Associations and outcomes of prenatally detected rhombencephalosynapsis.

OBJECTIVE: To describe the association between prenatal imaging and neurodevelopmental outcomes of fetuses with rhombencephalosynapsis (RES). STUDY DESIGN: Thirty-four pregnancies complicated by RES were identified from our institutional databases based on US and/or MRI findings. Genetic testing results were gathered. In cases of termination of pregnancy, we studied the association between prenatal imaging and neuropathologic findings. For those who opted for expectant management, comprehensive developmental assessments and postnatal MRI imaging were evaluated. RESULTS: Over one third of fetuses in our cohort had complete RES. Common intracranial anomalies identified were mesencephalosynapsis, aqueduct stenosis and diencephalosynapsis. The degree of RES was not associated with the frequency of additional central nervous system anomalies. MRI had a good correlation with neuropathologic findings with regard to the degree of RES, aqueduct stenosis and mesencephalosynapsis. Postmortem autopsy showed that one third of our cases had VACTERL-H and almost all of those had complete RES. All liveborn neonates(n = 6) had aqueduct stenosis requiring ventriculoperitoneal shunting within days of delivery (median 5 days). While a large proportion of prenatally suspected complete RES were found to have partial RES on postnatal imaging, prenatal diagnosis of aqueduct stenosis remained unchanged. All children that were at least 2 years old (n = 3) had global developmental delay. CONCLUSION: Prenatal assessment of the RES severity is challenging and may be unreliable. Nevertheless, postnatal prognosis is poor for both complete and partial RES. Associated aqueductal stenosis, can be reliably assessed prenatally and this may contribute to worse postnatal prognosis than the degree of RES.

Revisiting the Implications of a Wide or Narrow Fetal Cavum Septi Pellucidi.

OBJECTIVES: To investigate short-term neonatal developmental outcomes in fetuses with an isolated wide or narrow cavum septi pellucidi (CSP) using new reference ranges. METHODS: A cross-sectional study on fetuses at 16 + 0 to 36 + 6 weeks of gestation between December 2020 and January 2022. CSP width reference ranges were constructed from low-risk pregnancies. Wide and narrow CSPs were defined as measurements above the 95th percentile and below the 5th percentile, respectively. For the primary outcome fetuses with normal neurosonograms were included. Neonatal developmental outcomes were assessed using the Survey of Well-being of Young Children (SWYC). RESULTS: A total of 352 fetuses were included in this study, of whom 138 were healthy and had uncomplicated neonatal outcomes. These fetuses constituted the control group and were used to construct the CSP width reference ranges. Of 185 fetuses in the neurosonography group, 9.7% had wide and 7.6% had narrow CSPs, of whom 33.3% and 22.2%, respectively, scored below the SWYC threshold for expected developmental milestones, a rate similar to that reported in the general population. CONCLUSIONS: The presence of a prenatally isolated wide or narrow CSP does not appear to increase the risk of neonatal neurodevelopmental delay.

Anterior extension of the choroid plexus into the frontal horns of the fetal lateral cerebral ventricles: Prenatal findings and postnatal outcome.

OBJECTIVE: To evaluate the short- and long-term outcome of fetuses with evidence of extension of the choroid plexus into the frontal horns. METHODS: This is a retrospective cohort study of fetuses diagnosed with isolated choroid plexi extending into the frontal horns. Fetuses with major central nervous system anomalies were excluded. Ultrasound and fetal/postnatal magnetic resonance imaging (MRI) were evaluated. Postnatal outcomes, including developmental assessment, were obtained. RESULTS: Twenty nine fetuses were diagnosed with choroid plexus extension (22 unilateral and 7 bilateral). Gestational age at diagnosis was 19.3 weeks. Three cases (10.3%) presented with nonspecific extra-CNS findings. At presentation, 8/29 (28%) cases had single/multiple choroid plexus cysts (CPC). Twenty-six (89.6%) cases underwent antenatal MRI. On MRI, four cases had punctate susceptibility weighted imaging (SWI) foci suggesting trace hemosiderin and two cases had ventriculomegaly. Antenatal follow-up demonstrated resolution of the choroid plexus extension in 90% (18/20). Gestational age at delivery was 39.6 weeks. All had normal neurologic examinations within 24 h of life. Postnatal MRI studies were notable for deep venous differences in seven cases. Long-term clinical outcome was assessed in 14 cases with a median follow-up of 1.75 years, with normal neurodevelopment reported in 13/14 (92.8%). CONCLUSIONS: Most fetuses with an anterior extension of the choroid plexus as the sole sonographic finding had favorable outcomes.

Prostate biopsy in the era of MRI-targeting: towards a judicious use of additional systematic biopsy.

OBJECTIVES: We aimed to develop and compare strategies that help optimize current prostate biopsy practice by identifying patients who may forgo concurrent systematic biopsy (SBx) in favor of MRI-targeted (TBx) alone. METHODS: Retrospective study on 745 patients who underwent combined MRI-TBx plus SBx. Primary outcome was the upgrade to clinically significant prostate cancer (csPCa; grade group ≥ 2) on SBx versus MRI-TBx. Variables (age, previous biopsy status, Prostate Imaging Reporting and Data System (PI-RADS) score, index lesion size/location, number of lesions, PSA, PSA density, prostate volume) associated with the primary outcome were identified by logistic regression and used for biopsy strategies. Clinical utility was assessed by decision curve analysis (DCA). RESULTS: SBx detected 47 (6%) additional men with csPCa. The risk of detecting csPCa uniquely on SBx was significantly lower in men with PI-RADS 5 (versus PI-RADS 3: OR 0.30, p = 0.03; versus PI-RADS 4: OR 0.33, p = 0.01), and previous negative biopsy (versus previous positive biopsy: OR 0.40, p = 0.007), and increased with age (per 10 years: OR 1.64, p = 0.016). No significant association was observed for other variables. DCA identified the following strategies as most useful: (a) avoid SBx in men with PI-RADS 5 and (b) additionally in those with previous negative biopsy, resulting in avoiding SBx in 201 (27%) and 429 (58%), while missing csPCa in 5 (1%) and 15 (2%) patients, respectively. CONCLUSION: Not all men benefit equally from the combination of SBx and MRI-TBx. SBx avoidance in men with PI-RADS 5 and/or previous negative biopsy may reduce the risk of excess biopsies with a low risk of missing csPCa. KEY POINTS: • In men undergoing MRI-targeted biopsy, the risk of detecting clinically significant prostate cancer (csPCa) only on additional systematic biopsy (SBx) decreased in men with PI-RADS 5, previous negative biopsy, and younger age. • Using these variables may help select men who could avoid the risk of excess SBx. • If missing csPCa in 5% was acceptable, forgoing SBx in men with PI-RADS 5 and/or previous negative biopsy enabled the highest net reduction in SBx.

Avoiding Unnecessary Biopsy: MRI-based Risk Models versus a PI-RADS and PSA Density Strategy for Clinically Significant Prostate Cancer.

Background In validation studies, risk models for clinically significant prostate cancer (csPCa; Gleason score ≥3+4) combining multiparametric MRI and clinical factors have demonstrated poor calibration (over- and underprediction) and limited use in avoiding unnecessary prostate biopsies. Purpose MRI-based risk models following local recalibration were compared with a strategy that combined Prostate Imaging Data and Reporting System (PI-RADS; version 2) and prostate-specific antigen density (PSAd) to assess the potential reduction of unnecessary prostate biopsies. Materials and Methods This retrospective study included 385 patients without prostate cancer diagnosis who underwent multipara-metric MRI (PI-RADS category ≥3) and MRI-targeted biopsy between 2015 and 2019. Recalibration and selection of the best-performing MRI model (MRI-European Randomized Study of Screening for Prostate Cancer [ERSPC], van Leeuwen, Radtke, and Mehralivand models) were undertaken in cohort C1 (n = 242; 2015-2017). The impact on biopsy decisions was compared with an alternative strategy (no biopsy for PI-RADS category 3 plus PSAd < 0.1 ng/mL per milliliter) in cohort C2 (n = 143; 2018-2019). Discrimination, calibration, and clinical utility were assessed by using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis, respectively. Results The prevalence of csPCa was 38% (93 of 242 patients) and 45% (64 of 143 patients) in cohorts C1 and C2, respectively. Decision curve analysis demonstrated the highest net benefit for the van Leeuwen and Mehralivand models in C1. Used for biopsy decisions in C2, van Leeuwen (AUC, 0.84; 95% CI: 0.77, 0.9) and Mehralivand (AUC, 0.79; 95% CI: 0.72, 0.86) enabled no net benefit at a risk threshold of 10%. Up to a risk threshold of 15%, net benefit remained inferior to the PI-RADS plus PSAd strategy, which avoided biopsy in 63 per 1000 men, without missing csPCa. Without prior recalibration in C1, three of four models (MRIERSPC, Radtke, Mehralivand) were poorly calibrated and not clinically useful in C2. Conclusion The number of unnecessary prostate biopsies in men with positive MRI may be safely reduced by using a prostate-specific antigen density-based strategy. In a risk-averse scenario, this strategy enabled better biopsy decisions compared with MRI-based risk models. ©RSNA, 2021 Online supplemental material is available for this article.

Does the Visibility of Grade Group 1 Prostate Cancer on Baseline Multiparametric Magnetic Resonance Imaging Impact Clinical Outcomes?

PURPOSE: We assessed whether the visibility of Grade Group (GG) 1 prostate cancer on baseline multiparametric magnetic resonance imaging affects clinical outcomes. MATERIALS AND METHODS: We evaluated 454 men who underwent multiparametric magnetic resonance imaging between 2006 and 2018 with maximum GG1 prostate cancer inclusive of magnetic resonance imaging targeted biopsy. Multiparametric magnetic resonance imaging was graded as negative, equivocal or positive. Assessed outcomes were treatment-free survival, biopsy upgrade-free survival and unfavorable disease at radical prostatectomy (pT 3 or greater and/or GG3 or greater). Kaplan-Meier and multivariable Cox proportional hazard analyses were used to estimate the impact of multiparametric magnetic resonance imaging and clinicopathological variables (age, year, prostate specific antigen density and measures of tumor volume on biopsy) on outcomes. RESULTS: During followup (median 45.2 months) 61 men had disease upgraded on followup biopsy and 139 underwent definitive treatment. In men with negative, equivocal and positive baseline multiparametric magnetic resonance imaging at 5 years, treatment-free survival was 79%, 73% and 49% (p <0.0001), treatment-free survival was 89%, 82% and 70% (p=0.002), and survival without unfavorable disease at radical prostatectomy was 98%, 98% and 86% (p=0.007), respectively. At multivariable analysis positive (HR 1.93, 95% CI 1.21-3.09, p=0.006) and equivocal multiparametric magnetic resonance imaging (HR 2.02, 95% CI 1.11-3.68, p=0.02) were associated with shorter treatment-free survival, and positive multiparametric magnetic resonance imaging was a significant prognostic factor for upgrade-free survival (HR 2.03, 95% CI 1.06-3.86, p=0.03) and unfavorable disease at radical prostatectomy (HR 4.45, 95% CI 1.39-18.17, p=0.01). CONCLUSIONS: Men with positive multiparametric magnetic resonance imaging and GG1 prostate cancer on magnetic resonance imaging targeted biopsy are at increased risk for intervention, upgrading and unfavorable disease at radical prostatectomy compared to those with multiparametric magnetic resonance imaging invisible GG1 prostate cancer.

Fetal myelomeningocele surgery: Only treating the tip of the iceberg.

OBJECTIVE: Fetal myelomeningocele (fMMC) surgery improves infant outcomes when compared with postnatal surgery. Surgical selection criteria and the option of pregnancy termination, however, limit the number of cases that are eligible for prenatal surgery. We aimed to quantify what proportion of cases could ultimately benefit from fetal therapy. METHODS: We retrospectively reviewed all cases of fMMC referred to a large tertiary care center over a 10-year period and assessed their eligibility for fetal surgery, pregnancy termination rates, and actual uptake of the surgery. RESULTS: Of 158 cases, 67 (42%) were ineligible for fetal surgery based on surgical exclusion criteria. Eleven fetuses (7%) had chromosomal anomalies, 10 of which (91%) had other anomalies on ultrasound. Thirty-four patients had a combination of maternal and fetal contraindications. Of the remaining 91 eligible cases (58%), 45 (49%) pregnancies were terminated, leaving only 46 (29% of initial 158 cases) as potential candidates for fetal repair. Actual uptake of fetal surgery was 15% (n = 14 of 91), but this increased after a national program was started. CONCLUSION: Only a minority of fMMC cases will ultimately undergo fetal surgery. These numbers support the centralization of care in expert centers.

Role of Magnetic Resonance Imaging Targeted Biopsy in Detection of Prostate Cancer Harboring Adverse Pathological Features of Intraductal Carcinoma and Invasive Cribriform Carcinoma.

PURPOSE: The aim of this study was to compare biopsy detection of intraductal and cribriform pattern invasive prostate carcinoma in multiparametric magnetic resonance imaging positive and negative regions of the prostate. MATERIALS AND METHODS: We queried a prospectively maintained, single institution database to identify patients who underwent multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy and concurrent systematic sextant biopsy of magnetic resonance imaging negative regions between January 2013 and May 2016. All multiparametric magnetic resonance imaging targets were reviewed retrospectively by 2 readers for the PI-RADS™ (Prostate Imaging-Reporting and Data System), version 2 score, the maximum dimension, the apparent diffusion coefficient parameter and whether positive or negative on dynamic contrast enhancement sequence. Biopsy slides were reviewed by 2 urological pathologists for Gleason score/Grade Group and the presence or absence of an intraductal/cribriform pattern. RESULTS: A total of 154 patients were included in study. Multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy and systematic sextant biopsy of magnetic resonance imaging negative regions were negative for prostate carcinoma in 51 patients, leaving 103 available for the correlation of multiparametric magnetic resonance imaging and the intraductal/cribriform pattern. Prostate carcinoma was identified by multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy in 93 cases and by systematic sextant biopsy of magnetic resonance imaging negative regions in 76 (p = 0.008). Intraductal/cribriform positive tumor was detected in 23 cases, including at the multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy site in 22 and at the systematic sextant biopsy of magnetic resonance imaging negative region site in 3 (p <0.001). The intraductal/cribriform pattern was significantly associated with a PI-RADS score of 5 and a decreasing apparent diffusion coefficient value (p = 0.008 and 0.005, respectively). In 19 of the 23 cases with the intraductal/cribriform pattern prior 12-core standard systematic biopsy was negative in 8 and showed Grade Group 1 disease in 11. CONCLUSIONS: Multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy was associated with significantly increased detection of intraductal/cribriform positive prostate carcinoma compared to systematic sextant biopsy of multiparametric magnetic resonance imaging negative regions. This supports the role of magnetic resonance imaging to enhance the detection of clinically aggressive intraductal/cribriform positive prostate carcinoma.

Evaluation of an Aggressive Prostate Biopsy Strategy in Men Younger than 50 Years.

PURPOSE: Longitudinal cohort studies and guidelines demonstrate that prostate specific antigen 1 ng/ml or greater in younger patients confers an increased risk of delayed prostate cancer death. At our institution we have used an aggressive biopsy strategy in younger patients with prostate specific antigen 1 ng/ml or greater. Our objective was to determine the proportion of detected cancer and specifically clinically significant cancer by this strategy. MATERIALS AND METHODS: The prostate biopsy database at Princess Margaret Cancer Centre was queried for patients younger than 50 years who underwent a first prostate biopsy between 2000 and 2016. We included only patients who underwent prostate biopsy due to prostate specific antigen 1 ng/ml or greater and those with a suspicious digital rectal examination, a positive family history or a suspicious lesion on transrectal ultrasound. All clinical and pathological parameters were analyzed. Patients were stratified according to specific prostate specific antigen values. Multivariable logistic regression was performed to ascertain predictors of any prostate cancer diagnosis and of clinically significant prostate cancer. RESULTS: Of the 199 patients who met study inclusion criteria 37 (19%) were diagnosed with prostate cancer and 8 (22%) had a Gleason score of 7 or greater. Of those diagnosed with prostate cancer 25 (68%) had prostate specific antigen 1.5 ng/ml or greater and all men with a Gleason score of 7 or greater had prostate specific antigen 1.5 ng/ml or greater. Notably 19 patients (51%) had prostate cancer exceeding the Epstein criteria for active surveillance. Factors predicting prostate cancer included a positive family history, rising prostate specific antigen and lower prostate volume. CONCLUSIONS: Our results justify adopting an aggressive prostate biopsy strategy in men younger than 50 years with prostate specific antigen 1.5 ng/ml or greater while patients with prostate specific antigen less than 1.5 ng/ml are unlikely to have significant cancer. Special attention should be given to patients with a smaller prostate and a positive family history.

Limitations in Predicting Organ Confined Prostate Cancer in Patients with Gleason Pattern 4 on Biopsy: Implications for Active Surveillance.

PURPOSE: In prostate cancer biopsy Gleason score predicts stage and helps determine active surveillance suitability. Evidence suggests that small incremental differences in the quantitative percent of Gleason pattern 4 on biopsy stratify disease extent, biochemical failure following surgery and eligibility for active surveillance. We explored the overall quantitative percent of Gleason pattern 4 levels and adverse outcomes in patients with low and intermediate risk prostate cancer to whom active surveillance may be offered under expanded criteria. MATERIALS AND METHODS: We analyzed the records of patients with biopsy Gleason score 6 (3 + 3) or 7 (3 + 4) who underwent radical prostatectomy from January 2008 to August 2015. Age, prostate specific antigen, Gleason score, quantitative percent of Gleason pattern 4, overall percent positive cores (percent of prostate cancer) and clinical stage were explored as predictors of nonorgan confined disease and time to failure after radical prostatectomy. RESULTS: In 1,255 patients biopsy Gleason score 7 (3 + 4) was associated with T3 or greater disease at radical prostatectomy in 35.0% compared with Gleason score 6 (3 + 3) in 19.0% (p <0.001). On multivariate analysis for each quantitative percent of Gleason pattern 4 increase there were 2% higher odds of T3 or greater disease (OR 1.02, 95% CI 1.01-1.04, p <0.001). When stratified, patients with Gleason score 7 (3 + 4) only approximated the pT3 rates of Gleason score 6 (3 + 3) when prostate specific antigen was less than 8 ng/ml and the percent of prostate cancer was less than 15%. In those cases the quantitative percent of Gleason pattern 4 had less effect. Time to failure after radical prostatectomy was worse in Gleason score 7 (3 + 4) than 6 (3 + 3) cases. CONCLUSIONS: The quantitative percent of Gleason pattern 4 helps predict advanced disease and Gleason score 7 (3 + 4) is associated with worse outcomes. However, the impact of the quantitative percent of Gleason pattern 4 on adverse pathological and clinical outcomes is best used in combination with prostate specific antigen, age and disease volume since each has a greater impact on predicting nonorgan confined disease. The calculated absolute risk of T3 or greater can be used in shared decision making on prostate cancer treatment by patients and clinicians.

Development and external validation of a biopsy-derived nomogram to predict risk of ipsilateral extraprostatic extension.

OBJECTIVES: To develop and externally validate a nomogram that predicts risk of side-specific extraprostatic extension (EPE) at time of surgery, using commonly available preoperative markers. MATERIALS AND METHODS: A consecutive sample of 753 men treated by radical prostatectomy (RP) at the University Health Network, Toronto, between 2009 and 2015, was used to develop the nomogram. The validation cohort consisted of 311 men treated by RP at Ottawa Hospital Research Institute, between 1992 and 2014. The study outcome was presence of ipsilateral EPE. The association between predictors considered and EPE was tested using univariate and multivariate logistic regression analyses. The predictive accuracy of the nomogram was determined using the area under the receiver-operating characteristic curve. RESULTS: The overall rate of EPE was 19.8% of all lobes in the developmental cohort and 28.9% in the validation cohort. Significant variables in the models were age, prostate-specific antigen and ipsilateral Gleason score, percentage of positive cores and highest core involvement (all P < 0.05). The nomogram predicting risk of EPE had a predictive accuracy of 0.74 in the external validation cohort. CONCLUSION: We developed and externally validated a nomogram that predicts the risk of ipsilateral EPE based on commonly used preoperative markers. This nomogram may be used to assist surgical decision-making prior to RP.

An Increase in Gleason 6 Tumor Volume While on Active Surveillance Portends a Greater Risk of Grade Reclassification with Further Followup.

PURPOSE: We evaluated the relative risk of later grade reclassification and outcomes of patients in whom high volume Gleason 6 prostate cancer develops while on active surveillance. MATERIALS AND METHODS: A prospectively maintained database was used to identify patients on active surveillance between 1998 and 2013. Tumor volume was assessed based on the number of positive cores and proportion of core involvement. The chi-square and Fisher exact tests were used for analysis as appropriate. The primary end point was the development of grade reclassification, defined as grade only and/or grade and volume at the event biopsy. RESULTS: A total of 555 men met the study inclusion criteria. Mean followup was 46 months. Overall 70 patients demonstrated an increase in tumor volume at or after biopsy 2. Compared to those men never experiencing volume or grade reclassification, prostate specific antigen at diagnosis was not significantly different (p=0.95), but median prostate volume was smaller in patients who demonstrated volume reclassification (p <0.001). The incidence of pure volume reclassification was 6.8%, 6.1% and 7.8% at biopsy 2, 3 and 4, respectively. Men with volume reclassification were more likely to experience later grade reclassification than those without at 33.3% vs 9.3%, respectively (p <0.0001). CONCLUSIONS: While Gleason 6 prostate cancer has a favorable natural history, it appears that patients on active surveillance who experience volume reclassification are at substantially higher risk for grade reclassification. Thus, urologists should pay close attention to tumor core involvement, and monitoring should be adjusted accordingly for early volume reclassification in younger men and those in good health.

Congenital limb deficiencies with vascular etiology: Possible association with maternal thrombophilia.

Congenital limb deficiency defects (LDDs) are etiologically heterogeneous. Acquired causes include amniotic bands, teratogens exposure, and chorionic villus sampling before 10 weeks' gestation and intrinsic causes include single-gene disorders and chromosome abnormalities. However, a substantial number of cases, especially terminal transverse deficiency defects, occur without an obvious cause and are ascribed to vascular disruption events. Some studies have found an association between maternal thrombophilia and congenital LDDs. We investigated this association through a review of all prenatally identified LDDs at a major tertiary care center in Toronto, Canada over a 12-year period. Our results showed a higher prevalence of thrombophilias among women with a pregnancy affected with an LDD when compared to the general population [χ2 (3) = 54.63, P < 0.01]. Our research was strengthened by the inclusion of affected pregnancies regardless of outcome, and strict criteria to avoid including LDDs with a non-vascular etiology. Most LDDs were identified during the routine 18-20 week anatomy ultrasound, but some were discovered as early as 13 weeks' gestation. We found an excess of left-sided defects among terminal transverse but not longitudinal deficiencies; additionally, all diagnoses of maternal thrombophilia occurred in the terminal transverse group. Our results support thrombophilia screening in all women with a prenatally diagnosed fetal LDD as well as careful evaluation of the fetal extremities during prenatal ultrasounds in women with a known thrombophilia. © 2016 Wiley Periodicals, Inc.

Choice of Formula and Accuracy of Fetal Weight Estimation in Small-for-Gestational-Age Fetuses.

OBJECTIVES: The purpose of this study was to identify the most accurate sonographic models for fetal weight estimation in specific subgroups of small-for-gestational-age (SGA) fetuses. METHODS: We conducted a retrospective study of women who delivered an SGA neonate and underwent a sonographic estimation of fetal weight within 7 days of delivery in a single tertiary center (n = 370). The accuracy of fetal weight estimation was compared for 33 sonographic models (27 nontargeted and 6 targeted SGA- or low-birth-weight-specific models) in specific subgroups of SGA fetuses: early versus late SGA, asymmetric versus symmetric, and presence of Doppler abnormalities. RESULTS: A wide variation in the accuracy of the different models was found (systematic error, -12.5% to 15.1%; random error, 7.8% to 15.5%). Most nontargeted models tended to systematically overestimate the weight of SGA fetuses. The best performing model in the overall SGA group was the targeted model of Scott et al (J Ultrasound Med 1996; 15:669-672; systematic error ± random error, -2.8% ± 8.3%). However, the optimal models varied for different subgroups of SGA fetuses, and in most cases the targeted models were the most accurate. An approach that used the optimal model for each subgroup of SGA fetuses compared with the uniform use of the model of Scott et al for all SGA fetuses was associated with a lower systematic error (-0.38% versus -2.8%; P < .001) and a higher proportion of weight estimations within 5%, 10%, and 15% of birth weight (48.4% versus 40.8%; P= .038; 78.6% versus 71.4%; P= .022; 95.1% versus 89.2%; P = .003, respectively). CONCLUSIONS: Sonographic models in current use for fetal weight estimation in SGA fetuses have significant errors, and their performance varies for specific subgroups of SGA fetuses. An approach that uses subgroup-specific models may improve the accuracy of weight estimation among SGA fetuses.

Impact of the U.S. Preventive Services Task Force recommendations against prostate specific antigen screening on prostate biopsy and cancer detection rates.

PURPOSE: We determined if the USPSTF recommendation against prostate specific antigen screening was associated with a change in biopsy and cancer detection rates. MATERIALS AND METHODS: We conducted a time series analysis (October 2008 to June 2013) of prostate biopsies performed at University Health Network (Toronto). Biopsies for active surveillance or solely targeting magnetic resonance imaging detected lesions were excluded from study. Interventional ARIMA models with step functions were used to examine changes in the number of biopsies performed and cancers detected per month. Low risk prostate cancer was defined as no Gleason pattern 4 or greater, 3 or fewer cores involved, or 1/3 or less of the total number of cores involved, and no core with greater than 50% cancer involvement. Intermediate to high grade prostate cancer was defined as Gleason 7-10. RESULTS: A total of 3,408 biopsies were performed and 1,601 (47.0%) prostate cancers were detected (low risk prostate cancer 563 [16.5%], intermediate to high grade prostate cancer 914 [26.8%]). The median number of biopsies per month decreased from 58.0 (IQR 54.5-63.0) before the recommendations to 35.5 (IQR 27.0-41.0) afterward (p=0.003), while the median number of patients undergoing first-time biopsy decreased from 42.5 (IQR 37.5-45.5) to 24.0 (IQR 19.0-32.5, p=0.025). The median number of low risk prostate cancers detected per month decreased from 8.5 (IQR 6.5-10.5) to 5.5 (IQR 4.0-7.0, p=0.012), while the median number of intermediate to high grade prostate cancers per month decreased from 17.5 (IQR 14.5-21.5) to 10.0 (IQR 9.0-12.0, p <0.001). CONCLUSIONS: After the USPSTF recommendation the number of biopsies performed (total and first-time), based on referrals from our catchment area, has decreased. This is likely due to decreased use of prostate specific antigen screening. Although it is encouraging that fewer low risk prostate cancers are being diagnosed, the sudden decrease in the detection rate of Gleason 7-10 prostate cancers is concerning.

Regular transition zone biopsy during active surveillance for prostate cancer may improve detection of pathological progression.

PURPOSE: We investigated the frequency of cancer and pathological progression in transition zone biopsies in men undergoing multiple rebiopsies while on active surveillance. MATERIALS AND METHODS: Eligibility criteria of the active surveillance prostate cancer database (1997 to 2012) at our tertiary center includes prostate specific antigen 10 ng/ml or less, cT2 or less, no Gleason grade 4 or 5, 3 or fewer positive cores, no core with greater than 50% involvement, patient age 75 years or less and 1 or more biopsies after initial diagnostic biopsy. We excluded from analysis men with fewer than 10 cores at diagnostic biopsy and/or confirmatory biopsy greater than 24 months after diagnostic biopsy. Multiparametric magnetic resonance imaging was performed selectively to investigate incongruity between prostate specific antigen and biopsy findings. Pathological progression was defined by grade and/or volume (greater than 50% of core involved). Transition zone progression was subdivided into exclusively transition zone and combined transition zone (transition and peripheral zones). A multivariate Cox proportional hazards model was used to determine predictors of transition zone progression. RESULTS: A total of 392 men were considered in analysis. Median followup was 45.5 months. At each biopsy during active surveillance (confirmatory biopsy to biopsy 5+) there were transition zone positive cores in 18.6% to 26.7% of cases, all transition zone progression in 5.9% to 11.1% and exclusively transition zone progression in 2.7% to 6.7%. Volume related progression was noted more frequently than grade related progression (24 vs 9 cases). Predictors of only transition zone progression were the maximum percent in a single core (HR 1.99, 95% CI 1.30-3.04, p = 0.002) and cancer on magnetic resonance imaging (HR 3.19, 95% CI 1.23-8.27, p = 0.02). CONCLUSIONS: Across multiple active surveillance biopsies 2.7% to 6.7% of men had only transition zone progression. We recommend that transition zone biopsy be considered in all men at confirmatory biopsy. Positive magnetic resonance imaging findings or a high percent of core involvement may subsequently be useful to identify patients at risk.

Prospective study of intracranial translucency and the posterior brain in normal fetuses at the 11- to 13-week scan.

OBJECTIVES: To evaluate the ability of sonographers to prospectively identify intracranial translucency and posterior brain structures at 11 to 13 weeks and to evaluate measurement reproducibility of brain stem and brain stem-occipital bone diameters on stored images. METHODS: After specific training for intracranial translucency visualization, 10 nonphysician sonographers prospectively identified intracranial translucency at the 11- to 13-week scan, noting whether intracranial translucency was present, absent, or uncertain. If absent/uncertain, they documented the reason as spina bifida or an inadequate image (with reasons for the inadequate image). Measurements of brain stem and brain stem-occipital bone diameters were performed on stored images. Fifty randomly selected cases were reviewed for intraobserver and interobserver variability. RESULTS: In 313 singleton pregnancies, the posterior brain including intracranial translucency was evaluated; 293 (93.6%) had known pregnancy outcomes. None had open spina bifida, but 7 had chromosomal or congenital abnormalities. In the remaining 286 normal fetuses, intracranial translucency was seen in 275 (96%) and uncertain in 11 (4%), due to inadequate images (top 3 reasons were fetal position [n = 8], obesity [n = 5], and retroverted uterus [n = 4]). Fetal position and gestational age were significantly associated with intracranial translucency visualization (P < .05). Intraobserver and interobserver agreement rates were moderate for measurements of brain stem diameter (intraclass correlation coefficients, 0.59 and 0.57) and substantial for brain stem-occipital bone diameter (intraclass correlation coefficients, 0.76 and 0.61). Bland-Altman analysis revealed negligible intraobserver and interobserver differences in brain stem and brain stem-occipital bone diameter measurements. CONCLUSIONS: Intracranial translucency can be prospectively identified by trained sonographers in 96% of normal fetuses at 11 to 13 weeks. Measurements of brain stem and brain stem-occipital bone diameters are reproducible.

Dyssegmental dysplasia, Silverman-Handmaker type: prenatal ultrasound findings and molecular analysis.

OBJECTIVES: The objective of this study is to describe the prenatal sonographic features and the results of DNA analysis on three fetuses with dyssegmental dysplasia, Silverman-Handmaker type (DD-SH). METHODS: A retrospective review of three fetuses with confirmed DD-SH was conducted. The fetal ultrasound findings, the radiological characteristics, and the results of the mutation analysis of the heparan sulphate perlecan gene 2 (HSPG2) were reviewed. RESULTS: There were three cases in two families with DD-SH diagnosed prenatally. The main prenatal ultrasound and the radiological features of DD-SH were severe limb shortening and vertebral segmentation and fusion defects (anisospondyly). The DNA analysis of the HSPG2 gene showed that the two affected fetuses in a nonconsanguineous family had a compound heterozygote for the c.646G > T transversion in exon 7 and a c.5788C > T transition in exon 46. The fetus born to the consanguineous couple had a homozygous mutation c.1356-27_1507 + 59del. CONCLUSION: DD-SH can be diagnosed prenatally using fetal ultrasound as early as 13 weeks. Xrays and DNA analysis of the HSPG2 gene are important for the confirmation of the diagnosis and for the preimplantation and prenatal diagnosis in pregnancies at risk.

Measurement of peri-prostatic fat thickness using transrectal ultrasonography (TRUS): a new risk factor for prostate cancer.

UNLABELLED: Study Type - Prognosis (cohort) Level of Evidence 2b. What's known on the subject? and What does the study add? ADIPOSE tissue secretes various endocrine and paracrine mediators. Some authors have begun to consider whether peri-prostatic fat (PPF) may interact with the prostate and play a role in carcinogenesis. It has recently been shown that the PPF quantity measured by CT is associated with more aggressive disease in patients undergoing radiation therapy. Our group studied a population not yet diagnosed with prostate cancer. By doing so we were able to identify PPF thickness on transrectal ultrasonography as a risk factor for prostate cancer detection upon biopsy, and as a risk factor for high-grade disease. Our study also raises interesting questions about the underlying mechanisms of the association between PPF quantity and prostate cancer. OBJECTIVE: To determine if the amount of peri-prostatic fat (PPF) on transrectal ultrasonography (TRUS) is a risk factor for incident prostate cancer overall and high-grade prostate cancer (Gleason ≥4). PATIENTS AND METHODS: A prospectively maintained database of patients undergoing prostate biopsy at Princess Margaret Hospital for cancer suspicion was used. • All TRUS examinations were retrospectively reviewed upon 'blinding' to outcome. • PPF thickness, measured as the distance between the prostate and the pubic bone, was used as an index of the quantity of PPF. • PPF measurements, together with other prostate cancer risk factors, were evaluated against prostate cancer and high-grade prostate cancer detection upon biopsy with univariable and multivariable logistic regression and area under the receiver operating characteristic curve (AUC) analysis. RESULTS: Of the 931 patients, 434 (47%) were diagnosed with prostate cancer and 218 (23%) were diagnosed with high-grade prostate cancer. • The mean (range) PPF thickness was 5.3 (0-15) mm. • Increasing PPF thickness was associated with prostate cancer and high-grade prostate cancer diagnosis, with graded effect. When adjusting for other variables, the odds of detecting any prostate cancer and high-grade prostate cancer increased 12% (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.02-1.23) and 20% (OR 1.20, 95% CI 1.07-1.34), respectively, for each millimetre increase in PPF thickness. • The AUCs for the association of PPF with prostate cancer and high-grade prostate cancer were 0.58 (95% CI 0.54-0.62) and 0.59 (95% CI 0.55-0.64), respectively. CONCLUSION: The amount of PPF can be estimated with TRUS and is a predictor of prostate cancer and high-grade prostate cancer at biopsy. To our knowledge, this study is the first to investigate PPF quantity in patients without prior prostate cancer diagnosis.