Adrenal Mass Biopsy in Patients Without Extraadrenal Primary Malignancy: A Multicenter Study.

BACKGROUND. Adrenal washout CT is not useful for evaluating incidental adrenal masses in patients without known or suspected primary extraadrenal malignancy. OBJECTIVE. The purpose of our study was to evaluate the diagnostic utility of adrenal mass biopsy in patients without known or suspected extraadrenal primary malignancy. METHODS. This retrospective six-center study included 69 patients (mean age, 56 years; 32 men, 37 women) without known or suspected extraadrenal primary malignancy who underwent image-guided core needle biopsy between January 2004 and June 2021 of a mass suspected to be arising from the adrenal gland. Biopsy results were classified as diagnostic or nondiagnostic. For masses resected after biopsy, histopathologic concordance was assessed between diagnoses from biopsy and resection. Masses were classified as benign or malignant by resection or imaging follow-up, and all nondi-agnostic biopsies were classified as false results. RESULTS. The median mass size was 7.4 cm (range, 1.9-19.2 cm). Adrenal mass biopsy had a diagnostic yield of 64% (44/69; 95% CI, 51-75%). After biopsy, 25 masses were resected, and 44 had imaging follow-up. Of the masses that were resected after diagnostic biopsy, diagnosis was concordant between biopsy and resection in 100% (12/12). Of the 13 masses that were resected after nondiagnostic biopsy, the diagnosis from re-section was benign in eight masses and malignant in five masses. The 44 masses with imaging follow-up included one mass with diagnostic biopsy yielding benign adenoma and two masses with nondiagnostic biopsy results that were classified as malignant by imaging follow-up. Biopsy had overall sensitivity and specificity for malignancy of 73% (22/30) and 54% (21/39), respectively; diagnostic biopsies had sensitivity and specificity for malignancy of 96% (22/23) and 100% (21/21), respectively. Among nine nondi-agnostic biopsies reported as adrenocortical neoplasm, six were classified as malignant by the reference standard (resection showing adrenocortical carcinoma in four, resection showing adrenocortical neoplasm of uncertain malignant potential in one, imaging follow-up consistent with malignancy in one). CONCLUSION. Adrenal mass biopsy had low diagnostic yield, with low sensitivity and low specificity for malignancy. A biopsy result of adrenocortical neoplasm did not reliably differentiate benign and malignant adrenal masses. CLINICAL IMPACT. Biopsy appears to have limited utility for the evaluation of incidental adrenal masses in patients without primary extraadrenal malignancy.

Quantitative Prostate MRI.

Prostate MRI is reported in clinical practice using the Prostate Imaging and Data Reporting System (PI-RADS). PI-RADS aims to standardize, as much as possible, the acquisition, interpretation, reporting, and ultimately the performance of prostate MRI. PI-RADS relies upon mainly subjective analysis of MR imaging findings, with very few incorporated quantitative features. The shortcomings of PI-RADS are mainly: low-to-moderate interobserver agreement and modest accuracy for detection of clinically significant tumors in the transition zone. The use of a more quantitative analysis of prostate MR imaging findings is therefore of interest. Quantitative MR imaging features including: tumor size and volume, tumor length of capsular contact, tumor apparent diffusion coefficient (ADC) metrics, tumor T1 and T2 relaxation times, tumor shape, and texture analyses have all shown value for improving characterization of observations detected on prostate MRI and for differentiating between tumors by their pathological grade and stage. Quantitative analysis may therefore improve diagnostic accuracy for detection of cancer and could be a noninvasive means to predict patient prognosis and guide management. Since quantitative analysis of prostate MRI is less dependent on an individual users' assessment, it could also improve interobserver agreement. Semi- and fully automated analysis of quantitative (radiomic) MRI features using artificial neural networks represent the next step in quantitative prostate MRI and are now being actively studied. Validation, through high-quality multicenter studies assessing diagnostic accuracy for clinically significant prostate cancer detection, in the domain of quantitative prostate MRI is needed. This article reviews advances in quantitative prostate MRI, highlighting the strengths and limitations of existing and emerging techniques, as well as discussing opportunities and challenges for evaluation of prostate MRI in clinical practice when using quantitative assessment. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

Prevalence of prostate cancer in PI-RADS version 2.1 T2-weighted transition zone 'nodule in nodule' and 'homogeneous mildly hypointense area between nodules' criteria: MRI-radical prostatectomy histopathological evaluation.

OBJECTIVES: To evaluate the prevalence of prostate cancer (PCa) of two PI-RADS version (v) 2.1 transition zone (TZ) features (PI-RADS 1 ['nodule in nodule'] and 2 ['homogeneous mildly hypointense area between nodules']). METHODS: With an institutional review board approval, from a 5-year cohort between 2012 and 2017, we retrospectively identified 53 consecutive men with radical prostatectomy (RP) confirmed TZ tumors and MRI. Three blinded radiologists (R1/2/3) independently evaluated T2-weighted and diffusion-weighted imaging (DWI) using PI-RADS v2.1 for the presence of (1) 'nodule in nodule' (recording 'cystic change', inner nodule encapsulation, size, and DWI score) and (2) 'homogeneous mildly hypointense area between nodules' (also recording size and DWI score). MRI-RP maps established ground truth. Primary tumor was evaluated assessing PI-RADS v2.1 category, size, and presence of imaging variants. RESULTS: R1/2/3 identified 26/18/22 'nodule in nodule' respectively with 7.7% (2/26; 95% confidence interval [95% CI]: 0.1-17.9%), 5.6% (1/18; 95% CI: 0.01-16.1%), and 4.5% (1/22; 95% CI: 0.01-13.3%) PCa (both Gleason score 3 + 4 = 7). Agreement was fair-to-substantial, kappa = 0.222-0.696. 'Cystic change', inner nodule absent/incomplete encapsulation and DWI score ≥ 4 for R1/R2/R2 were present in 80.8% (21/26), 46.2% (12/26), 7.7% (2/26); 94.4% (17/18), 33.3% (6/18), 5.6% (1/18); and 59.1% (13/22), 63.6% (14/22), 9.1% (2/22). Both PCa had inner nodule absent/incomplete encapsulation and DWI score ≥ 4. No other TZ tumors demonstrated 'nodule in nodule', nodule 'cystic change', or 'homogeneous mildly hypointense area between nodules'. R1/2/3 identified 5/6/13 'homogeneous mildly hypointense area between nodules' with zero PCa for any reader (upper bound 95% CI: 24.7-52.2%). Interobserver agreement was fair-to-substantial, kappa = 0.104-0.779. CONCLUSION: The proportion of cancers in PI-RADS v2.1 'nodule in nodule' was low (~5-8%) with zero cancers detected in 'homogeneous mildly hypointense area between nodules'. When 'nodule in nodule' inner nodule shows absent or incomplete encapsulation with marked restricted diffusion, PCa may be considered; however, this warrants further studies. KEY POINTS: • The prevalence of clinically significant prostate cancers in PI-RADS v2.1 'nodule in nodule' was low (5-8%, 95% CI: 0.1-17.9%). • Clinically significant prostate cancer was only detected in the 'nodule in nodule' variant when the inner nodule showed absent or incomplete encapsulation ('atypical nodule') with marked restricted diffusion. • 'Homogeneous mildly hypointense area between nodules' is likely benign with no cancers identified in the current study, however, with a wide 95% CI due to low prevalence.

Prevalence of Prostate Cancer in PI-RADS Version 2.1 Transition Zone Atypical Nodules Upgraded by Abnormal DWI: Correlation With MRI-Directed TRUS-Guided Targeted Biopsy.

BACKGROUND. In PI-RADS version 2.1 (v2.1), atypical transition zone (TZ) nodules (homogeneous circumscribed nodules without full encapsulation) assigned category 2 can be upgraded to category 3 when showing markedly restricted diffusion. The prevalence of prostate cancer (PCa) in DWI-upgraded atypical nodules is unknown. OBJECTIVE. The purpose of this study was to evaluate the prevalence of PCa in DWI-upgraded TZ atypical nodules and compare PCa diagnosis rate with that for conventional score 3 TZ nodules. METHODS. We retrospectively identified 104 consecutive cases of men who underwent MRI-directed transrectal ultrasound-guided targeted biopsy of 109 TZ category 3 or lower nodules performed between January 2015 and July 2018. Three radiologists who were blinded to the scores independently rescored lesions using PI-RADS v2.1. Agreement was assessed by Cohen kappa score. Consensus diagnosis was established by a second-round joint review. The number of TZ atypical nodules with or without DWI-upgraded and conventional score 3 TZ nodules were recorded and compared with targeted biopsy results including any PCa or clinically significant PCa (csPCa, defined as International Society of Urological Pathology [ISUP] grade group ≥ 2) using chi-square analysis. RESULTS. There were 95 PI-RADS v2.1 category 3 (55 conventional T2-weighted MRI score 3 and 40 DWI-upgraded atypical nodules) and 14 category 2 or 1 nodules at consensus review with patient mean age of 64.8 ± 8.4 (SD) years, PSA of 10.6 ± 7.2 ng/mL, and nodule size of 15.1 ± 5.5 mm. Interobserver agreement ranged from slight to substantial for radiologists 1 and 2 (κ = 0.329), radiologists 1 and 3 (κ = 0.548), and radiologists 2 and 3 (κ = 0.652). From the 40 upgraded atypical nodules, 27.5% (11/40) had PCa and 7.5% (3/40) had csPCa (8 ISUP grade 1, 2 ISUP grade 2, 1 ISUP grade 3), compared with 43.6% (24/55) PCa and 20.0% (11/55) csPCa (13 ISUP grade 1, 6 ISUP grade 2, 3 ISUP grade 3, 2 ISUP grade 4) diagnosed in conventional T2-weighted score 3 nodules (p = .09 for csPCA and p = .11 for PCa). PCa was not diagnosed in any atypical nodule that was not upgraded on DWI. CONCLUSION. The prevalence of PCa in DWI-upgraded TZ atypical nodules was low (≈ 28% for any PCa and ≈ 8% for csPCa) and compared favorably to csPCa diagnosis rates in conventional TZ score 3 nodules. CLINICAL IMPACT. This study validates the DWI upgrade rule introduced in PI-RADS v2.1 for atypical nodules, which showed significant prostate cancer detection rates at targeted biopsy similar to those of conventional T2-weighted MRI TZ score 3 nodules.

Accuracy of the Liver Imaging Reporting and Data System in Computed Tomography and Magnetic Resonance Image Analysis of Hepatocellular Carcinoma or Overall Malignancy-A Systematic Review.

BACKGROUND & AIMS: The Liver Imaging Reporting and Data System (LI-RADS) categorizes observations from imaging analyses of high-risk patients based on the level of suspicion for hepatocellular carcinoma (HCC) and overall malignancy. The categories range from definitely benign (LR-1) to definitely HCC (LR-5), malignancy (LR-M), or tumor in vein (LR-TIV) based on findings from computed tomography or magnetic resonance imaging. However, the actual percentage of HCC and overall malignancy within each LI-RADS category is not known. We performed a systematic review to determine the percentage of observations in each LI-RADS category for computed tomography and magnetic resonance imaging that are HCCs or malignancies. METHODS: We searched the MEDLINE, Embase, Cochrane CENTRAL, and Scopus databases from 2014 through 2018 for studies that reported the percentage of observations in each LI-RADS v2014 and v2017 category that were confirmed as HCCs or other malignancies based on pathology, follow-up imaging analyses, or response to treatment (reference standard). Data were assessed on a per-observation basis. Random-effects models were used to determine the pooled percentages of HCC and overall malignancy for each LI-RADS category. Differences between categories were compared by analysis of variance of logit-transformed percentage of HCC and overall malignancy. Risk of bias and concerns about applicability were assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 tool. RESULTS: Of 454 studies identified, 17 (all retrospective studies) were included in the final analysis, consisting of 2760 patients, 3556 observations, and 2482 HCCs. The pooled percentages of observations confirmed as HCC and overall malignancy, respectively, were 94% (95% confidence interval [CI] 92%-96%) and 97% (95% CI 95%-99%) for LR-5, 74% (95% CI 67%-80%) and 80% (95% CI 75%-85%) for LR-4, 38% (95% CI 31%-45%) and 40% (95% CI 31%-50%) for LR-3, 13% (95% CI 8%-22%) and 14% (95% CI 9%-21%) for LR-2, 79% (95% CI 63%-89%) and 92% (95% CI 77%-98%) for LR-TIV, and 36% (95% CI 26%-48%) and 93% (95% CI 87%-97%) for LR-M. No malignancies were found in the LR-1 group. The percentage of HCCs and overall malignancies confirmed differed significantly among LR groups 2-5 (P < .00001). Patient selection was the most frequent factor that affected bias risk, because of verification bias and case-control study design. CONCLUSIONS: In a systematic review, we found that increasing LI-RADS categories contained increasing percentages of HCCs and overall malignancy based on reference standard confirmation. Of observations categorized as LR-M, 93% were malignancies and 36% were confirmed as HCCs. The percentage of HCCs found in the LR-2 and LR-3 categories indicate the need for a more active management strategy than currently recommended. Prospective studies are needed to validate these findings. PROSPERO number CRD42018087441.

Update on Indications for Percutaneous Renal Mass Biopsy in the Era of Advanced CT and MRI.

OBJECTIVE. The objective of this article is to review the burgeoning role of percutaneous renal mass biopsy (RMB). CONCLUSION. Percutaneous RMB is safe, accurate, and indicated for an expanded list of clinical scenarios. The chief scenarios among them are to prevent treatment of benign masses and help select patients for active surveillance (AS). Imaging characterization of renal masses has improved; however, management decisions often depend on a histologic diagnosis and an assessment of biologic behavior of renal cancers, both of which are currently best achieved with RMB.

Use of Quantitative T2-Weighted and Apparent Diffusion Coefficient Texture Features of Bladder Cancer and Extravesical Fat for Local Tumor Staging After Transurethral Resection.

OBJECTIVE. The purpose of this study was to determine whether quantitative T2-weighted imaging and apparent diffusion coefficient (ADC) texture features of bladder cancer and extravesical fat are predictive of muscle invasive bladder cancer (category ≥ T2) and extravesical (category ≥ T3) disease after transurethral resection of a bladder tumor (TURBT). MATERIALS AND METHODS. In this retrospective study, 36 patients (27 men, nine women; mean age, 71 years) were identified who underwent post-TURBT MRI followed by cystectomy without intervening treatment from August 2011 through October 2016. Texture features of bladder cancer and extravesical fat adjacent to the tumor on T2-weighted and ADC images were extracted and compared between category ≤ T2 versus ≥ T3 and category T1 versus ≥ T2 tumors by means of Kruskal-Wallis or Mann-Whitney U test. Multivariate logistic regression analysis was performed, and ROC curves were calculated. RESULTS. Twenty-six of the 36 (72%) tumors were ≥ T2, and 53% (19/36) were ≥ T3. In multivariate analysis, bladder cancer entropy on T2-weighted images (p = 0.006; odds ratio [OR], 4.56; 95% CI, 1.49-20.41; AUC, 0.85) and ADC maps (p = 0.019; OR, 2.24; 95% CI, 1.13-5.31; AUC, 0.80) and extravesical fat entropy on T2-weighted images (p = 0.005; OR, 17.50; 95% CI, 3.01-200.80; AUC, 0.84) and ADC maps (p = 0.002; OR, 6.54; 95% CI, 1.90-32.40; AUC, 0.82) remained greater for ≥ T3 than for ≤ T2 tumors. In multivariate analysis, bladder cancer entropy on ADC maps (p = 0.027; OR, 2.11; 95% CI, 1.08-5.03; AUC, 0.76) and extravesical fat entropy on T2-weighted images (p = 0.010; OR, 5.33; 95% CI, 1.25-3.79; AUC, 0.78) and ADC maps (p = 0.029; OR, 3.80; 95% CI, 1.25-16.97; AUC, 0.74) remained greater for category ≥ T2 compared with category T1 tumors. CONCLUSION. Greater entropy of primary bladder cancers and extravesicular fat was observed in category ≥ T3 than in category ≤ T2 and in category ≥ T2 than in category T1 tumors. MRI texture analysis can help with local bladder cancer staging in patients who have undergone TURBT and may serve as a biomarker for higher local category bladder cancers.

Evaluation of MRI for diagnosis of extraprostatic extension in prostate cancer.

PURPOSE: To assess the ability of magnetic resonance imaging (MRI) to diagnose extraprostatic extension (EPE) in prostate cancer. MATERIALS AND METHODS: With Institutional Review Board (IRB) approval, 149 men with 170 ≥0.5 mL tumors underwent preoperative 3T MRI followed by radical prostatectomy (RP) between 2012-2015. Two blinded radiologists (R1/R2) assessed tumors using Prostate Imaging Reporting and Data System (PI-RADS) v2, subjectively evaluated for the presence of EPE, measured tumor size, and length of capsular contact (LCC). A third blinded radiologist, using MRI-RP-maps, measured whole-lesion: apparent diffusion coefficient (ADC) mean/centile and histogram features. Comparisons were performed using chi-square, logistic regression, and receiver operator characteristic (ROC) analysis. RESULTS: The subjective EPE assessment showed high specificity (SPEC = 75.4/91.3% [R1/R2]), low sensitivity (SENS = 43.3/43.6% [R1/R2]), and area-under (AU) ROC curve = 0.67 (confidence interval [CI] 0.61-0.73) R1 and 0.61 (CI 0.53-0.70) R2; (k = 0.33). PI-RADS v2 scores were strongly associated with EPE (P < 0.001 / P = 0.008; R1/R2) with AU-ROC curve = 0.72 (0.64-0.79) R1 and 0.61 (0.53-0.70) R2; (k = 0.44). Tumors with EPE were larger (18.8 ± 7.8 [median 17, range 6-51] vs. 18.8 ± 4.9 [12, 6-28] mm) and had greater LCC (21.1 ± 14.9 [16, 1-85] vs. 13.6 ± 6.1 [11.5, 4-30] mm); P < 0.001 and 0.002, respectively. AU-ROC for size was 0.73 (0.64-0.80) and LCC was 0.69 (0.60-0.76), respectively. Optimal SENS/SPEC for diagnosis of EPE were: size ≥15 mm = 67.7/66.7% and LCC ≥11 mm = 84.9/44.8%. 10th -centile ADC and ADC entropy were both associated with EPE (P = 0.02 and < 0.001), with AU-ROC = 0.56 (0.47-0.65) and 0.76 (0.69-0.83), respectively. Optimal SENS/SPEC for diagnosis of EPE with entropy ≥6.99 was 63.3/75.0%. 25th -centile ADC trended towards being significantly lower with EPE (P = 0.06) with no difference in other ADC metrics (P = 0.25-0.88). Size, LCC, and ADC entropy improved sensitivity but reduced specificity compared with subjective analysis with no difference in overall accuracy (P = 0.38). CONCLUSION: Measurements of tumor size, capsular contact, and ADC entropy improve sensitivity but reduce specificity for diagnosis of EPE compared to subjective assessment. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:176-185.

Prognostic value of Prostate Imaging and Data Reporting System (PI-RADS) v. 2 assessment categories 4 and 5 compared to histopathological outcomes after radical prostatectomy.

PURPOSE: To assess Prostate Imaging and Data Reporting System (PI-RADS) v. 2 score 4/5 lesions compared to Gleason score (GS) and stage after radical prostatectomy (RP) and to validate the proposed 15-mm size threshold that differentiates category 4 versus 5 lesions. MATERIALS AND METHODS: With Institutional Review Board (IRB) approval, 140 men underwent 3T magnetic resonance imaging (MRI) and RP between 2012-2015. Two blinded radiologists: 1) assigned PI-RADS v. 2 scores, 2) measured tumor size on axial T2 -weighted-MRI, and 3) assessed for extraprostatic extension (EPE). Interobserver agreement was calculated and consensus diagnoses achieved through reference standard (MRI-RP maps). PI-RADS v. 2 scores and tumor size were compared to GS and stage using chi-square, analysis of variance (ANOVA), and receiver operating characteristic (ROC) curve analysis. RESULTS: In all, 80.7% (113/140) of tumors were category 4 (n = 45) or 5 (n = 68) lesions (κ = 0.45). Overall tumor size was 18.2 ± 7.7 mm and category 5 lesions were larger (22.6 ± 6.8 versus 11.5 ± 1.9 mm, P < 0.001). High-risk (GS ≥8) tumors were larger than low- and intermediate-risk tumors (P = 0.016) and were more frequently, but not significantly so, category 5 lesions (78.9% [15/19] vs. 22.1% [4/10], P = 0.18). 67.3% (76/113) of patients had EPE. Category 5 lesions were strongly associated with EPE (P < 0.0001). Area under the ROC curve for diagnosis of EPE by size was 0.74 (confidence interval 0.64-0.83), with size ≥15 mm yielding a sensitivity/specificity of 72.4/64.9%. Size improved sensitivity for diagnosis of EPE compared to subjective assessment (sensitivity/specificity ranging from 46.1-48.7%/70.3-86.5%, κ = 0.29) (P = 0.028). CONCLUSION: PI-RADS v. 2 category 5 lesions are associated with higher Gleason scores and EPE. A 15-mm size threshold is reasonably accurate for diagnosis of EPE with increased sensitivity compared to subjective assessment. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:257-266.

MRI assessment of pathological stage and surgical margins in anterior prostate cancer (APC) using subjective and quantitative analysis.

PURPOSE: To evaluate magnetic resonance imaging (MRI) for assessment of extraprostatic extension (EPE) and positive surgical margins (PSM) in anterior prostate cancer (APC). MATERIALS AND METHODS: With Institutional Review Board approval, 25 APC (>2/3 of tumor anterior to urethra) were assessed using 3T MRI by two blinded radiologists for: size and maximal leading edge of tumor (relative to anterior fibromuscular stroma [AFMS]) on b ≥1000 sec/mm2 echo-planar-MRI fused onto T2 -weighted-MRI, invasion of AFMS and EPE. Comparisons were performed between APCs by EPE/PSM using chi-square, multivariable analysis, and receiver operator characteristic (ROC) analysis. RESULTS: The prevalence of EPE and PSM were 52% (13/25) and 36% (9/25). Tumor sizes were larger with EPE (22.5 ± 8.4 vs. 14.7 ± 6.3, P = 0.02) and PSM (23.0 ± 9.3 vs. 16.4 ± 7.0, P = 0.06). Area under ROC curve (AUC-ROC) for the diagnosis of EPE by tumor size was 0.77 (95% confidence interval [CI] 0.58-0.95); ≥16 mm size = sensitivity/specificity 69.2/66.7%. Maximal leading edge of tumor was greater with EPE (2.4 ± 2.2 vs. -0.2 ± 3.0) and PSM (2.8 ± 2.3 vs. -0.3 ± 2.5), (P = 0.023, 0.031). AUC-ROC for diagnosis of EPE/PSM by leading edge was 0.78 (CI 0.57-0.97) and 0.75 (CI 0.56-0.94). A ≥1 mm leading edge yielded sensitivity/specificity of 76.9/75.0% and 77.8/62.5% for diagnosis of EPE/PSM. 60-72% (15-18/25) tumors invaded AFMS (k = 0.74), which was not associated with EPE/PSM (P = 0.12-0.14). Radiologists' assessment of EPE had sensitivity/specificity of 61.5-69.2/50.0-75.0% (k = 0.53). CONCLUSION: Tumor size and leading edge of tumor relative to AFMS may enable diagnosis of EPE and positive surgical margins in APC. LEVEL OF EVIDENCE: 2 J. MAGN. RESON. IMAGING 2017;45:1296-1303.

Prostate Imaging Reporting and Data System, Version 2, Assessment Categories and Pathologic Outcomes in Patients With Gleason Score 3 + 4 = 7 Prostate Cancer Diagnosed at Biopsy.

OBJECTIVE: The purpose of this study is to assess associations between Prostate Imaging Reporting and Data System, version 2 (PI-RADSv2), categories and the presence of a tumor with a Gleason score (GS) of 4 + 3 = 7 or greater or the presence of extraprostatic extension (EPE) at radical prostatectomy (RP) in patients with a GS 3 + 4 = 7 tumor at biopsy. MATERIALS AND METHODS: A total of 81 men with GS 3 + 4 = 7 prostate cancer diagnosed by transrectal ultrasound-guided biopsy underwent multiparametric MRI and RP between 2012 and 2015. Two blinded radiologists assessed multiparametric MR images and assigned PI-RADSv2 assessment categories (categories 1-5) with the use of sector maps, which were compared with regard to the location of the tumor, the GS, and the presence of EPE at RP. Comparisons were performed between groups with the use of chi-square and multivariate analysis. Diagnostic accuracy was assessed using ROC curve analysis, and localization was compared using the Fisher exact test. RESULTS: A total of 53.1% of men (43/81) had EPE, and 21.0% (17/81) had GS 4 + 3 = 7 prostate cancer after RP, whereas 2.5% of men (2/81) had their tumors downgraded to GS 3 + 3 = 6. No statistically significant difference in patient age, prostate specific antigen level, or clinical stage existed between groups (p > 0.05). PI-RADSv2 assessment categories were significantly higher for GS 4 + 3 = 7 tumors (p = 0.03). PI-RADSv2 showed moderate accuracy for the diagnosis of GS 4 + 3 = 7 tumors (AUC, 0.65; 95% CI, 0.54-0.77), with a category of 4 or higher having a sensitivity and specificity for diagnosis of 94.1% and 23.4%, respectively. No patient with a PI-RADSv2 category lower than 3 had a GS 4 + 3 = 7 tumor. Accuracy of tumor localization ranged from 86.4% to 92.6%, with 88.2% of errors (15/17) occurring in GS 3 + 3 = 6 or GS 3 + 4 = 7 tumors (p = 0.30). PI-RADSv2 categories were noted to be higher when EPE was present (p < 0.001). Interobserver agreement was moderate (κ = 0.43). CONCLUSION: For GS 3 + 4 = 7 cancers detected at transrectal ultrasound-guided biopsy, higher PI-RADSv2 assessment categories are associated with upgrading to GS 4 + 3 = 7 cancer and with the presence of EPE after RP. A PI-RADSv2 score of 3 or higher was 100% sensitive for diagnosing GS 4 + 3 = 7 tumors.

Forgoing the Folate?-Contemporary Recommendations for Methanol Poisoning and Evidence Review.

Methanol poisonings can produce significant toxicity in humans, including acidosis, blindness, and death. The current mainstay of therapy is alcohol dehydrogenase (ADH) inhibition to prevent formation of formic acid and hemodialysis to correct acidosis and remove both parent compound and toxic metabolite. Folate has been recommended as an adjunctive therapy to increase formic acid oxidation into carbon dioxide and water. We retrospectively reviewed recommendation of folate therapy for methanol poisoning by our regional poison center from 2002 to 2012. One hundred two patients met inclusion criteria. Our findings demonstrate a sharp decline in folate recommendation over the course of the study period (48% vs. 12% during the years 2002-2006 and 2007-2012, respectively), despite similar rates of ADH inhibition, hemodialysis, and serious outcomes. This may be related to the approval of the use of fomepizole in methanol poisoning in 2002, which provides a quicker, more reliable means of ADH inhibition than ethanol infusions. We also provide a review of the available evidence of folate use in methanol poisoning.

Those Salicylate Cases-How Sweet Are They?

Owing to the complex metabolism of salicylates, both hyperglycemia and hypoglycemia have been reported with salicylate poisoning. The aim of this study was to characterize this relationship. Data from the Illinois Poison Center were retrospectively queried over a 5-year period (2008-2012), and patients with a salicylate concentration ≥30 mg/dL were included. Hypoglycemia and hyperglycemia were defined as glucose concentrations <55 and >140 mg/dL, respectively. Of the 160 patients included, most were normoglycemic (81%) and 19% were hyperglycemic. No patient experienced hypoglycemia. Our study indicates that hypoglycemia may be a very rare occurrence in the setting of salicylate poisoning. Clinicians must remain vigilant, regardless of the glucose concentration, when entertaining salicylism as an etiology in appropriate patients.

Targeting a cryptic allosteric site for selective inhibition of the oncogenic protein tyrosine phosphatase Shp2.

Protein tyrosine phosphatases (PTPs) have been the subject of considerable pharmaceutical-design efforts because of the ubiquitous connections between misregulation of PTP activity and human disease. PTP-inhibitor discovery has been hampered, however, by the difficulty in identifying cell-permeable compounds that can selectively target PTP active sites, and no PTP inhibitors have progressed to the clinic. The identification of allosteric sites on target PTPs therefore represents a potentially attractive solution to the druggability problem of PTPs. Here we report that the oncogenic PTP Shp2 contains an allosteric-inhibition site that renders the enzyme sensitive to potent and selective inhibition by cell-permeable biarsenical compounds. Because Shp2 contains no canonical tetracysteine biarsenical-binding motif, the enzyme's inhibitor-binding site is not readily predictable from its primary or three-dimensional structure. Intriguingly, however, Shp2's PTP domain does contain a cysteine residue (C333) at a position that is removed from the active site and is occupied by proline in other classical PTPs. We show that Shp2's unusual cysteine residue constitutes part of a Shp2-specific allosteric-inhibition site, and that Shp2's sensitivity to biarsenicals is dependent on the presence of the naturally occurring C333. The determinative role of this residue in conferring inhibitor sensitivity is surprising because C333's side chain is inaccessible to solvent in Shp2 crystal structures. The discovery of this cryptic Shp2 allosteric site may provide a means for targeting Shp2 activity with high specificity and suggests that buried-yet-targetable allosteric sites could be similarly uncovered in other protein families.

Magnetic resonance enterography in post-operative inflammatory bowel disease.

OBJECTIVE: To describe the role of magnetic resonance enterography (MRE) in patients with inflammatory bowel disease (IBD), and to review the expected post-operative appearance, as well as, potential surgical complications in this unique patient population. CONCLUSION: MRE compares favorably to CT Enterography (CTE) in terms of overall diagnostic accuracy and may provide better functional assessment of the small bowel through cine-MRI, diffusion-weighted imaging and dynamic contrast-enhancement. In the post-operative population, MRE provides critical information including: normal post-surgical anatomy, chronic strictures vs. active inflammation and disease/treatment-related complications. The post-operative IBD patient undergoes frequent repeated imaging and MRE may significantly reduce cumulative radiation dose while providing similar or improved diagnostic accuracy compared to CTE. MRE should be considered as an alternative imaging modality in this population.

Computed tomography for non-traumatic headache in the emergency department and the impact of follow-up testing on altering the initial diagnosis.

The purpose of this study was twofold: (1) to determine the incidence of positive computed tomography (CT) findings in patients presenting to the emergency department (ED) with non-traumatic headache at our institution and (2) to examine follow-up exams, including lumbar puncture, non-enhanced CT, CT angiogram, CT venogram, and magnetic resonance imaging (MRI), to see how often the use of further testing changes the diagnosis. With IRB approval, 865 patients were identified through ED requisitions for CT head with the indication of headache during the calendar year 2011. Exclusion criteria included head trauma, prior intracranial surgery, focal neurologic symptoms, and known intracranial mass. CT results were divided into three categories: P0, P1, and P2. Negative studies were graded as P0. Positive studies were subdivided into clinically insignificant or P1 and clinically significant or P2. Clinically significant was defined as requiring medical treatment. Subsequently, the electronic medical records and picture archiving and communication system (PACS) were reviewed to determine the incidence of follow-up exams, including lumbar puncture or imaging. The secondary tests were divided into the same P0, P1, and P2 categories. There were 254 positive studies: P1 clinically insignificant (27.1 %, 235/865) and P2 clinically significant (2.2 %, 19/865). Of 257 follow-up exams performed, the majority were lumbar punctures (36.0 %) or CT angiograms (29.5 %). In 19/257 exams or 7.4 %, the additional testing changed the clinically insignificant (P0/P1) diagnosis to a significant (P2) result. At our institution, there was a 2.2 % incidence of significant positive CT findings in patients presenting to the ED with non-traumatic headache. Follow-up testing was variable and resulted in a 7.4 % increase in the severity of diagnosis compared to the initial negative CT scan.

What proof is in your Christmas pudding? Is caring under the influence possible?

OBJECTIVES: To determine the ethanol concentration of commonly available Christmas puddings, and to extrapolate the blood alcohol content (BAC) of typical health care professionals after Christmas lunch at the hospital. DESIGN AND SETTING: We conducted fractional distillation of Christmas puddings and analysed the distillate for ethanol content. We then applied standard pharmacological and physiological assumptions to assess predicted BAC in typical male and female health care professionals at our hospital. MAIN OUTCOME MEASURES: Ethanol concentration of each pudding; estimated BAC of health care professionals after ingestion and at the end of a 30-minute lunch break. RESULTS: The concentration of ethanol in common Christmas puddings ranged from 0.260 to 1.685 g per 125 mg slice. The concentration of ethanol per pudding was not greater than the stipulated specifications on the packaging, where shown. After pudding ingestion, the theoretical BAC of a typical 70 kg male and 60 kg female health care professional ranged from 0.001 to 0.004 g/dL and from 0.001 to 0.006 g/dL, respectively. Neither male nor female staff had a predicted BAC > 0.000 g/dL by the end of the lunch break. CONCLUSION: Christmas puddings contain ethanol that does not all evaporate during the cooking process. However, the rise in BAC after ingestion of a typical slice of Christmas pudding was negligible and unlikely to affect work performance or safety or impair a health care worker's ability to make complex decisions.

Lipase-to-Amylase Ratio for the Prediction of Clinically Relevant Postoperative Pancreatic Fistula Following Pancreaticoduodenectomy.

OBJECTIVE: Postoperative pancreatic fistula (POPF) represents a leading cause of morbidity and mortality following major pancreatic resections. This study aimed to evaluate the use of postoperative drain fluid lipase-to-amylase ratio (LAR) for the prediction of clinically relevant fistulae (CR-POPF). METHODS: Consecutive patients undergoing pancreaticoduodenectomy between 2017 and 2021 at a tertiary centre were retrospectively reviewed. Univariable and multivariable analyses were performed to identify predictors for CR-POPF (ISGPS grade B/C). Receiver operating characteristic (ROC) curve analyses were conducted to evaluate the performance of LAR and determine optimum prediction thresholds. RESULTS: Among 130 patients, 28 (21.5%) developed CR-POPF. Variables positively associated with CR-POPF included soft gland texture, acinar cell density, diagnosis other than PDAC or chronic pancreatitis, resection without neoadjuvant therapy, and postoperative drain fluid lipase, amylase, and LAR (all P <0.05). Multivariable regression analysis identified LAR as an independent predictor of CR-POPF ( P <0.05). ROC curve analysis showed that LAR had moderate ability to predict CR-POPF on POD1 (AUC,0.64; 95%CI,0.54-0.74) and excellent ability on POD3 (AUC,0.85; 95%CI,0.78-0.92) and POD 5 (AUC,0.86; 95%CI,0.79-0.92). Optimum thresholds were consistent over PODs 1 to 5 (ratio>2.6) and associated with 92% sensitivity and 46% to 71% specificity. CONCLUSIONS: Postoperative drain fluid LAR represents a reliable predictor for the development of CR-POPF. With early prognostication, the postoperative care of patients at risk of developing high-grade fistulas may be optimized.