Assessment of Radiology Artificial Intelligence Software: A Validation and Evaluation Framework.

Artificial intelligence (AI) software in radiology is becoming increasingly prevalent and performance is improving rapidly with new applications for given use cases being developed continuously, oftentimes with development and validation occurring in parallel. Several guidelines have provided reporting standards for publications of AI-based research in medicine and radiology. Yet, there is an unmet need for recommendations on the assessment of AI software before adoption and after commercialization. As the radiology AI ecosystem continues to grow and mature, a formalization of system assessment and evaluation is paramount to ensure patient safety, relevance and support to clinical workflows, and optimal allocation of limited AI development and validation resources before broader implementation into clinical practice. To fulfil these needs, we provide a glossary for AI software types, use cases and roles within the clinical workflow; list healthcare needs, key performance indicators and required information about software prior to assessment; and lay out examples of software performance metrics per software category. This conceptual framework is intended to streamline communication with the AI software industry and provide healthcare decision makers and radiologists with tools to assess the potential use of these software. The proposed software evaluation framework lays the foundation for a radiologist-led prospective validation network of radiology AI software. Learning Points: The rapid expansion of AI applications in radiology requires standardization of AI software specification, classification, and evaluation. The Canadian Association of Radiologists' AI Tech & Apps Working Group Proposes an AI Specification document format and supports the implementation of a clinical expert evaluation process for Radiology AI software.

Prospective Evaluation of Virtual MR Elastography With Diffusion-Weighted Imaging in Subjects With Nonalcoholic Fatty Liver Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is increasingly common worldwide and can lead to the development of cirrhosis, liver failure and cancer. Virtual magnetic resonance elastography (VMRE), which is based on a shifted apparent diffusion coefficient (sADC), is a potential noninvasive method to assess liver fibrosis without the specialized hardware and expertise required to implement traditional MR elastography (MRE). Although hepatic steatosis is known to confound ADC measurements, previous studies using VMRE have not corrected for hepatic fat fraction. PURPOSE: To compare VMRE, corrected for the confounding effects of unsuppressed fat signal, to MRE and biopsy in subjects with suspected NAFLD. STUDY TYPE: Prospective, cross-sectional. POPULATION: A total of 49 adult subjects with suspected NAFLD (18 male; median age 55 years, range 33-74 years) who underwent liver biopsy. FIELD STRENGTH/SEQUENCE: 3T, diffusion-weighted spin echo planar, chemical-shift encoded (IDEAL IQ) and MRE sequences. ASSESSMENT: Two observers drew regions of interest on sADC, proton density fat fraction and MRE-derived stiffness maps. Fat-corrected sADC values were used to calculate the diffusion-based shear modulus according to the VMRE method. Predicted fibrosis stage for MRE and VMRE was determined using previously published cut-off values. STATISTICAL TESTS: The relationship between VMRE and MRE was assessed with least-squares linear regression (coefficient of determination, R2 ). Agreement between MRE and VMRE-predicted fibrosis stage was evaluated with a kappa coefficient and accuracy compared using McNemar's test. A one-way ANOVA determined if the fat-corrected sADC (VMRE) and MRE differed by fibrosis stage. A P value < 0.05 was considered statistically significant. RESULTS: Least squares regression of VMRE vs. MRE revealed R2  = 0.046 and a slope that was not significantly different from zero (P = 0.14). There was no agreement between MRE and VMRE-predicted fibrosis stage (kappa = -0.01). The proportion of correctly predicted fibrosis stage was significantly higher for MRE compared to VMRE. MRE was significantly associated with fibrosis stage, but fat-corrected sADC was not (P = 0.24). DATA CONCLUSION: Fat-corrected VMRE was not associated with fibrosis stage in NAFLD. Further investigation is required if VMRE is to be considered in subjects with NAFLD. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

US LI-RADS Visualization Score: Interobserver Variability and Association With Cause of Liver Disease, Sex, and Body Mass Index.

OBJECTIVES: To evaluate the interobserver agreement between radiologists using the Ultrasound Liver Reporting And Data System (US LI-RADS) visualization score and assess association between visualization score and cause of liver disease, sex, and body mass index (BMI). METHODS: This retrospective, single institution, cross-sectional study evaluated 237 consecutive hepatocellular carcinoma surveillance US examinations between March 4, 2017 and September 4, 2017. Five abdominal radiologists independently assigned a US LI-RADS visualization score (A, no or minimal limitations; B, moderate limitations; C, severe limitations). Interobserver agreement was assessed with a weighted Kappa statistic. Association between US visualization score (A vs B or C) and cause of liver disease, sex, and BMI (< or ≥ 25 kg/m2) was evaluated using univariate and multivariate analyses. RESULTS: The average weighted Kappa statistic for all raters was 0.51. A score of either B or C was assigned by the majority of radiologists in 148/237 cases and was significantly associated with cause of liver disease (P = 0.014) and elevated BMI (P < 0.001). Subjects with viral liver disease were 3.32 times (95% CI: 1.44-8.38) more likely to have a score of A than those with non-alcoholic steatohepatitis (P = 0.007). The adjusted odds ratio of visualization score A was 0.249 (95% CI: 0.13-0.48) among those whose BMI was ≥25 kg/m2 vs. BMI < 25 kg/m2. CONCLUSION: Interobserver agreement between radiologists using US LI-RADS score was moderate. The majority of US examinations were scored as having moderate or severe limitations, and this was significantly associated with non-alcoholic steatohepatitis and increased BMI.

Toward individualized prediction of seizure recurrence: Hippocampal neuroimaging features in a cohort of patients from a first seizure clinic.

PURPOSE: We performed an exploratory analysis of electroencephalography (EEG) and neuroimaging data from a cohort of 51 patients with first seizure (FS) and new-onset epilepsy (NOE) to identify variables, or combinations of variables, that might discriminate between clinical trajectories over a one-year period and yield potential biomarkers of epileptogenesis. METHODS: Patients underwent EEG, hippocampal and whole brain structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS) within six weeks of the index seizure, and repeat neuroimaging one year later. We classified patients with FS as having had a single seizure (FS-SS) or having converted to epilepsy (FS-CON) after one year and performed logistic regression to identify combinations of variables that might discriminate between FS-SS and FS-CON, and between FS-SS and the combined group FS-CON + NOE. We performed paired t-tests to assess changes in quantitative variables over time. RESULTS: Several combinations of variables derived from hippocampal structural MRI, DTI, and MRS provided excellent discrimination between FS-SS and FS-CON in our sample, with areas under the receiver operating curve (AUROC) ranging from 0.924 to 1. They also provided excellent discrimination between FS-SS and the combined group FS-CON + NOE in our sample, with AUROC ranging from 0.902 to 1. After one year, hippocampal fractional anisotropy (FA) increased bilaterally, hippocampal radial diffusivity (RD) decreased on the side with the larger initial measurement, and whole brain axial diffusivity (AD) increased in patients with FS-SS; hippocampal volume decreased on the side with the larger initial measurement, hippocampal FA increased bilaterally, hippocampal RD decreased bilaterally and whole brain AD, FA and mean diffusivity increased in the combined group FS-CON + NOE (corrected threshold for significance, q = 0.017). CONCLUSION: We propose a prospective, multicenter study to develop and test models for the prediction of seizure recurrence in patients after a first seizure, based on hippocampal neuroimaging. Further longitudinal neuroimaging studies in patients with a first seizure and new-onset epilepsy may provide clues to the microstructural changes occurring at the earliest stages of epilepsy and yield biomarkers of epileptogenesis.

Assessing breast cancer risk within the general screening population: developing a breast cancer risk model to identify higher risk women at mammographic screening.

OBJECTIVES: To develop a breast cancer risk model to identify women at mammographic screening who are at higher risk of breast cancer within the general screening population. METHODS: This retrospective nested case-control study used data from a population-based breast screening program (2009-2015). All women aged 40-75 diagnosed with screen-detected or interval breast cancer (n = 1882) were frequency-matched 3:1 on age and screen-year with women without screen-detected breast cancer (n = 5888). Image-derived risk factors from the screening mammogram (percent mammographic density [PMD], breast volume, age) were combined with core biopsy history, first-degree family history, and other clinical risk factors in risk models. Model performance was assessed using the area under the receiver operating characteristic curve (AUC). Classifiers assigning women to low- versus high-risk deciles were derived from risk models. Agreement between classifiers was assessed using a weighted kappa. RESULTS: The AUC was 0.597 for a risk model including only image-derived risk factors. The successive addition of core biopsy and family history significantly improved performance (AUC = 0.660, p < 0.001 and AUC = 0.664, p = 0.04, respectively). Adding the three remaining risk factors did not further improve performance (AUC = 0.665, p = 0.45). There was almost perfect agreement (kappa = 0.97) between risk assessments based on a classifier derived from image-derived risk factors, core biopsy, and family history compared with those derived from a model including all available risk factors. CONCLUSIONS: Women in the general screening population can be risk-stratified at time of screen using a simple model based on age, PMD, breast volume, and biopsy and family history. KEY POINTS: • A breast cancer risk model based on three image-derived risk factors as well as core biopsy and first-degree family history can provide current risk estimates at time of screen. • Risk estimates generated from a combination of image-derived risk factors, core biopsy history, and first-degree family history may be more valid than risk estimates that rely on extensive self-reported risk factors. • A simple breast cancer risk model can avoid extensive clinical risk factor data collection.

Ultrasound and CT in the Diagnosis of Appendicitis: Accuracy With Consideration of Indeterminate Examinations According to STARD Guidelines.

OBJECTIVE. The objective of our study was to determine the accuracy of ultrasound (US) and CT in diagnosing appendicitis at our institution while taking into account the number of indeterminate examinations in accordance with the Standards for Reporting Diagnostic Accuracy (STARD) guidelines. MATERIALS AND METHODS. We retrospectively evaluated 790 patients who underwent US, CT, or both for evaluation of suspected appendicitis between May 1, 2013, and April 30, 2015. Patient characteristics and US and CT examination results were recorded. The reference standard was histopathology or 3 months of medical record follow-up if surgery was not performed; 3 × 2 tables were generated, and sensitivity, specificity, overall test yield, and accuracy were calculated according to STARD guidelines. For surgical cases, time to surgery (one-way ANOVA) was compared among patients who underwent US alone, CT alone, or both US and CT. RESULTS. A total of 473 of 562 US examinations had indeterminate findings (overall test yield, 15.8%); sensitivity and specificity in the 89 diagnostic examinations were 98.5% and 54.2%, respectively. Thirteen of 522 CT examinations were indeterminate (overall test yield, 97.5%); sensitivity and specificity in the remaining 509 CT examinations were 98.9% and 97.2%, respectively. Taking indeterminate studies into account, the accuracy was 13.7% for US and 95.6% for CT. The negative appendectomy rates were 17.7% (11/62) for US and 3.3% (9/276) for CT (p = 0.0002). Time to surgery was longer for patients who underwent US and CT (mean ± SD, 17.7 ± 8.9 hours) than US alone (12.9 ± 6.4 hours; p = 0.002) but was not longer for patients who underwent CT alone (16.3 ± 8.4 hours; p = 0.45). CONCLUSION. At our institution, a large proportion of US examinations are indeterminate for appendicitis. CT is the preferred first-line imaging test for evaluating appendicitis in nonobstetric adult patients.

Maternal pre-pregnancy obesity and health care utilization and costs in the offspring.

BACKGROUND/OBJECTIVE: The association between maternal pre-pregnancy obesity and adverse child health outcomes is well described, but there are few data on the relationship with offspring health service use. We examined the influence of maternal pre-pregnancy obesity on offspring health care utilization and costs over the first 18 years of life. METHODS: This was a population-based retrospective cohort study of children (n = 35,090) born between 1989 and 1993 and their mothers, who were identified using the Nova Scotia Atlee Perinatal Database and linked to provincial administrative health data from birth through 2014. The primary outcome was health care utilization as determined by the number and cost of physician visits, hospital admissions and days, and high utilizer status (>95th percentile of physician visits). The secondary outcome was health care utilization by ICD chapter. Maternal pre-pregnancy weight was categorized as normal weight, overweight, or obese. Multivariable-adjusted regression models were used to examine the association between maternal weight status and offspring health care use. RESULTS: Children of mothers with pre-pregnancy obesity had more physician visits (10%), hospital admissions (16%), and hospital days (10%) than children from mothers of normal weight over the first 18 years of life. Offspring of mothers with obesity had C$356 higher physician costs and C$1415 hospital costs over 18 years than offspring of normal weight mothers. Children of mothers with obesity were 1.74 times more likely to be a high utilizer of health care and had higher rates of physician visits and hospital stays for nervous system and sense organ disorders, respiratory disorders, and gastrointestinal disorders compared to children of normal weight mothers. CONCLUSION: Our findings suggest that maternal pre-pregnancy overweight and obesity are associated with slightly higher offspring health care utilization and costs in the first 18 years of life.

How Do Different Indices of Hepatic Enhancement With Gadoxetic Acid Compare in Predicting Liver Failure and Other Major Complications After Hepatectomy?

OBJECTIVE: The objective of this study was to assess the accuracy of gadoxetic acid hepatic enhancement indices in predicting posthepatectomy liver failure (PHLF) and other major complications (OMCs). METHODS: Sixty-five patients underwent prehepatectomy gadoxetic acid-enhanced magnetic resonance imaging. Enhancement indices were calculated by obtaining regions of interest on magnetic resonance images and segmented volumes of the liver and spleen. Multivariate regression analysis was performed to predict PHLF and OMC as a function of the indices, and areas under the receiver operator characteristic (AUROC) curves were calculated. RESULTS: Areas under the receiver operator characteristic values varied from 0.412 to 0.681 and 0.462 to 0.738 in predicting PHLF and OMC, respectively. The most accurate indices in predicting PHLF were the region of interest-based, fat-normalized relative liver enhancement and liver enhancement index (AUROC, 0.681). The most accurate index in predicting OMC was the volumetric least-squares regression slope of a pharmacokinetic model (Khep_V, AUROC, 0.738). CONCLUSIONS: Indices of gadoxetic acid liver enhancement demonstrate variable performance in predicting PHLF and OMC.

Diagnostic Reference Levels and Monitoring Practice Can Help Reduce Patient Dose From CT Examinations.

OBJECTIVE: The purpose of this study is to establish provincial diagnostic reference levels (DRLs) and to determine whether this process may help reduce the patient radiation dose from the most frequently performed CT examinations. MATERIALS AND METHODS: We investigated the following CT examinations: head, chest, low-dose chest, abdomen and pelvis, and chest, abdomen, and pelvis examinations. The sample for each protocol included 15 patients of average body weight (mean [± SD], 70 ± 20 kg). The differences in dose between scanners were evaluated using one-way ANOVA. Correlations between dose, scanner age, and the number of detector rows were assessed using the Pearson correlation coefficient. A sample of abdominal and chest examinations were randomized and blinded for review by experienced radiologists who graded diagnostic image quality. Provincial DRLs were calculated as the 75th percentile of patient dose distributions. For hospitals with doses exceeding the DRLs, dose reduction was recommended, followed by another survey. RESULTS: The initial survey included data of 1185 patients, and an additional 180 patients were surveyed after protocol optimization. The differences between the mean values of the dose distributions from each scanner were statistically significant (p < 0.05) for all examinations. The variation was greatest for low-dose chest CT, with a greater than fivefold difference in the mean dose values noted between scanners. A very weak correlation was found between dose and scanner age or the number of detector rows. Analysis of image quality revealed no statistically significant differences in any scoring categories, with the exception of the noise category in abdominal imaging. Implementation of the DRLs allowed a reduction in patient dose of up to 41% as a result of a protocol change. CONCLUSION: Establishing provincial DRLs allows an effective reduction in patient dose without resulting in degradation of image quality.

Predicting EGFR mutation status in lung cancer:Proposal for a scoring model using imaging and demographic characteristics.

OBJECTIVE: To determine if a combination of CT and demographic features can predict EGFR mutation status in bronchogenic carcinoma. METHODS: We reviewed demographic and CT features for patients with molecular profiling for resected non-small cell lung carcinoma. Using multivariate logistic regression, we identified features predictive of EGFR mutation. Prognostic factors identified from the logistic regression model were then used to build a more practical scoring system. RESULTS: A scoring system awarding 5 points for no or minimal smoking history, 3 points for tumours with ground glass component, 3 points for airbronchograms, 2 points for absence of preoperative evidence of nodal enlargement or metastases and 1 point for doubling time of more than a year, resulted in an AUROC of 0.861. A total score of at least 8 yielded a specificity of 95 %. On multivariate analysis sex was not found to be predictor of EGFR status. CONCLUSIONS: A weighted scoring system combining imaging and demographic data holds promise as a predictor of EGFR status. Further studies are necessary to determine reproducibility in other patient groups. A predictive score may help determine which patients would benefit from molecular profiling and may help inform treatment decisions when molecular profiling is not possible. KEY POINTS: • EGFR mutation-targeted chemotherapy for bronchogenic carcinoma has a high success rate. • Mutation testing is not possible in all patients. • EGFR associations include subsolid density, slow tumour growth and minimal/no smoking history. • Demographic or imaging features alone are weak predictors of EGFR status. • A scoring system, using imaging and demographic features, is more predictive.

Patterns of health care utilization preceding a colorectal cancer diagnosis are strong predictors of dying quickly following diagnosis.

BACKGROUND: Understanding the predictors of a quick death following diagnosis may improve timely access to palliative care. The objective of this study was to explore whether factors in the 24 months prior to a colorectal cancer (CRC) diagnosis predict a quick death post-diagnosis. METHODS: Data were from a longitudinal study of all adult persons diagnosed with CRC in Nova Scotia, Canada, from 01Jan2001-31Dec2005. This study included all persons who died of any cause by 31Dec2010, except those who died within 30 days of CRC surgery (n = 1885 decedents). Classification and regression tree models were used to explore predictors of time from diagnosis to death for the following time intervals: 2, 4, 6, 8, 12, and 26 weeks from diagnosis to death. All models were performed with and without stage at diagnosis as a predictor variable. Clinico-demographic and health service utilization data in the 24 months pre-diagnosis were provided via linked administrative databases. RESULTS: The strongest, most consistent predictors of dying within 2, 4, 6, and 8 weeks of CRC diagnosis were related to health services utilization in the 24 months prior to diagnosis: i.e., number of specialist visits, number of days spent in hospital, and number of family physician visits. Stage at diagnosis was the strongest predictor of dying within 12 and 26 weeks of diagnosis. CONCLUSIONS: Identifying potential predictors of a short timeframe between cancer diagnosis and death may aid in the development of strategies to facilitate timely and appropriate referral to palliative care upon a cancer diagnosis.

A classification tree for the prediction of benign versus malignant disease in patients with small renal masses.

INTRODUCTION: To develop a classification tree for the preoperative prediction of benign versus malignant disease in patients with small renal masses. MATERIALS AND METHODS: This is a retrospective study including 395 consecutive patients who underwent surgical treatment for a renal mass < 5 cm in maximum diameter between July 1st 2001 and June 30th 2010. A classification tree to predict the risk of having a benign renal mass preoperatively was developed using recursive partitioning analysis for repeated measures outcomes. Age, sex, volume on preoperative imaging, tumor location (central/peripheral), degree of endophytic component (1%-100%), and tumor axis position were used as potential predictors to develop the model. RESULTS: Forty-five patients (11.4%) were found to have a benign mass postoperatively. A classification tree has been developed which can predict the risk of benign disease with an accuracy of 88.9% (95% CI: 85.3 to 91.8). The significant prognostic factors in the classification tree are tumor volume, degree of endophytic component and symptoms at diagnosis. As an example of its utilization, a renal mass with a volume of < 5.67 cm3 that is < 45% endophytic has a 52.6% chance of having benign pathology. Conversely, a renal mass with a volume ≥ 5.67 cm3 that is ≥ 35% endophytic has only a 5.3% possibility of being benign. CONCLUSIONS: A classification tree to predict the risk of benign disease in small renal masses has been developed to aid the clinician when deciding on treatment strategies for small renal masses.

Cone-beam CT: an additional imaging tool in the interventional treatment and management of low-flow vascular malformations.

PURPOSE: To evaluate the impact of cone-beam computed tomography (CT) during sclerotherapy of low-flow vascular malformations. MATERIALS AND METHODS: Eighty-seven cone-beam CT examinations were acquired during 81 sclerotherapy treatments of low-flow malformations in 48 patients: 81 were performed to evaluate sclerosing agent diffusion and six were performed to evaluate needle or catheter positioning before injection of therapeutic agent. Image quality was rated by two observers. Clinical impact of cone-beam CT in the assessment of therapeutic agent diffusion, needle or catheter positioning, subsequent treatment planning, and complication detection was evaluated. The κ-statistic was used to assess interobserver reliability and proportions, with associated 95% confidence intervals (CIs). RESULTS: All cone-beam CT images were successfully acquired. Image quality was rated as excellent or good for the majority of studies, with substantial interobserver reliability (κ = 0.648). Cone-beam CT studies improved assessment of therapeutic agent diffusion in 83% of cases (67 of 81; 95% CI, 75%-91%) for observer 1, who had access to ultrasound, fluoroscopic, and digital subtraction angiographic (DSA) imaging, and in 95% of cases (77 of 81; 95% CI, 90%-100%) for observer 2, who had access to only stored fluoroscopic spot radiographs and DSA images. Cone-beam CT impacted planning of the next treatment session in 49% of cases (40 of 81; 95% CI, 38%-60%). In 7% of cases (six of 81; 95% CI, 1%-13%), complications such as migration of therapeutic agent or compression of upper airways were detected that were not seen with other imaging. CONCLUSIONS: Cone-beam CT can be a useful adjunctive imaging tool, providing information to help decision-making during percutaneous sclerotherapy and ongoing management of low-flow vascular malformations.

Quality of life and survival analysis of patients undergoing transarterial chemoembolization for primary hepatic malignancies: a prospective cohort study.

INTRODUCTION: Transarterial chemoembolization (TACE) is indicated for primary hepatic tumours when resection or local ablation are not feasible. Patients undergoing TACE have a better survival than best supportive therapy. However, there is paucity of prospective studies on the quality of life (QOL) after TACE for primary hepatic malignancies, especially in the Western world. PURPOSE: The primary aim of the present study was to determine if TACE impacts on the QOL of patients affected by primary hepatic tumours, and to assess treatment efficacy in a prospective cohort of patients treated at a tertiary Canadian university medical centre. METHODS: From September 2005 to December 2010, 48 candidates for TACE underwent at least one TACE session. Data on their QOL, tumour response, serum alpha fetoprotein (AFP) and survival were prospectively collected every 3-4 months. RESULTS: The overall QOL of patients undergoing TACE did not decline during the first 12 months after treatment. A decline was observed in the physical health domain after the third TACE that coincided with the increasing size of the largest tumour and a rise in the serum AFP levels. Psychological, social and environmental domains remained stable throughout the treatment period. Multivariate analysis revealed that tumour focality, AFP levels and model of end-stage liver disease (MELD) scores were associated with long-term survival (P= 0.001, P= 0.01, P= 0.02, respectively). The overall survival at 12, 36 and 48 months were 72%, 28% and 12%, respectively. CONCLUSION: TACE is an effective palliative intervention for unresectable and non-ablatable primary liver tumours without affecting the QOL of patients even when repeated interventions are performed.

Analysis of survival predictors in a prospective cohort of patients undergoing transarterial chemoembolization for hepatocellular carcinoma in a single Canadian centre.

BACKGROUND: Despite advances in the treatment of hepatocellular carcinoma (HCC), a great proportion of patients are eligible only for palliative therapy for reasons of advanced-stage disease or poor hepatic reserve. The use of transarterial chemoembolization (TACE) in the palliation of non-resectable HCC has shown a survival benefit in European and Asian populations. The aim of this study was to assess the efficacy of TACE by analysing overall 5-year survival, interval changes of tumour size and serum alpha-fetoprotein (AFP) levels in a prospective North American cohort. METHODS: From September 2005 to December 2010, 46 candidates for TACE were enrolled in the study. Collectively, they underwent 102 TACE treatments. Data on tumour response, serum AFP and survival were prospectively collected. RESULTS: In compensated cirrhotic patients, serial treatment with TACE had a stabilizing effect on tumour size and reduced serum AFP levels during the first 12 months. Overall survival rates at 1, 2 and 3 years were 69%, 58% and 20%, respectively. Younger individuals and patients with a lower body mass index, affected by early-stage HCC with involvement of a single lobe, had better survival in univariate analysis. After adjustment for risk factors, early tumour stage (T1 and T2 vs. T3 and T4) at diagnosis was the only statistically significant predictor for survival. CONCLUSIONS: In compensated cirrhotic patients, TACE is an effective palliative intervention and HCC stage at diagnosis seems to be the most important predictor of longterm outcomes.

Transabdominal ultrasound of pancreatic ductal adenocarcinoma: A multi-centered population-based study in sensitivity, associated diagnostic intervals, and survival.

OBJECTIVES: To determine the sensitivity of ultrasound (US) in detecting pancreatic ductal adenocarcinoma in our region, to identify factors associated with US test result, and assess the impact on the diagnostic interval and survival. METHODS: Patients diagnosed between January 1, 2014 and December 31, 2015 in Nova Scotia, Canada were identified by a cancer registry. US performed prior to diagnosis were retrospectively graded as true positive (TP), indeterminate or false negative (FN). Amongst US results, differences in age, weight and tumor size were assessed [one-way analysis of variance (ANOVA)]. Associations between result and sex, tumor location (proximal/distal), clinical suspicion of malignancy, and visualization of the pancreas, tumor, secondary signs and liver metastases were assessed (Chi-square). Mean follow-up imaging, diagnostic, and survival intervals were assessed (one-way ANOVA). RESULTS: One hundred thirteen US of 107 patients (54 women; mean 70 ± 13 years) were graded as follows: 48/113 (42.5%) TPs; 42/113 (37.2%) indeterminates; and 23/113 (20.4%) FNs. Sensitivity was 48/71(67.6%). There was no difference in age, weight or tumor size amongst US result (P > 0.5). FNs had proportionally more men (P = 0.011) and lacked clinical suspicion of malignancy (P = 0.0006); TPs had proportionally more proximal tumors (P = 0.017). US result was associated with visualization of the pancreas, tumor, secondary signs and liver metastases (P < 0.005). FNs had longer mean follow-up imaging (P < 0.0001) and diagnostic (P = 0.0007) intervals, and worse mean survival (P = 0.034). CONCLUSIONS: In our region, the sensitivity of US in detecting pancreatic ductal adenocarcinoma is 67.6%. A false negative US is associated with delayed diagnostic work-up and worse mean survival.

Immunohistochemical expression and prognostic value of ER, PR and HER2/neu in pancreatic and small intestinal neuroendocrine tumors.

BACKGROUND AND AIMS: There has been limited study of estrogen and progesterone receptor (ER/PR) expression in gastrointestinal neuroendocrine tumors (GINETs) despite emerging evidence of hormone receptor regulation of pancreatic islet cells. Beta cells express PR and progesterone has been implicated in the pathogenesis of gestational diabetes. There is conflicting information regarding HER2/neu protein overexpression in GINETs. Investigation of ER, PR and HER2/neu expression in GINETs is therefore warranted. METHODS: A pathology database search identified 77 patients with primary pancreatic (40) or small intestinal (37) NETs diagnosed from 1991 to 2009. Ki67, ER, PR and HER2/neu were assessed via immunohistochemistry. ER and PR were interpreted as negative (0), 1+ (Allred score 3-7/8) or 2+ (Allred score 8/8), and HER2/neu was assessed according to ASCO/CAP guidelines for breast carcinoma. Clinical correlation and survival outcomes were ascertained by a retrospective clinical chart review. RESULTS: 2+ PR staining was observed more often in pancreatic compared to small intestinal cases (55 vs. 8%; p < 0.001). All small intestinal NETs with 2+ PR were duodenal primaries. Cases with 2+ PR presented significantly less often with nodal or distant metastases compared to cases with 0/1+ PR (13 vs. 61.5%; p < 0.001) and had significantly improved disease-free survival (median 155 vs. 38 months; p = 0.037). Only one case demonstrated 2+ ER staining and all were negative for HER2/neu. CONCLUSION: GINETs with strong (2+) PR expression are associated with pancreatic/duodenal origin, lower stage disease, and more favorable clinical prognosis. Further study is needed to determine the clinical utility of PR expression in GINETs.

Clinical epidemiological analysis of the mortality rate of liver transplant candidates living in rural areas.

MELD score has been used to predict 90-day mortality of subjects listed for liver transplantation (OLT). Validation of MELD score for patients on the waiting list in transplant programmes serving rural areas in North America is lacking. A retrospective cohort of patients affected by end-stage liver disease was studied to assess the mortality rate within 90 days after being listed at our transplant centre. Secondary aims were to identify differences between predicted and observed 90-days mortality using MELD and MELDNa scores at the time of listing. Among 126 patients included in this study, waiting list mortality was 35.0%. Ninety-day mortality was 21.1%, which was significantly greater than the mortality estimated by the MELD (9.1%, 95% CI: 6.6-11.5) and MELDNa (9.3%, 95%CI: 6.0-12.5). Despite this underestimation, AUC for MELD and MELDNa was 0.80 and 0.78 respectively. In our study, independent predictors of waiting list mortality were age, diagnosis of cholestatic disease and residence over 500 km from our transplant centre. MELD and MELDNa underestimated the 90-day mortality in patients with liver failure living in rural areas. Validation of these models should be performed in other transplant centres serving patients with limited access to specialized services.

Do family physicians request ultrasound scans appropriately?

OBJECTIVE: To review family physicians' requests for abdominal, thyroid, pelvic, soft tissue, and carotid ultrasound (US) scans, and to determine whether 5% or more of these tests were not clearly indicated based on the clinical history provided. DESIGN: Analysis of 620 randomly chosen requests for US scans. SETTING: The Radiology Department at the Capital District Health Authority in Halifax, NS, between October 1, 2008, and June 30, 2009. PARTICIPANTS: Two radiologists and 2 family physicians with clinical expertise and familiarity with the Canadian Association of Radiologists' 2005 guidelines. MAIN OUTCOME MEASURES: Whether US requests were "indicated," "not clearly indicated," or "not legible" according to the Canadian Association of Radiologists' 2005 guidelines. Those that were illegible were discarded and replaced. Results More than 5% of requests for abdominal, thyroid, or carotid US scans were not clearly indicated. The percentages of requests for pelvic and soft tissue scans that were not clearly indicated were not significant. The reviewers found only 5 illegible request forms. Percentages of abdominal, thyroid, and carotid US scans not clearly indicated were 12.1%, 18.8%, and 25.2%, respectively. Reasons for inappropriate US requests included the following: wrong tests (3.2%), vague clinical questions (4.8%), and unfocused examinations (4.8%) for abdominal scans; wrong tests (3.2%), vague clinical questions (3.2%), unnecessary investigations (5.6%), and unnecessary follow-up examinations (5.6%) for thyroid scans; and unnecessary tests (10.5%), vague clinical questions (5.6%), and unnecessary tests for "dizziness" (10.5%) for carotid scans. CONCLUSION: More than 5% of the abdominal, thyroid, and carotid US scans requested by family physicians were not clearly indicated based on the clinical history provided. Common trends in requesting these examinations reinforce the need to improve guidelines for requesting scans and for managing many presenting complaints in family practice.

Diagnostic performance of US for suspected appendicitis: Does multi-categorical reporting provide better estimates of disease in adults, and what factors are associated with false or indeterminate results?

PURPOSE: To identify factors associated with false or indeterminate US result for suspected appendicitis, and assess whether multi-categorical reporting of US yields more precise estimates regarding the probability of appendicitis. METHODS: 562 US examinations for suspected appendicitis between May 2013-April 2015 were categorized as true (77/562 true positives or true negatives) or false/indeterminate (485/562 false negatives, false positives or indeterminates) based on results from a prior study. Of 541 examinations with images available retrospectively, a category of A-E was assigned as follows: non-visualized appendix with secondary findings (A) absent or (B) present; appendix visualized and considered (C) negative, (D) equivocal, or (E) positive for appendicitis. The following factors were recorded: age; sex; scan time (daytime vs. off-hours); resident/fellow involvement; abdominal subspecialty radiologist; radiologist experience (>5 years or not); and tenderness on interrogation. Associations between factors and US result were assessed (t-tests, Fisher's exact test and multivariate logistic regression). RESULTS: The true group had proportionally more males (18/77 (23.4%) vs. 66/485 (13.6%), p = 0.04) and patients with sonographic tenderness (43/77 (55.8%) vs. 132/353 (27.3%), p < 0.0001). There was no significant difference or association with other factors. On multivariate logistic regression, false/indeterminate results were 1.9 times (95% CIs 1.0-3.5) more likely among females and 3.8 times more likely in the absence of tenderness (95% CIs 2.3-6.4). The proportion of patients with appendicitis in categories A-E was 34/410 (8.3%), 24/44 (54.5%), 0/18 (0%), 0/3 (0%) and 61/66 (92.4%), respectively. CONCLUSIONS: Females and absence of tenderness were associated with a false/indeterminate US. Categorical reporting provides more granular estimates of the post-test probability of appendicitis.