A Systematic Review and Meta-analysis of the Role of Preoperative MRI in In-breast Tumor Recurrence After Breast-Conserving Surgery.

BACKGROUND: It is unknown whether the identification of additional tumors in the breast using preoperative magnetic resonance imaging (pMRI) results in a lower risk of in-breast tumor recurrence (IBTR) after breast-conserving surgery (BCS). METHODS: A systematic review and meta-analysis of relevant studies were performed. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: From 768 citations, 20 studies met the inclusion criteria for the systematic review. The 20 studies consisted of 14 retrospective reviews, 3 matched cohorts, and 3 randomized controlled trials. Whereas 2 studies reported a statistically significant lower rate of IBTR with pMRI, 18 studies showed no difference, and no studies reported a higher rate. Of the 18 studies showing no significant difference, 12 demonstrated a trend toward a lower IBTR rate in the pMRI group. The criteria for meta-analysis were met by 16 studies. A meta-analysis of 11 studies that reported hazard ratios (HR) for IBTR showed a trend toward a lower rate of IBTR for patients who received preoperative MRI (hazard ratio (HR), 0.89; 95% confidence interval (CI), 0.74-1.05). A meta-analysis of five studies that reported event rates and had similar follow-up duration for both groups demonstrated a lower relative risk (RR) of IBTR (RR, 0.45; 95% CI 0.25-0.81). CONCLUSIONS: Although some evidence supports the hypothesis that identification of additional tumors in the breast using pMRI results in lower rates of IBTR after BCS, the main meta-analysis in this study did not confirm this hypothesis.

A Novel Fetal Magnetic Resonance Imaging Lung Volume Nomogram Stratified by Estimated Fetal Weight.

INTRODUCTION: Fetal magnetic resonance imaging (MRI) lung volume nomograms are increasingly used to prognosticate neonatal outcomes in fetuses with suspected pulmonary hypoplasia. However, pregnancies complicated by fetal anomalies associated with pulmonary hypoplasia may also be complicated by fetal growth restriction (FGR). If a small lung volume is suspected in such cases, it is often unclear whether the lungs are "small" because of underlying lung pathology, or small fetal size. Existing MRI lung volume nomograms have mostly been stratified by gestational age (GA), rather than estimated fetal weight (EFW). Therefore, we aimed to develop a novel fetal lung volume nomogram stratified by EFW. METHODS: Consecutive fetal MRIs performed at a quaternary medical center from 2019 to 2021 were analyzed. MRIs performed due to fetal lung anomalies and cases with FGR were excluded. All MRIs were performed without IV contrast on GE 3 or 1.5 Tesla scanners (GE Healthcare). Images were reviewed by three experienced fetal radiologists. Freehand ROI in square centimeter was drawn around the contours of the lungs on consecutive slices from the apex to the base. The volume of the right, left and total lungs were calculated in mL. Lung volumes were plotted by both EFW and GA. RESULTS: Among 301 MRI studies performed during the study period, 170 cases met inclusion criteria and were analyzed. MRIs were performed between 19- and 38-week gestation, and a sonographic EFW was obtained within a mean of 2.9 days (SD ± 5.5 days, range 0-14 days) of each MRI. Nomograms stratified by both EFW and GA were created using 200 g. and weekly intervals respectively. A formula using EFW to predict total lung volume was calculated: LV = 0.07497804 EFW0.88276 (R2 = 0.87). CONCLUSIONS: We developed a novel fetal lung volume nomogram stratified by EFW. If validated, this nomogram may assist clinicians predict outcomes in cases of fetal pulmonary hypoplasia with concomitant FGR.

Reasons for Long-term Opioid Prescriptions After Guideline-directed Opioid Prescribing and Excess Opioid Pill Disposal.

OBJECTIVES: The aim of this study was to determine the frequency and reasons for long-term opioid prescriptions (rxs) after surgery in the setting of guideline-directed prescribing and a high rate of excess opioid disposal. BACKGROUND: Although previous studies have demonstrated that 5% to 10% of opioid-naïve patients prescribed opioids after surgery will receive long-term (3-12 months after surgery) opioid rxs, little is known about the reasons why long-term opioids are prescribed. METHODS: We studied 221 opioid-naïve surgical patients enrolled in a previously reported prospective clinical trial which used a patient-centric guideline for discharge opioid prescribing and achieved a high rate of excess opioid disposal. Patients were treated on a wide variety of services; 88% of individuals underwent cancer-related surgery. Long-term opioid rxs were identified using a Prescription Drug Monitoring Program search and reasons for rxs and opioid adverse events were ascertained by medical record review. We used a consensus definition for persistent opioid use: opioid rx 3 to 12 months after surgery and >60day supply. RESULTS: 15.3% (34/221) filled an opioid rx 3 to 12 months after surgery, with 5.4% and 12.2% filling an rx 3 to 6 and 6 to 12 months after surgery, respectively. The median opioid rx days supply per patient was 7, interquartile range 5 to 27, range 1 to 447 days. The reasons for long-term opioid rxs were: 51% new painful medical condition, 40% new surgery, 6% related to the index operation; only 1 patient on 1 occasion was given an opioid rx for a nonspecific reason. Five patients (2.3%) developed persistent opioid use, 2 due to pain from recurrent cancer, 2 for new medical conditions, and 1 for a chronic abscess. CONCLUSIONS: In a group of prospectively studied opioid-naïve surgical patients discharged with guideline-directed opioid rxs and who achieved high rates of excess opioid disposal, no patients became persistent opioid users solely as a result of the opioid rx given after their index surgery. Long-term opioid use did occur for other, well-defined, medical or surgical reasons.

Breast-Conserving Surgery Margin Guidance Using Micro-Computed Tomography: Challenges When Imaging Radiodense Resection Specimens.

BACKGROUND: Breast-conserving surgery (BCS) is an integral component of early-stage breast cancer treatment, but costly reexcision procedures are common due to the high prevalence of cancer-positive margins on primary resections. A need exists to develop and evaluate improved methods of margin assessment to detect positive margins intraoperatively. METHODS: A prospective trial was conducted through which micro-computed tomography (micro-CT) with radiological interpretation by three independent readers was evaluated for BCS margin assessment. Results were compared to standard-of-care intraoperative margin assessment (i.e., specimen palpation and radiography [abbreviated SIA]) for detecting cancer-positive margins. RESULTS: Six hundred margins from 100 patients were analyzed. Twenty-one margins in 14 patients were pathologically positive. On analysis at the specimen-level, SIA yielded a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 42.9%, 76.7%, 23.1%, and 89.2%, respectively. SIA correctly identified six of 14 margin-positive cases with a 23.5% false positive rate (FPR). Micro-CT readers achieved sensitivity, specificity, PPV, and NPV ranges of 35.7-50.0%, 55.8-68.6%, 15.6-15.8%, and 86.8-87.3%, respectively. Micro-CT readers correctly identified five to seven of 14 margin-positive cases with an FPR range of 31.4-44.2%. If micro-CT scanning had been combined with SIA, up to three additional margin-positive specimens would have been identified. DISCUSSION: Micro-CT identified a similar proportion of margin-positive cases as standard specimen palpation and radiography, but due to difficulty distinguishing between radiodense fibroglandular tissue and cancer, resulted in a higher proportion of false positive margin assessments.

Real-time ultrasound-derived fat fraction in pediatric population: feasibility validation with MR-PDFF.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. To avoid limitations of liver biopsy and MRI, quantitative ultrasound has become a research focus. Ultrasound-derived fat fraction (UDFF) is based on a combination of backscatter coefficient and attenuation parameter. OBJECTIVE: The objectives of the study were to determine (1) agreement between UDFF/MRI proton density fat fraction (MR-PDFF) and (2) whether BMI and age are predictive for UDFF. MATERIALS AND METHODS: This cross-sectional prospective study included a convenience sample of 46 children referred for clinically indicated abdominal MRI. MR-PDFF and five acquisitions of UDFF were collected. Intraclass correlation coefficient (ICC) and Bland-Altman analysis were used to assess agreement between MR-PDFF and UDFF. Receiver operating characteristic curves were calculated for UDFF prediction of liver steatosis (MR-PDFF ≥ 6%). Multivariable regression was performed to assess BMI and age as predictors for UDFF. RESULTS: Twenty-two participants were male, 24 were female, and the mean age was 14 ± 3 (range: 7-18) years. Thirty-six out of 46 participants had normal liver fat fraction <6%, and 10/46 had liver steatosis. UDFF was positively associated with MR-PDFF (ICC 0.92 (95% CI, 0.89-0.96). The mean bias between UDFF and MR-PDFF was 0.64% (95% LOA, -5.3-6.6%). AUROC of UDFF for steatosis was of 0.95 (95% CI, 0.89-0.99). UDFF cutoff of 6% had a sensitivity of 90% (95% CI, 55-99%) and a specificity of 94% (95% CI, 81-0.99%). BMI was an independent predictor of UDFF (correlation: 0.55 (95% CI, 0.35-0.95)). CONCLUSIONS: UDFF shows strong agreement with MR-PDFF in children. A UDFF cutoff of 6% provides good sensitivity and specificity for detection of MR-PDFF of ≥ 6%.

The impact of shoulder pathology on individuals with distal radius fracture.

BACKGROUND: Shoulder pathology can occur concurrently with a distal radius fracture (DRF) but few studies have examined this population. PURPOSE: The purpose of this study was to expand the understanding of the impact of shoulder pathology on individuals with DRF. STUDY DESIGN: Mixed Methods Design. METHODS: A total of 45 participants with a DRF were categorized into a DRF only (n = 29) and shoulder pathology concurrent with DRF (SPCDRF) (n = 16) groups. Quantitative data gathered included demographics, Quick Disabilities of the Arm, Shoulder, and Hand, Tampa Scale of Kinesiophobia-11, Visual Analog Scale, and Compensatory Mechanism Checklist. Qualitative interviews were performed with 7 participants in the SPCDRF group. Within group correlations were analyzed via the Spearman Rank. The Mann Whitney U test was used to compare the two groups. Qualitative analysis was performed to describe the experience of participants in the SPCDRF group. A mixed methods analysis compared quantitative and qualitative data. RESULTS: Sixteen participants (35.6%) in the sample presented with shoulder pathology; 6 participants (37.5%) presented at initial evaluation due to the fall; 10 participants (62.5%) developed shoulder pathology due to compensation or disuse. Average number of days to develop shoulder pathology after the DRF was 43 days. SPCDRF participants had significantly greater pain levels (p = .02) and more activity avoidance (p = .03) than the DRF only group. Four qualitative themes emerged: It's difficult to perform occupations and changes had to be made; There is fear and uncertainty; The impact of pain; Tried to be normal but could not Mixed methods analysis found that qualitative data further illuminated quantitative findings. CONCLUSIONS: Individuals with shoulder pathology concurrent with a DRF may present with higher pain levels and avoid activity more. In addition, they may describe fearfulness in using their injured upper extremity especially if they have high levels of pain. STUDY DESIGN: Mixed Methods Design.

Opioid Dependence and Overdose After Surgery: Rate, Risk Factors, and Reasons.

OBJECTIVE: To determine: (1) incidence of " opioid never events " ( ONEs ), defined as the development of opioid dependence or overdose in an opioid-naive surgical patient who is prescribed opioids postoperatively and (2) risk factors predicting ONEs. BACKGROUND: Patients receiving opioids after surgery are at risk of experiencing life-threatening opioid-related adverse events. METHODS: An electronic medical record review identified surgical patients at an academic medical center between January 1, 2015, and December 31, 2018, followed through March 31, 2020. ONEs were determined by International Classification of Diseases, Ninth/10th Revision (ICD-9/10) codes, and electronic medical record review. RESULTS: A total of 35,335 opioid-naive surgical patients received a perioperative opioid prescription. The median follow-up was 3.47 years (range: 1.25-5.25 years). ONEs occurred in 0.19% (67/35,335) of patients. The ONE rate was 5.6 per 10,000 person-years of follow-up. Ten of 67 ONE patients overdosed on opioids. The median time to ONE was 1.6 years; the highest ONE rate was observed 1 to 2 years after surgery. In multivariate analysis, patients receiving opioid prescriptions 90 to 180 or 90 to 360 days after surgery had the highest risk of developing ONEs [hazard ratio (HR)=6.39, confidence interval (CI): 3.72-10.973; HR=6.87, CI: 4.24-11.12, respectively]. Surgical specialty (HR=5.21, 2.65-0.23) and patient age (HR=4.17, CI: 2.50-6.96) were also risk factors for ONEs. Persistent opioid use 90 to 360 days after surgery was present in 45% of patients developing ONEs. CONCLUSIONS: Postoperative opioid dependence or overdose is a significant health problem, affecting roughly 2 per 1000 opioid-naive surgical patients prescribed an opioid and followed for 5 years. Risk factors for the development of ONEs include opioid use 3 to 12 months after surgery, patient age, and surgical procedure.

Surgery Prescription Opioid Misuse and Diversion in US Adults and Associated Risk Factors.

INTRODUCTION: To justify a practice change, it is critical to determine if opioids prescribed after surgery, surgery prescription (Rx) opioids, are in fact associated with opioid misuse and diversion. Currently, there is only limited data to support this assumption. METHODS: We administered a 40-question survey to US adults (18+) who had received a surgery Rx opioid within the last 5 y on Amazon Mechanical Turk, an online crowdsourcing worksite. Incidence and risk factors for surgery Rx opioid misuse, self-reported taking of surgery Rx opioids in a way other than instructed by a provider, and diversion, self-reported having one's surgery Rx opioids shared, sold, or stolen, were analyzed. The government validated Opioid Risk Tool (ORT) was used. RESULTS: A total of 966 participants from all 50 states met inclusion: 52% were male, 43% were aged 30-39 y, and 79% self-identified as white. Overall, 34% (n = 333) of respondents reported misusing their surgery Rx opioids and risk factors included working in healthcare, scoring high on the ORT, experiencing an elevated mood with opioids, refilling a Rx, and keeping leftover pills. A total of 22% (n = 212) reported diverting their surgery Rx opioids, and risk factors included working in healthcare, scoring high on the ORT, undergoing plastic surgery, refilling a Rx, and keeping leftover pills. CONCLUSIONS: Rates of surgery Rx opioid misuse and diversion in the US may be as high as one in three and one in five adults, respectively. Efforts to improve leftover pill disposal and risk stratification for prescribing patterns may help to mitigate risk.

What matters most: Randomized controlled trial of breast cancer surgery conversation aids across socioeconomic strata.

BACKGROUND: Women of lower socioeconomic status (SES) with early-stage breast cancer are more likely to report poorer physician-patient communication, lower satisfaction with surgery, lower involvement in decision making, and higher decision regret compared to women of higher SES. The objective of this study was to understand how to support women across socioeconomic strata in making breast cancer surgery choices. METHODS: We conducted a 3-arm (Option Grid, Picture Option Grid, and usual care), multisite, randomized controlled superiority trial with surgeon-level randomization. The Option Grid (text only) and Picture Option Grid (pictures plus text) conversation aids were evidence-based summaries of available breast cancer surgery options on paper. Decision quality (primary outcome), treatment choice, treatment intention, shared decision making (SDM), anxiety, quality of life, decision regret, and coordination of care were measured from T0 (pre-consultation) to T5 (1-year after surgery. RESULTS: Sixteen surgeons saw 571 of 622 consented patients. Patients in the Picture Option Grid arm (n = 248) had higher knowledge (immediately after the visit [T2] and 1 week after surgery or within 2 weeks of the first postoperative visit [T3]), an improved decision process (T2 and T3), lower decision regret (T3), and more SDM (observed and self-reported) compared to usual care (n = 257). Patients in the Option Grid arm (n = 66) had higher decision process scores (T2 and T3), better coordination of care (12 weeks after surgery or within 2 weeks of the second postoperative visit [T4]), and more observed SDM (during the surgical visit [T1]) compared to usual care arm. Subgroup analyses suggested that the Picture Option Grid had more impact among women of lower SES and health literacy. Neither intervention affected concordance, treatment choice, or anxiety. CONCLUSIONS: Paper-based conversation aids improved key outcomes over usual care. The Picture Option Grid had more impact among disadvantaged patients. LAY SUMMARY: The objective of this study was to understand how to help women with lower incomes or less formal education to make breast cancer surgery choices. Compared with usual care, a conversation aid with pictures and text led to higher knowledge. It improved the decision process and shared decision making (SDM) and lowered decision regret. A text-only conversation aid led to an improved decision process, more coordinated care, and higher SDM compared to usual care. The conversation aid with pictures was more helpful for women with lower income or less formal education. Conversation aids with pictures and text helped women make better breast cancer surgery choices.

Effect of intraoperative secretin on operative outcomes in pancreatic resection: A randomized controlled trial.

BACKGROUND: Objectives: We performed a randomized, double-blind, placebo-controlled trial to determine if using Secretin intra-operatively to identify leaks and subsequently target operative intervention would decrease the frequency of clinically significant post-operative pancreatic fistula formation. METHODS: Patients undergoing pancreaticoduodenectomy or distal pancreatectomy were randomized to receive intra-operative Secretin or placebo intra-operatively following the completed pancreaticojejunostomy or closure of the cut remnant stump. If a potential leak was identified, targeted therapy with directed suture placement was performed. RESULTS: 170 patients were randomized; 83 receiving placebo and 87 receiving Secretin. The rate of clinically significant fistula formation was 3% (3/87) in the Secretin group and 6% (5/83) in the placebo group (p = 0.489). The rate of biochemical leak was 29% (25/87) in the Secretin group and 19% (16/83) in the placebo group (p = 0.157). There were no Grade C post-operative fistula in either group. Of the 9% of patients in the Secretin group who had a targeted intra-operative intervention, none developed a clinically significant fistula. Adverse events were similar between groups. CONCLUSIONS: Compared to placebo, intra-operative Secretin administration was not associated with an overall reduction in clinically significant pancreatic fistula formation. However, patients with an intra-operative leak identified by Secretin may benefit from intervention (clinicaltrials.gov: NCT02160808).

Liver Fat Quantification by Ultrasound in Children: A Prospective Study.

BACKGROUND. Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children in certain regions and is rising in prevalence with increasing obesity. Accurate noninvasive imaging methods for diagnosing and quantifying liver fat are needed to guide NAFLD management. OBJECTIVE. The purpose of this article is to evaluate four ultrasound technologies for quantitative assessment of liver fat content in children using MRI proton density fat fraction (PDFF) as a reference standard. METHODS. This prospective study enrolled children who underwent clinical abdominal MRI without general anesthesia between November 2018 and July 2019. Patients underwent investigational liver ultrasound within a day of 1.5-T or 3-T MRI. Acquired ultrasound radiofrequency data were processed offline to compute the acoustic attenuation coefficient, hepatorenal index (HRI), Nakagami parameter, and shear-wave elastography (SWE) parameters (elasticity, viscosity, and dispersion). Ultrasound parameters were compared with MRI PDFF obtained using a multiecho sequence. A second observer independently performed offline attenuation coefficient and HRI measurements in all patients. RESULTS. A total of 48 patients were enrolled: 22 girls, 26 boys; mean age of 13 years (range, 7-17 years); mean body mass index (weight in kilograms divided by the square of height in meters) of 22.25 (range, 14.5-48.1). A total of 21% (10/48) had steatosis (PDFF ≥ 5%). PDFF was correlated with attenuation coefficient (r = 0.76; 95% CI, 0.60-0.86; p < .001), HRI (r = 0.84; 95% CI, 0.74-0.91; p < .001), and Nakagami parameter (r = 0.55, 95% CI, 0.32-0.72, p < .001), but not SWE parameters (r = 0.05-0.25; p > .05). In patients with no, mild, moderate, and severe steatosis according to PDFF, the mean (± SD) attenuation coefficient was 0.48 ± 0.08, 0.54 ± 0.03, 0.57 ± 0.04, and 0.86 ± 0.07 dB/cm/MHz, respectively, and the mean HRI was 1.28 ± 0.30, 1.59 ± 0.23, 2.25 ± 0.04, and 3.06 ± 0.49, respectively. For the attenuation coefficient, the threshold of 0.54 dB/cm/MHz achieved a sensitivity of 80% and a specificity of 82% for steatosis, and 0.60 dB/cm/MHz achieved a sensitivity of 80% and a specificity of 98% for moderate steatosis. For HRI, the threshold of 1.48 achieved sensitivity of 90% and specificity of 76% for steatosis, and 2.11 achieved sensitivity of 100% and specificity of 100% for moderate steatosis. The interobserver concordance coefficient was 0.92 for attenuation coefficient and 0.91 for HRI. CONCLUSION. Attenuation coefficient and HRI accurately detected and quantified liver fat in this small sample of children. CLINICAL IMPACT. Quantitative ultrasound parameters may guide NAFLD diagnosis and management in children.

Ultrasound shear wave elastography: does it add value to gray-scale ultrasound imaging in differentiating biliary atresia from other causes of neonatal jaundice?

BACKGROUND: Neonatal/infantile jaundice is relatively common, and most cases resolve spontaneously. However, in the setting of unresolved neonatal cholestasis, a prompt and accurate assessment for biliary atresia is vital to prevent poor outcomes. OBJECTIVE: To determine whether shear wave elastography (SWE) alone or combined with gray-scale imaging improves the diagnostic performance of US in discriminating biliary atresia from other causes of neonatal jaundice over that of gray-scale imaging alone. MATERIALS AND METHODS: Infants referred for cholestatic jaundice were assessed with SWE and gray-scale US. On gray-scale US, two radiology readers assessed liver heterogeneity, presence of the triangular cord sign, hepatic artery size, presence/absence of common bile duct and gallbladder, and gallbladder shape; associated interobserver correlation coefficients (ICC) were calculated. SWE speeds were performed on a Siemens S3000 using 6C2 and 9 L4 transducers with both point and two-dimensional (2-D) SWE US. Both univariable and multivariable analyses were performed, as were receiver operating characteristic curves (ROC) and statistical significance tests (chi-squared, analysis of variance, t-test and Wilcoxon rank sum) when appropriate. RESULTS: There were 212 infants with biliary atresia and 106 without biliary atresia. The median shear wave speed (SWS) for biliary atresia cases was significantly higher (P<0.001) than for non-biliary-atresia cases for all acquisition modes. For reference, the median L9 point SWS was 2.1 m/s (interquartile range [IQR] 1.7-2.4 m/s) in infants with biliary atresia and 1.5 m/s (IQR 1.3-1.9 m/s) in infants without biliary atresia (P<0.001). All gray-scale US findings were significantly different between biliary-atresia and non-biliary-atresia cohorts (P<0.001), intraclass correlation coefficient (ICC) range 0.7-1.0. Triangular cord sign was most predictive of biliary atresia independent of other gray-scale findings or SWS - 96% specific and 88% sensitive. Multistep univariable/multivariable analysis of both gray-scale findings and SWE resulted in three groups being predictive of biliary atresia likelihood. Abnormal common bile duct/gallbladder and enlarged hepatic artery were highly predictive of biliary atresia independent of SWS (100% for girls and 95-100% for boys). Presence of both the common bile duct and the gallbladder along with a normal hepatic artery usually excluded biliary atresia independent of SWS. Other gray-scale combinations were equivocal, and including SWE improved discrimination between biliary-atresia and non-biliary-atresia cases. CONCLUSION: Shear wave elastography independent of gray-scale US significantly differentiated biliary-atresia from non-biliary-atresia cases. However, gray-scale findings were more predictive of biliary atresia than elastography. SWE was useful for differentiating biliary-atresia from non-biliary-atresia cases in the setting of equivocal gray-scale findings.

Clinical use of shear-wave elastography for detecting liver fibrosis in children and adolescents with cystic fibrosis.

BACKGROUND: Complications from liver cirrhosis are a leading cause of death in children with cystic fibrosis. Identifying children at risk for developing liver cirrhosis and halting its progression are critical to reducing liver-associated mortality. OBJECTIVE: Quantitative US imaging, such as shear-wave elastography (SWE), might improve the detection of liver fibrosis in children with cystic fibrosis (CF) over gray-scale US alone. We incorporated SWE in our pediatric CF liver disease screening program and evaluated its performance using magnetic resonance (MR) elastography. MATERIALS AND METHODS: Ninety-four children and adolescents with CF underwent 178 SWE exams, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and platelet measurements. Of these, 27 children underwent 34 MR elastography exams. We evaluated SWE performance using 6-MHz and 9-MHZ point SWE, and 9-MHz two-dimensional (2-D) SWE. RESULTS: The 6-MHz point SWE was the only method that correlated with MR elastography (r=0.52; 95% confidence interval [CI] 0.20-0.74; P=0.003). SWE of 1.45 m/s distinguished normal from abnormal MR elastography (79% sensitivity, 100% specificity, 100% positive predictive value [PPV], 55% negative predictive value [NPV], area under the receiver operating characteristic [AUROC] curve 0.94). SWE of 1.84 m/s separated mild-moderate (3.00-4.77 kPa) from severe (>4.77 kPa) MR elastography (88% sensitivity, 86% specificity, 78% PPV, 93% NPV, AUROC 0.79). Elevations of AST, ALT, GGT and thrombocytopenia were associated with higher SWE. AST-to-platelet ratio index of 0.42, fibrosis-4 of 0.29, and GGT-to-platelet ratio of 1.43 all had >95% NPV for SWE >1.84 m/s. CONCLUSION: Given its correlation with MR elastography, SWE might be a clinically useful predictor of liver fibrosis. We identified imaging criteria delineating the use of SWE to identify increased liver stiffness in children with CF. With multicenter validation, these data might be used to improve the detection and monitoring of liver fibrosis in children with CF.

Contrast-enhanced ultrasound of blunt abdominal trauma in children.

Trauma is the leading cause of morbidity and mortality in children, and rapid identification of organ injury is essential for successful treatment. Contrast-enhanced ultrasound (CEUS) is an appealing alternative to contrast-enhanced CT in the evaluation of children with blunt abdominal trauma, mainly with respect to the potential reduction of population-level exposure to ionizing radiation. This is particularly important in children, who are more vulnerable to the hazards of ionizing radiation than adults. CEUS is useful in hemodynamically stable children with isolated blunt low- to moderate-energy abdominal trauma to rule out solid organ injuries. It can also be used to further evaluate uncertain contrast-enhanced CT findings, as well as in the follow-up of conservatively managed traumatic injuries. CEUS can be used to detect abnormalities that are not apparent by conventional US, including infarcts, pseudoaneurysms and active bleeding. In this article we present the current experience from the use of CEUS for the evaluation of pediatric blunt abdominal trauma, emphasizing the examination technique and interpretation of major abnormalities associated with injuries in the liver, spleen, kidneys, adrenal glands, pancreas and testes. We also discuss the limitations of the technique and offer a review of the major literature on this topic in children, including an extrapolation of experience from adults.

Starting a pediatric contrast ultrasound service: made simple!

The addition of contrast US to an existing pediatric US service requires several preparatory steps. This overview provides a guide to simplify the process. Initially, it is important to communicate to all stakeholders the justifications for pediatric contrast US, including (1) its comparable or better diagnostic results relative to other modalities; (2) its reduction in procedural sedation or anesthesia by avoiding MRI or CT; (3) its reduction or elimination of radiation exposure by not having to perform fluoroscopy or CT; (4) the higher safety profile of US contrast agents (UCA) compared to other contrast agents; (5) the improved exam comfort and ease inherent to US, leading to better patient and family experience, including bedside US exams for children who cannot be transported; (6) the need for another diagnostic option in light of increasing demand by parents and providers; and (7) its status as an approved and reimbursable exam. It is necessary to have an UCA incorporated into the pharmacy formulary noting that only SonoVue/Lumason is currently approved for pediatric use. In the United States this UCA is approved for intravenous administration for cardiac and liver imaging and for vesicoureteric reflux detection with intravesical application. In Europe and China it is only approved for the intravesical use in children. All other applications are off-label. The US scanner needs to be equipped with contrast-specific software. The UCA has to be prepared just before the exam and it is important to strictly follow the steps as outlined in the packaging inserts in order to prevent premature destruction of the microbubbles. The initial training in contrast US is best focused on the frontline staff actually performing the US studies; these might be sonographers, pediatric or interventional radiologists, or trainees. It is important from the outset to educate the referring physicians about contrast US. It is helpful to participate in existing contrast US courses, particularly those with hands-on components.

Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma.

BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. RESULTS: Immediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in the per-protocol analysis. In the per-protocol analysis, the mean (±SE) 3-year rate of melanoma-specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively; P=0.42 by the log-rank test) at a median follow-up of 43 months. The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively; P=0.05 by the log-rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%; P<0.001 by the log-rank test); these results must be interpreted with caution. Nonsentinel-node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence (hazard ratio, 1.78; P=0.005). Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. CONCLUSIONS: Immediate completion lymph-node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma-specific survival among patients with melanoma and sentinel-node metastases. (Funded by the National Cancer Institute and others; MSLT-II ClinicalTrials.gov number, NCT00297895 .).

The shape of breast cancer.

PURPOSE: Little is known about the three-dimensional shape of breast cancer. Implicit to approaches that localize the center of the tumor for breast-conserving surgery (BCS) of non-palpable cancers is the assumption that breast cancers are spherical about a central point, which may not be accurate. METHODS: Pre-operative supine breast MRI images were obtained of 83 breast cancer patients undergoing partial mastectomy using supine MRI-guided resection techniques. Three-dimensional (3D) tumor models were derived after radiologists outlined tumor edges on successive MRI slices. Ideal resection volumes were determined by adding 1 cm in every dimension to the actual tumor volume. Geometrically defined parameters were used to define tumor shapes and associations between clinical variables and shapes were examined. RESULTS: Seventy-five patients had invasive cancer. Breast cancers were categorized into four tumor shapes: 34% of tumors were discoidal, 29% segmental, 19% spherical, and 18% irregular. If hypothetical spherical excisions were performed, non-spherical cases would excise 143% more tissue than the ideal resection volume. When the 3D shape of each tumor was provided to the surgeon during MR-guided BCS, the percentage of tissue overexcised in non-spherical cases was significantly less (143% vs. 66%, p < 0.001). CONCLUSIONS: Information obtained from a supine MRI can be used to generate 3D tumor models and rapidly classify breast tumor shapes. The vast majority of invasive cancers and DCIS are not spherical. Knowledge of tumor shape may allow surgeons to excise breast cancer more precisely.

Plasma DNA as a "liquid biopsy" incompletely complements tumor biopsy for identification of mutations in a case series of four patients with oligometastatic breast cancer.

PURPOSE: Circulating tumor DNA in plasma may present a minimally invasive opportunity to identify tumor-derived mutations to inform selection of targeted therapies for individual patients, particularly in cases of oligometastatic disease where biopsy of multiple tumors is impractical. To assess the utility of plasma DNA as a "liquid biopsy" for precision oncology, we tested whether sequencing of plasma DNA is a reliable surrogate for sequencing of tumor DNA to identify targetable genetic alterations. METHODS: Blood and biopsies of 1-3 tumors were obtained from 4 evaluable patients with advanced breast cancer. One patient provided samples from an additional 7 tumors post-mortem. DNA extracted from plasma, tumor tissues, and buffy coat of blood were used for probe-directed capture of all exons in 149 cancer-related genes and massively parallel sequencing. Somatic mutations in DNA from plasma and tumors were identified by comparison to buffy coat DNA. RESULTS: Sequencing of plasma DNA identified 27.94 ± 11.81% (mean ± SD) of mutations detected in a tumor(s) from the same patient; such mutations tended to be present at high allelic frequency. The majority of mutations found in plasma DNA were not found in tumor samples. Mutations were also found in plasma that matched clinically undetectable tumors found post-mortem. CONCLUSIONS: The incomplete overlap of genetic alteration profiles of plasma and tumors warrants caution in the sole reliance of plasma DNA to identify therapeutically targetable alterations in patients and indicates that analysis of plasma DNA complements, but does not replace, tumor DNA profiling. TRIAL REGISTRATION: Subjects were prospectively enrolled in trial NCT01836640 (registered April 22, 2013).

Short-term Preoperative Diet Decreases Bleeding After Partial Hepatectomy: Results From a Multi-institutional Randomized Controlled Trial.

BACKGROUND: Our previous case series suggested that a 1-week, low-calorie and low-fat diet was associated with decreased intraoperative blood loss in patients undergoing liver surgery. OBJECTIVE: The current study evaluates the effect of this diet in a randomized controlled trial. METHODS: We randomly assigned 60 patients with a body mass index ≥25 kg/m(2) to no special diet or an 800-kcal, 20 g fat, and 70 g protein diet for 1 week before liver resection. Surgeons were blinded to diet assignment. Hepatic glycogen stores were evaluated using periodic acid Schiff (PAS) stains. RESULTS: Ninety four percent of the patients complied with the diet. The diet group consumed fewer daily total calories (807 vs 1968 kcal, P < 0.001) and fat (21 vs 86 g, P < 0.001) than the no diet group. Intraoperative blood loss was less in the diet group: mean blood loss 452 vs 863 mL (P = 0.021). There was a trend towards decreased transfusion in the diet group (138 vs 322 mL, P = 0.06). The surgeon judged the liver to be easier to manipulate in the diet group: 1.86 versus 2.90, P = 0.004. Complication rate (20% vs 17%), length of stay (median 5 vs 4 days) and mortality did not differ between groups. There was no difference in hepatic steatosis between groups. There was less glycogen in hepatocytes in the diet group (PAS stain score 1.61 vs 2.46, P < 0.0001). CONCLUSIONS: A short-course, low-fat, and low-calorie diet significantly decreases bleeding and makes the liver easier to manipulate in hepatic surgery.

Prospective Assessment of Ultrasound Shear Wave Elastography for Discriminating Biliary Atresia from other Causes of Neonatal Cholestasis.

OBJECTIVE: To prospectively assess the diagnostic performance of ultrasound shear wave elastography (SWE) and hepatobiliary laboratory biomarkers for discriminating biliary atresia from other causes of neonatal cholestasis. STUDY DESIGN: Forty-one patients <3 months of age with neonatal cholestasis (direct bilirubin >2 mg/dL) and possible biliary atresia were prospectively enrolled. Both 2-dimensional (2D) and point ultrasound SWE were performed prior to knowing the final diagnosis. Median 2D (8) and point (10) shear wave speed measurements were calculated for each subject and used for analyses. The Mann-Whitney U test was used to compare shear wave speed and laboratory measurements between patients with and without biliary atresia. Receiver operating characteristic curve analyses and multivariable logistic regression were used to evaluate diagnostic performance. RESULTS: Thirteen subjects (31.7%) were diagnosed with biliary atresia, and 28 subjects (68.3%) were diagnosed with other causes of neonatal cholestasis. Median age at the time of ultrasound SWE was 37 days. Median 2D (2.08 vs 1.49 m/s, P = .0001) and point (1.95 vs 1.21 m/s, P = .0014) ultrasound SWE measurements were significantly different between subjects with and without biliary atresia. Using a cut-off value of >1.84 m/s, 2D ultrasound SWE had a sensitivity = 92.3%, specificity = 78.6%, and area under the receiver operating characteristic curve (AuROC) of 0.89 (P < .0001). Using a cut-off value of >320 (U/L), gamma-glutamyl transferase (GGT) had a sensitivity = 100.0%, specificity = 77.8%, and AuROC of 0.85 (P < .0001). Multivariable logistic regression demonstrated an AuROC of 0.93 (P < .0001), with 2 significant covariates (2D ultrasound SWE [OR = 23.06, P = .01]; GGT [OR = 1.003, P = .036]). CONCLUSIONS: Ultrasound SWE and GGT can help discriminate biliary atresia from other causes of neonatal cholestasis.