an area under curve (AUC) value of 0.779, compared with 0.764 for ADC. LWI differentiated histologically confirmed malignant from nonmalignant tissue with AUC, sensitivity, and specificity values of 0.81, 75%, and 87%, compared with 0.75, 83%, and 67% for ADC. The microstructural basis of the LWI technique is further suggested by the correspondence with the VERDICT diffusion-based microstructural imaging technique, with α, A1 , A2 , and LWF showing significant correlations. DATA CONCLUSION: LWI alone can predict PI-RADS v2 score groupings and detect histologically confirmed tumors with an ability similar to ADC alone without the limitations of diffusion-weighted MRI. This is important, given that ADC has an advantage in these tests as it already informs PI-RADS v2 scoring. LWI also provides multicompartment information that has an explicit biophysical interpretation, unlike ADC. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:910-917.

Multiparametric whole-body 3.0-T MRI in newly diagnosed intermediate- and high-risk prostate cancer: diagnostic accuracy and interobserver agreement for nodal and metastatic staging.

OBJECTIVES: To determine the diagnostic accuracy and interobserver concordance of whole-body (WB)-MRI, vs. 99mTc bone scintigraphy (BS) and 18fluoro-ethyl-choline (18F-choline) PET/CT for the primary staging of intermediate/high-risk prostate cancer. METHODS: An institutional review board approved prospective cohort study carried out between July 2012 and November 2015, whereby 56 men prospectively underwent 3.0-T multiparametric (mp)-WB-MRI in addition to BS (all patients) ± 18F-choline PET/CT (33 patients). MRI comprised pre- and post-contrast modified Dixon (mDixon), T2-weighted (T2W) imaging, and diffusion-weighted imaging (DWI). Patients underwent follow-up mp-WB-MRI at 1 year to derive the reference standard. WB-MRIs were reviewed by two radiologists applying a 6-point scale and a locked sequential read (LSR) paradigm for the suspicion of nodal (N) and metastatic disease (M1a and M1b). RESULTS: The mean sensitivity/specificity of WB-MRI for N1 disease was 1.00/0.96 respectively, compared with 1.00/0.82 for 18F-choline PET/CT. The mean sensitivity and specificity of WB-MRI, 18F-choline PET/CT, and BS were 0.90/0.88, 0.80/0.92, and 0.60/1.00 for M1b disease. ROC-AUC did not show statistically significant improvement for each component of the LSR; mean ROC-AUC 0.92, 0.94, and 0.93 (p < 0.05) for mDixon + DWI, + T2WI, and + contrast respectively. WB-MRI had an interobserver concordance (κ) of 0.79, 0.68, and 0.58 for N1, M1a, and M1b diseases respectively. CONCLUSIONS: WB-MRI provides high levels of diagnostic accuracy for both nodal and metastatic bone disease, with higher levels of sensitivity than BS for metastatic disease, and similar performance to 18F-choline PET/CT. T2 and post-contrast mDixon had no significant additive value above a protocol comprising mDixon and DWI alone. KEY POINTS: • A whole-body MRI protocol comprising unenhanced mDixon and diffusion-weighted imaging provides high levels of diagnostic accuracy for the primary staging of intermediate- and high-risk prostate cancer. • The diagnostic accuracy of whole-body MRI is much higher than that of bone scintigraphy, as currently recommended for clinical use. • Staging using WB-MRI, rather than bone scintigraphy, could result in better patient stratification and treatment delivery than is currently provided to patients worldwide.

Multi-parametric MRI zone-specific diagnostic model performance compared with experienced radiologists for detection of prostate cancer.

OBJECTIVES: Compare the performance of zone-specific multi-parametric-MRI (mp-MRI) diagnostic models in prostate cancer detection with experienced radiologists. METHODS: A single-centre, IRB approved, prospective STARD compliant 3 T MRI test dataset of 203 patients was generated to test validity and generalisability of previously reported 1.5 T mp-MRI diagnostic models. All patients included within the test dataset underwent 3 T mp-MRI, comprising T2, diffusion-weighted and dynamic contrast-enhanced imaging followed by transperineal template ± targeted index lesion biopsy. Separate diagnostic models (transition zone (TZ) and peripheral zone (PZ)) were applied to respective zones. Sensitivity/specificity and the area under the receiver operating characteristic curve (ROC-AUC) were calculated for the two zone-specific models. Two radiologists (A and B) independently Likert scored test 3 T mp-MRI dataset, allowing ROC analysis for each radiologist for each prostate zone. RESULTS: Diagnostic models applied to the test dataset demonstrated a ROC-AUC = 0.74 (95% CI 0.67-0.81) in the PZ and 0.68 (95% CI 0.61-0.75) in the TZ. Radiologist A/B had a ROC-AUC = 0.78/0.74 in the PZ and 0.69/0.69 in the TZ. Radiologists A and B each scored 51 patients in the PZ and 41 and 45 patients respectively in the TZ as Likert 3. The PZ model demonstrated a ROC-AUC = 0.65/0.67 for the patients Likert scored as indeterminate by radiologist A/B respectively, whereas the TZ model demonstrated a ROC-AUC = 0.74/0.69. CONCLUSION: Zone-specific mp-MRI diagnostic models demonstrate generalisability between 1.5 and 3 T mp-MRI protocols and show similar classification performance to experienced radiologists for prostate cancer detection. Results also indicate the ability of diagnostic models to classify cases with an indeterminate radiologist score. KEY POINTS: • MRI diagnostic models had similar performance to experienced radiologists for classification of prostate cancer. • MRI diagnostic models may help radiologists classify tumour in patients with indeterminate Likert 3 scores.

Machine learning classifiers can predict Gleason pattern 4 prostate cancer with greater accuracy than experienced radiologists.

OBJECTIVE: The purpose of this study was: To test whether machine learning classifiers for transition zone (TZ) and peripheral zone (PZ) can correctly classify prostate tumors into those with/without a Gleason 4 component, and to compare the performance of the best performing classifiers against the opinion of three board-certified radiologists. METHODS: A retrospective analysis of prospectively acquired data was performed at a single center between 2012 and 2015. Inclusion criteria were (i) 3-T mp-MRI compliant with international guidelines, (ii) Likert ≥ 3/5 lesion, (iii) transperineal template ± targeted index lesion biopsy confirming cancer ≥ Gleason 3 + 3. Index lesions from 164 men were analyzed (119 PZ, 45 TZ). Quantitative MRI and clinical features were used and zone-specific machine learning classifiers were constructed. Models were validated using a fivefold cross-validation and a temporally separated patient cohort. Classifier performance was compared against the opinion of three board-certified radiologists. RESULTS: The best PZ classifier trained with prostate-specific antigen density, apparent diffusion coefficient (ADC), and maximum enhancement (ME) on DCE-MRI obtained a ROC area under the curve (AUC) of 0.83 following fivefold cross-validation. Diagnostic sensitivity at 50% threshold of specificity was higher for the best PZ model (0.93) when compared with the mean sensitivity of the three radiologists (0.72). The best TZ model used ADC and ME to obtain an AUC of 0.75 following fivefold cross-validation. This achieved higher diagnostic sensitivity at 50% threshold of specificity (0.88) than the mean sensitivity of the three radiologists (0.82). CONCLUSIONS: Machine learning classifiers predict Gleason pattern 4 in prostate tumors better than radiologists. KEY POINTS: • Predictive models developed from quantitative multiparametric magnetic resonance imaging regarding the characterization of prostate cancer grade should be zone-specific. • Classifiers trained differently for peripheral and transition zone can predict a Gleason 4 component with a higher performance than the subjective opinion of experienced radiologists. • Classifiers would be particularly useful in the context of active surveillance, whereby decisions regarding whether to biopsy are necessitated.

Stereotactic radiofrequency ablation of subcardiac hepatocellular carcinoma: a case-control study.

Purpose: The purpose of this study is to evaluate the safety and efficacy of stereotactic radiofrequency ablation (SRFA) for the treatment of subcardiac hepatocellular carcinoma (HCC). Material and methods: From 2003 to 2018, 79 consecutive patients underwent 104 multi-probe SRFA sessions for the treatment of 114 subcardiac HCC with a median size of 2.5 cm (0.5-9.5 cm). The results were compared with a randomly selected control group of 79 patients with 242 HCC with a median size of 2.0 cm (0.5-12 cm) following SRFA in other (non-subcardiac) locations with propensity score matching. Results: The 95.6% of the tumors were successfully treated by the first ablation session (primary technical efficacy rate) and 99.1% after the second session (secondary technical efficacy rate). Local tumor recurrence developed in 8 nodules (7.0%). Major complication and perioperative mortality rates were 7.7% (8/104) and 1% (1/104), respectively. The overall survival (OS) rates from the date of the first SRFA with single subcardiac HCCs were 92%, 77% and 65% at 1, 3 and 5 years, respectively, with a median OS of 90.6 months. The disease-free survival (DFS) after SRFA was 75, 34 and 34%, at 1, 3 and 5 years, respectively, with a median DFS of 19.1 months. There was no statistically significant difference with the control group in terms of local tumor control, safety, OS and DFS. Conclusion: SRFA of subcardiac tumors is as safe and efficacious as when treating tumors remote from the heart.

National implementation of multi-parametric magnetic resonance imaging for prostate cancer detection - recommendations from a UK consensus meeting.

OBJECTIVES: To identify areas of agreement and disagreement in the implementation of multi-parametric magnetic resonance imaging (mpMRI) of the prostate in the diagnostic pathway. MATERIALS AND METHODS: Fifteen UK experts in prostate mpMRI and/or prostate cancer management across the UK (involving nine NHS centres to provide for geographical spread) participated in a consensus meeting following the Research and Development Corporation and University of California-Los Angeles (UCLA-RAND) Appropriateness Method, and were moderated by an independent chair. The experts considered 354 items pertaining to who can request an mpMRI, prostate mpMRI protocol, reporting guidelines, training, quality assurance (QA) and patient management based on mpMRI levels of suspicion for cancer. Each item was rated for agreement on a 9-point scale. A panel median score of ≥7 constituted 'agreement' for an item; for an item to reach 'consensus', a panel majority scoring was required. RESULTS: Consensus was reached on 59% of items (208/354); these were used to provide recommendations for the implementation of prostate mpMRI in the UK. Key findings include prostate mpMRI requests should be made in consultation with the urological team; mpMRI scanners should undergo QA checks to guarantee consistently high diagnostic quality scans; scans should only be reported by trained and experienced radiologists to ensure that men with unsuspicious prostate mpMRI might consider avoiding an immediate biopsy. CONCLUSIONS: Our consensus statements demonstrate a set of criteria that are required for the practical dissemination of consistently high-quality prostate mpMRI as a diagnostic test before biopsy in men at risk.

Perivascular extension of microwave ablation zone: demonstrated using an ex vivo porcine perfusion liver model.

Microwave ablation (MWA) has been proposed to suffer less from the heat sink effect compared to radiofrequency ablation but has been reported to cause extension of the ablation zone along intrahepatic vessels in clinical practice. To study this effect in detail, eight fresh porcine livers were perfused in an ex vivo organ perfusion system. Livers were perfused with oxygenated, O-positive human blood at 37 °C. Perfusion was discontinued immediately before ablation in the non-perfused group (n = 4) whilst in the perfused group (n = 4) perfusion was maintained during MWA (140 W X 2 min). Large intrahepatic vessels (> 6 mm) were avoided using ultrasound. MWA zones were bisected within 30 min of perfusion termination and sections were fixed in formalin and stained with H&E and NADH to assess cell viability. Magnetic resonance imaging (MRI) was performed on two livers (one perfused, one non-perfused) to provide imaging correlation before sectioning. Twenty-one out of a total of 30 MW ablation zones (70%) showed extension of the ablation zone along a vessel. There was no statistically significant difference (p = 1) in the incidence of ablation zone extension between perfused (9/13, 69%) and non-perfused organs (12/17, 71%). MRI also demonstrated ablation zone extension along blood vessels correlating with macroscopy in two livers. NADH staining also confirmed extension of the ablation zone. Liver MWA appears to be commonly associated with propagated thermal injury along adjacent vessels and occurs independent of active blood flow. In order to avoid possible complications through non-target tissue injury, this effect requires further investigation.