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Conventional cross-sectional imaging done shortly after radioembolization of hepatocellular carcinoma (HCC) does not reliably predict long-term response to treatment. This study evaluated whether quantitative contrast-enhanced ultrasound (CEUS) can predict the long-term response of HCC to yttrium-90 (Y-90) treatment. Fifteen patients underwent CEUS at three time points: immediately following treatment and 1 and 2 wk post-treatment. Response 3–6 mo after treatment was categorized on contrast-enhanced magnetic resonance imaging by two experienced radiologists using the Modified Response Evaluation Criteria in Solid Tumors. CEUS data were analyzed by quantifying tumor perfusion and residual fractional vascularity using time–intensity curves. Patients with stable disease on magnetic resonance imaging had significantly greater fractional vascularity 2 wk post-treatment (65.15%) than those with partial or complete response (13.8 ± 9.9%, p = 0.007, and 14.9 ± 15.4%, p = 0.009, respectively). Complete responders had lower tumor vascularity at 2 wk than at post-operative examination (–38.3 ± 15.4%, p = 0.045). Thus, this pilot study suggests CEUS may provide an earlier indication of Y-90 treatment response than cross-sectional imaging.

BACKGROUND: US contrast agents are gas-filled microbubbles (MBs) that can be locally destroyed by using external US. Among other bioeffects, US-triggered MB destruction, also known as UTMD, has been shown to sensitize solid tumors to radiation in preclinical models through localized insult to the vascular endothelial cells. PURPOSE: To evaluate the safety and preliminary efficacy of combining US-triggered MB destruction and transarterial radioembolization (TARE) in participants with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In this pilot clinical trial, participants with HCC scheduled for sublobar TARE were randomized to undergo either TARE or TARE with US-triggered MB destruction 1–4 hours and approximately 1 and 2 weeks after TARE. Enrollment took place between July 2017 and February 2020. Safety of US-triggered MB destruction was evaluated by physiologic monitoring, changes in liver function tests, adverse events, and radiopharmaceutical distribution. Treatment efficacy was evaluated by using modified Response Evaluation Criteria in Solid Tumors (mRECIST) on cross-sectional images, time to required next treatment, transplant rates, and overall survival. Differences across mRECIST reads were compared by using a Mann-Whitney U test, and the difference in prevalence of tumor response was evaluated by Fisher exact test, whereas differences in time to required next treatment and overall survival curves were compared by using a log-rank (Mantel-Cox) test. RESULTS: Safety results from 28 participants (mean age, 70 years ± 10 [standard deviation]; 17 men) demonstrated no significant changes in temperature (P = .31), heart rate (P = .92), diastolic pressure (P = .31), or systolic pressure (P = .06) before and after US-triggered MB destruction. No changes in liver function tests between treatment arms were observed 1 month after TARE (P > .15). Preliminary efficacy results showed a greater prevalence of tumor response (14 of 15 [93%; 95% CI: 68, 100] vs five of 10 [50%; 95% CI: 19, 81]; P = .02) in participants who underwent both US-triggered MB destruction and TARE (P = .02). CONCLUSION: The combination of US-triggered microbubble destruction and transarterial radioembolization is feasible with an excellent safety profile in this patient population and appears to result in improved hepatocellular carcinoma treatment response. © RSNA, 2020

Prior work has shown that microbubble-assisted delivery of oxygen improves tumor oxygenation and radiosensitivity, albeit over a limited duration. Lonidamine (LND) has been investigated because of its ability to stimulate glycolysis, lactate production, inhibit mitochondrial respiration, and inhibit oxygen consumption rates in tumors but suffers from poor bioavailability. The goal of this work was to characterize LND-loaded oxygen microbubbles and assess their ability to oxygenate a human head and neck squamous cell carcinoma (HNSCC) tumor model, while also assessing LND biodistribution. In tumors treated with surfactant-shelled microbubbles with oxygen core (SE61O(2)) and ultrasound, pO(2) levels increased to a peak 19.5 ± 9.7 mmHg, 50 s after injection and returning to baseline after 120 s. In comparison, in tumors treated with SE61O(2)/LND and ultrasound, pO(2) levels showed a peak increase of 29.0 ± 8.3 mmHg, which was achieved 70 s after injection returning to baseline after 300 s (p < 0.001). The co-delivery of O(2) and LND via SE61 also showed an improvement of LND biodistribution in both plasma and tumor tissues (p < 0.001). In summary, ultrasound-sensitive microbubbles loaded with O(2) and LND provided prolonged oxygenation relative to oxygenated microbubbles alone, as well as provided an ability to locally deliver LND, making them more appropriate for clinical translation.

Much of the volume of solid tumors typically exists in a chronically hypoxic microenvironment that has been shown to result in both chemotherapy and radiation therapy resistance. The purpose of this study was to use localized microbubble delivery to overcome hypoxia prior to therapy.In this study, surfactant-shelled oxygen microbubbles were fabricated and injected intravenously to locally elevate tumor oxygen levels when triggered by noninvasive ultrasound in mice with human breast cancer tumors. Changes in oxygen and sensitivity to radiation therapy were then measured.In this work, we show that oxygen-filled microbubbles successfully and consistently increase breast tumor oxygenation levels in a murine model by 20 mmHg, significantly more than control injections of saline solution or untriggered oxygen microbubbles (P .001). Using photoacoustic imaging, we also show that oxygen delivery is independent of hemoglobin transport, enabling oxygen delivery to avascular regions of the tumor. Finally, we show that overcoming hypoxia by this method immediately prior to radiation therapy nearly triples radiosensitivity. This improvement in radiosensitivity results in roughly 30 days of improved tumor control, providing statistically significant improvements in tumor growth and animal survival (P .03).Our findings demonstrate the potential advantages of ultrasound-triggered oxygen delivery to solid tumors and warrant future efforts into clinical translation of the microbubble platform.

Author(s): Chirikova, Ekaterina; Cahoon, Elizabeth K; Rozhko, Alexander; Drozdovitch, Vladimir; Little, Mark P; McConnell, Robert J; Minenko, Victor; Veyalkin, Ilya; Yauseyenka, Vasilina; Hatch, Maureen; O’Kane, Patrick; Zablotska, Lydia B | Abstract: Abstract Thyroid enlargement can cause problems with swallowing or breathing and a decrease in accuracy of screening for thyroid cancer. Exposure to radioactive iodines after the 1986 Chernobyl accident is known to increase risk of thyroid cancer in those exposed at a young age, but little is known about its effects on thyroid volume, which could have important clinical implications. The objective of this study is to characterize the dose-response association between iodine-131 (131I) exposure and thyroid volume using data from a Belarusian-American cohort study of residents of Belarus exposed during childhood. Persons exposed to Chernobyl fallout in Belarus at the age of 18 years or younger had individual 131I doses to the thyroid gland estimated from direct thyroid activity measurements, radioecological and biokinetic models, and interview data on whereabouts and dietary habits collected during baseline screening in 1996-2001 (N=11,970; median age 21 years). Thyroid volume was estimated from thyroid ultrasound measurements during screening. Individuals with diagnoses of benign or malignant tumors of thyroid gland, any thyroid surgery or aplasia, and missing thyroid volume measurements were excluded (n=1,104). Dose and thyroid volume were log-transformed due to right-skewed distributions. We used a multivariable linear regression to estimate the dose-response association between 131I dose to the thyroid and thyroid volume accounting for confounding effects of sex, age at screening, and place of residence at the time of screening, a proxy for endemic iodine deficiency. To examine nonlinear effects, we added a quadratic term for the log-transformed dose. Among 10,866 participants, dose to thyroid ranged from 0.0005 to 39 gray (Gy) (median=0.3 Gy). In a linear regression model adjusted for confounders, log thyroid volume was best described by a linear-quadratic function of log dose (pl0.001 for log dose and log dose-squared coefficients). The largest effect was observed for doses 0.3-0.6 Gy (14%), then gradually decreased. Subjects with thyroid dose of 1 Gy had an average thyroid volume 13.6% (95% CI 8- 19.2%) higher compared to those with dose 1 mGy. Thyroid volume increased with age and was significantly higher for males compared to females and for those from Minsk city and area compared to other regions (both pl0.001). The adjusted R2-value was 30%, suggesting unaccounted factors that might better explain this association. This is the first study to assess the dose-response association between exposure to 131I and thyroid volume. Although statistically significant, the observed increase in thyroid volume with dose was small. Availability of measurements of iodine deficiency and dietary habits around the time of an accident in the future studies of nuclear accidents will be essential for understanding the mechanism of association between radiation dose and thyroid volume in young people.

Objectives To use subharmonic imaging (SHI) to depict the vascularity of pancreatic masses compared to contrast-enhanced endoscopic ultrasound (EUS) and pathologic results. Methods Sixteen patients scheduled for biopsy of a pancreatic mass were enrolled in an Institutional Review Board–approved study. Pulse-inversion SHI (transmitting/receiving at 2.5/1.25 MHz) was performed on a LOGIQ 9 system (GE Healthcare, Milwaukee, WI) with a 4C transducer, whereas contrast harmonic EUS (transmitting/receiving at 4.7/9.4 MHz) was performed with a radial endoscope (GF-UTC180; Olympus Corporation, Tokyo, Japan) connected to a ProSound SSD α-10 scanner (Hitachi Aloka, Tokyo, Japan). Two injections of the contrast agent Definity (Lantheus Medical Imaging, North Billerica, MA) were administrated (0.3–0.4 and 0.6–0.8 mL for EUS and SHI, respectively). Contrast-to-tissue ratios (CTRs) in the mass and an adjacent vessel were calculated. Four physicians independently scored the images (benign to malignant) for diagnostic accuracy and inter-reader agreement. Results One patient dropped out before imaging, leaving 11 adenocarcinomas, 1 gastrointestinal stromal tumor with pancreatic infiltration, and 3 benign masses. Marked subharmonic signals were obtained in all patients, with intratumoral blood flow clearly visualized with SHI. Significantly greater CTRs were obtained in the masses with SHI than with EUS (mean ± SD, 1.71 ± 1.63 versus 0.63 ± 0.89; P = .016). There were no differences in the CTR in the surrounding vessels or when grouped by pathologic results (P > .60). The accuracies for contrast EUS and SHI were low (

OBJECTIVES—: Hypoxic cancer cells have been shown to be more resistant to radiation therapy than normoxic cells. Hence, this study investigated whether ultrasound (US)-induced rupture of oxygen-carrying microbubbles (MBs) would enhance the response of breast cancer metastases to radiation. METHODS—: Nude mice (n = 15) received stereotactic injections of brain-seeking MDA-MB-231 breast cancer cells into the right hemisphere. Animals were randomly assigned into 1 of 5 treatment groups: no intervention, 10 Gy radiation using a small-animal radiation research platform, nitrogen-carrying MBs combined with US-mediated MB rupture immediately before 10 Gy radiation, oxygen-carrying MBs immediately before 10 Gy radiation, and oxygen-carrying MBs with US-mediated MB rupture immediately before 10 Gy radiation. Tumor progression was monitored with 3-dimensional US, and overall survival was noted. RESULTS—: All groups except those treated with oxygen-carrying MB rupture and radiation had continued rapid tumor growth after treatment. Tumors treated with radiation alone showed a mean increase in volume ± SD of 337% ± 214% during the week after treatment. Tumors treated with oxygen-carrying MBs and radiation without MB rupture showed an increase in volume of 383% ± 226%. Tumors treated with radiation immediately after rupture of oxygen-carrying MBs showed an increase in volume of only 41% ± 1% (P = 0.045), and this group also showed a 1 week increase in survival time. CONCLUSIONS—: Adding US-ruptured oxygen-carrying MBs to radiation therapy appears to delay tumor progression and improve survival in a murine model of metastatic breast cancer.

Objective: This study evaluated the performance of automated machine-learning to diagnose non-alcoholic fatty liver disease (NAFLD) by ultrasound and compared these findings to radiologist performance.Methods: 96 patients with histologic (33) or proton density fat fraction MRI (63) diagnosis of NAFLD and 100 patients without evidence of NAFLD were retrospectively identified. The “Fatty Liver” label included 96 patients with 405 images and the “Not Fatty Liver” label included 100 patients with 500 images. These 905 images made up a “Comprehensive Image” group. A “Radiology Selected Image” group was then created by selecting only images considered diagnostic by a blinded radiologist, resulting in 649 images. Cloud AutoML Visionbeta (Google LLC, Mountain View, CA) was used for machine learning. The models were evaluated against three blinded radiologists.Results: The “Comprehensive Image” group model demonstrated a sensitivity of 88.6% (73.3-96.8%) and a specificity of 95.3% (84.2-99.4%). Radiologist performance on this image group included a sensitivity of 81.0% (74.3-87.6%) and specificity of 86.0% (72.6-99.5%). The model’s overall accuracy was 92.3% (84.0-97.1%), compared with mean individual performance (83.8%, 78.4-89.1%). The “Radiology Selected Image” group model demonstrated a sensitivity of 88.6% (73.3 - 96.8%) and specificity of 87.9% (71.8-96.6%). Mean radiologist sensitivity was 92.4% (86.9-97.9%) and specificity was 91.9% (83.4-100%). The model’s overall accuracy was 88.2% (78.1-94.8%) which was comparable to the individual radiologist performance (92.2%, 90.1-94.2%) and consensus performance (95.6%, 87.6-99.1%).Conclusions: An automated machine-learning algorithm may accurately detect NAFLD on ultrasound.

OBJECTIVES To assess the performance of molecular lymphosonography with dual-targeted microbubbles in detecting and quantifying the metastatic involvement in sentinel lymph nodes (SLNs) using a swine melanoma model. METHODS Targeted microbubbles were labeled with P-selectin and αV β3 -integrin antibodies. Control microbubbles were labeled with immunoglobulin G antibodies. First lymphosonography with Sonazoid (GE Healthcare, Oslo, Norway) was used to identify SLNs. Then dual-targeted and control microbubbles were injected intravenously to detect and quantify metastatic disease in the SLNs. Distant non-SLNs were imaged as benign controls. All evaluated lymph nodes (LNs) were surgically removed, and metastatic involvement was characterized by a histopathologic analysis. Two radiologists blinded to histopathologic results assessed the baseline B-mode images of LNs, and the results were compared to the histologic reference standard. The mean intensities of targeted and control microbubbles within the examined LNs were measured and compared to the LN histologic results. RESULTS Thirty-five SLNs and 34 non-SLNs from 13 Sinclair swine were included in this study. Twenty-one SLNs (62%) were malignant, whereas 100% of non-SLNs were benign. The sensitivity of B-mode imaging for metastatic LN diagnosis for both readers was relatively high (90% and 71%), but the specificity was very poor (50% and 58%). The sensitivity and specificity of molecular lymphosonography for metastatic LN detection were 91% and 67%, respectively. The mean intensities from dual-targeted microbubbles correlated well with the degree of metastatic LN involvement (r = 0.6; P

Radiation therapy is frequently used in the treatment of malignancies, but tumors are often more resistant than the surrounding normal tissue to radiation effects, because the tumor microenvironment is hypoxic. This manuscript details the fabrication and characterization of an ultrasound-sensitive, injectable oxygen microbubble platform (SE61(O2)) for overcoming tumor hypoxia. SE61(O2) was fabricated by first sonicating a mixture of Span 60 and water-soluble vitamin E purged with perfluorocarbon gas. SE61(O2) microbubbles were separated from the foam by flotation, then freeze dried under vacuum to remove all perfluorocarbon, and reconstituted with oxygen. Visually, SE61(O2) microbubbles were smooth, spherical, with an average diameter of 3.1 μm and were reconstituted to a concentration of 6.5 E7 microbubbles/ml. Oxygen-filled SE61(O2) provides 16.9 ± 1.0 dB of enhancement at a dose of 880 μl/l (5.7 E7 microbubbles/l) with a half-life under insonation of approximately 15min. In in vitro release experiments, 2 ml of SE61(O2) (1.3 E8 microbubbles) triggered with ultrasound was found to elevate oxygen partial pressures of 100 ml of degassed saline 13.8 mmHg more than untriggered bubbles and 20.6 mmHg more than ultrasound triggered nitrogen-filled bubbles. In preliminary in vivo delivery experiments, triggered SE61(O2) resulted in a 30.4 mmHg and 27.4 mmHg increase in oxygen partial pressures in two breast tumor mouse xenografts.

Author(s): Zablotska, Lydia B; Nadyrov, Eldar A; Rozhko, Alexander V; Gong, Zhihong; Polyanskaya, Olga N; McConnell, Robert J; O'Kane, Patrick; Brenner, Alina V; Little, Mark P; Ostroumova, Evgenia; Bouville, Andre; Drozdovitch, Vladimir; Minenko, Viktor; Demidchik, Yuri; Nerovnya, Alexander; Yauseyenka, Vassilina; Savasteeva, Irina; Nikonovich, Sergey; Mabuchi, Kiyohiko; Hatch, Maureen | Abstract: BackgroundRecent studies of children and adolescents who were exposed to radioactive iodine-131 (I-131) after the 1986 Chernobyl nuclear accident in Ukraine exhibited a significant dose-related increase in the risk of thyroid cancer, but the association of radiation doses with tumor histologic and morphologic features is not clear.MethodsA cohort of 11,664 individuals in Belarus who were aged ≤18 years at the time of the accident underwent 3 cycles of thyroid screening during 1997 to 2008. I-131 thyroid doses were estimated from individual thyroid activity measurements taken within 2 months after the accident and from dosimetric questionnaire data. Demographic, clinical, and tumor pathologic characteristics of the patients with thyroid cancer were analyzed using 1-way analysis of variance, chi-square tests or Fisher exact tests, and logistic regression.ResultsIn total, 158 thyroid cancers were identified as a result of screening. The majority of patients had T1a and T1b tumors (93.7%), with many positive regional lymph nodes (N1; 60.6%) but few distant metastases (M1; l1%). Higher I-131 doses were associated with higher frequency of solid and diffuse sclerosing variants of thyroid cancer (P l .01) and histologic features of cancer aggressiveness, such as lymphatic vessel invasion, intrathyroidal infiltration, and multifocality (all P l .03). Latency was not correlated with radiation dose. Fifty-two patients with self-reported thyroid cancers which were diagnosed before 1997 were younger at the time of the accident and had a higher percentage of solid variant cancers compared with patients who had screening-detected thyroid cancers (all P l .0001).ConclusionsI-131 thyroid radiation doses were associated with a significantly greater frequency of solid and diffuse sclerosing variants of thyroid cancer and various features of tumor aggressiveness.

Rationale and Objectives To use a cine balanced steady-state free precession magnetic resonance enterography (cine MRE) pulse sequence to assess the effectiveness of a sublingual (SL) antiperistaltic agent, hyoscyamine sulfate. Materials and Methods Institutional review board approval was granted with an exemption for informed consent in this Health Insurance Portability and Accountability Act–compliant, retrospective, single-institution study. Of the 288 MRE examinations performed between October 1, 2007 and January 15, 2011, 92 using SL hyoscyamine sulfate for antiperistalsis were included for review, each with cine MRE before and after medication. These 184 cine MRE data sets were randomized, blinded for treatment, and independently reviewed by five attending abdominal radiologists, who rated the degree of whole abdomen bowel motility on each cine MRE data set on a 5-point scale. Pre- and postmedication mean peristalsis ratings, standard deviation, mean difference, and treatment effect sizes were calculated. A repeated measures analysis of variance test was performed using a significance threshold of P = .05. Interobserver reliabilities were also calculated. Results Mean peristalsis ratings ranged 2.63–3.34 and 2.36–3.03, before and after medication administration, respectively. The mean differences ranged from 0.22 to 0.46, which are treatment effect sizes of 0.20 to 0.37. The decrease in peristalsis observed by the five reviewing radiologists after SL hyoscyamine sulfate administration was significant (df = 1/182, f = 7.35, P Conclusions Although cine MRE sequences show decreased bowel peristalsis after the use of SL hyoscyamine sulfate, the small size of the observed treatment effect is likely insufficient to justify its use for MRE.

To use subharmonic imaging (SHI) to depict the vascularity of pancreatic masses compared to contrast-enhanced endoscopic ultrasound (EUS) and pathologic results.Sixteen patients scheduled for biopsy of a pancreatic mass were enrolled in an Institutional Review Board-approved study. Pulse-inversion SHI (transmitting/receiving at 2.5/1.25 MHz) was performed on a LOGIQ 9 system (GE Healthcare, Milwaukee, WI) with a 4C transducer, whereas contrast harmonic EUS (transmitting/receiving at 4.7/9.4 MHz) was performed with a radial endoscope (GF-UTC180; Olympus Corporation, Tokyo, Japan) connected to a ProSound SSD α-10 scanner (Hitachi Aloka, Tokyo, Japan). Two injections of the contrast agent Definity (Lantheus Medical Imaging, North Billerica, MA) were administrated (0.3-0.4 and 0.6-0.8 mL for EUS and SHI, respectively). Contrast-to-tissue ratios (CTRs) in the mass and an adjacent vessel were calculated. Four physicians independently scored the images (benign to malignant) for diagnostic accuracy and inter-reader agreement.One patient dropped out before imaging, leaving 11 adenocarcinomas, 1 gastrointestinal stromal tumor with pancreatic infiltration, and 3 benign masses. Marked subharmonic signals were obtained in all patients, with intratumoral blood flow clearly visualized with SHI. Significantly greater CTRs were obtained in the masses with SHI than with EUS (mean ± SD, 1.71 ± 1.63 versus 0.63 ± 0.89; P = .016). There were no differences in the CTR in the surrounding vessels or when grouped by pathologic results (P .60). The accuracies for contrast EUS and SHI were low (53%), albeit with a greater κ value for SHI (0.34) than for EUS (0.13).Diagnostic accuracy of contrast EUS and transabdominal SHI for assessment of pancreatic masses was quite low in this pilot study. However, SHI had improved tumoral CTRs relative to contrast EUS.

Purpose Evaluate the reliability and validity of a standardized reporting system designed to improve communication between the clinician and radiologist regarding likelihood of hepatocellular carcinoma (HCC). Materials and Methods The system assigns liver lesions into 1 of 5 categories of estimated likelihood of HCC: 1, 95%. Six American Board of Radiology–certified radiologists reviewed 100 abdominal MRI studies (performed between September 2009 and June 2010 for HCC surveillance) blinded to the official reports and clinical information. Each reader recorded the highest category (1–5) assigned to any lesion per study. Reliability between readers was calculated by the Shrout-Fliess random sets intraclass correlation (ICC). To examine validity, original pretransplant reports from January 2009 to December 2010 were compared to pathology reports on liver explants. Sensitivities, specificities, predictive values, and receiver operating characteristic (ROC) curves were then produced. Results The ICC for retrospective readings was 0.80, indicating very good reliability. Of 45 pathologically proven cases, 16 category 1 or 2 cases were all free of HCC (negative predictive value 100%). Five of nine category 3 cases contained HCC. Six of eight category 4 cases contained HCC (PPV 75%). All 12 category 5 cases contained HCC (positive predictive value 100%). The area underneath the ROC curve was 0.949. If categories 1 and 2 are considered negative and categories 3–5 considered positive, this achieves 100% sensitivity with 73% specificity. Conclusion This standardized system for reporting likelihood of HCC, which is a forerunner of the recently introduced Liver Imaging Reporting and Data System, produces strong reliability and validity, while aiming to improve the clarity of clinical magnetic resonance imaging reports.

Imperfect detection on screening tests can lead to erroneous conclusions about the natural history of thyroid nodules following radiation exposure. Our objective was to assess in a repeatedly screened I-131-exposed population the frequency with which a thyroid nodule could be retrospectively identified on ultrasonography studies preceding the one on which it was initially detected.A cohort of over 13,000 young people exposed to fallout from Chornobyl underwent ultrasonography screening at 2-year intervals from 1998 to 2007. The study group consisted of screening examinations on which a thyroid nodule was detected following one or more prior negative examinations. In the study group there were 48 cancers and 92 benign nodules. For each of these 140 index studies a comparison set was created containing all available prior studies plus (to test for bias) negative studies from control subjects. While viewing the index study, three independent reviewers scored the comparison studies for the presence and size of a preexisting nodule. Detection rates were compared for true priors versus controls, for cancer versus benign, and for histologic subtypes of papillary carcinoma.A preexisting nodule was identified by at least one reviewer in 24.0% of the true prior versus 8.3% of the controls and by all three reviewers in 11% versus 1% (Fisher's exact test, p 0.0001). There was no significant difference in detection rates between cancers and benign nodules (22.4% vs. 24.7%, p = 0.411). There was no correlation between time from prior to index study and change in nodule size for either malignant or benign nodules (r = 0.01, NS). There were no differences in detection rates or size among papillary cancer subtypes. Reviewers could not distinguish between true priors and controls.These findings, showing significant rates of undetected benign and malignant nodules and no evidence for rapid growth, suggest that conclusions drawn from screening studies about the frequency of late-developing, rapidly growing thyroid nodules following radiation exposure should be interpreted with caution.

OBJECTIVE. Over time, the histology of papillary thyroid cancers detected in a repeatedly screened population exposed to radiation at Chornobyl (Chernobyl) has shifted from a more aggressive subtype toward less aggressive subtypes. This change may reflect biologic behavior but could also be influenced by the detectability of different subtypes. The study objective was to identify whether there is any relationship between the conspicuity of sonographically detected papillary cancers and histologic subtype.MATERIALS AND METHODS. Sonographic images of 84 papillary cancers occurring in young people exposed to radiation at Chornobyl were each given a conspicuity score using a subjective 1–5 scale by four independent expert readers blinded to histologic subtype. The effects of tumor subtype, tumor encapsulation, reader, machine type, and nodule size on sonographic conspicuity were determined using analysis of variance and Spearman correlations.RESULTS. Cancer subtype was related to sonographic conspicuity (p < ...

Purpose: To retrospectively evaluate the sensitivity, specificity, and positive and negative predictive values of steadystate free-precession (SSFP) survey MRI of the abdomen. Materials and Methods: A total of 375 consecutive outpatients underwent abdominal MRI at 1.5T. Excluding diffuse metastatic disease, 110 patients had at least one other clinically important finding. The SSFP survey included contiguous 5-mm-thick axial, sagittal, and coronal slices (total 90 slices) obtained during a total of 90 seconds of free breathing. Studies were reviewed by two experienced MRI readers independently, randomized, blinded, and at different sittings. The chi-squared test was used to compare SSFP to full MRI for showing clinically important findings. In a subset of 30 patients, confidence intervals (CI) were calculated to compare the accuracy of SSFP and full MRI as predictors of biopsy result. Results: SSFP detected 87.3% of clinically important findings and 93.3% of malignancies reported on the full MRI, with a 1.5% false-positive rate. Significant association was shown between SSFP and full MRI for clinically important findings (P 0.0001). Compared to biopsy, accuracy of SSFP was high (85% 12.7%), though not as high as full MRI (93.3% 8.8%). Conclusion: SSFP provides a rapid survey of the abdomen, with good sensitivity and few false positives.

© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. Several studies reported an increased risk of thyroid cancer in children and adolescents exposed to radioactive iodines, chiefly iodine-131 (131I), after the 1986 Chornobyl (Ukrainian spelling) nuclear power plant accident. The risk of benign thyroid tumors following such radiation exposure is much less well known. We have previously reported a novel finding of significantly increased risk of thyroid follicular adenoma in a screening study of children and adolescents exposed to the Chornobyl fallout in Ukraine. To verify this finding, we analyzed baseline screening data from a cohort of 11,613 individuals aged ≤18 years at the time of the accident in Belarus (mean age at screening = 21 years). All participants had individual131I doses estimated from thyroid radioactivity measurements and were screened according to a standardized protocol. We found a significant linear dose response for 38 pathologically confirmed follicular adenoma cases. The excess odds ratio per gray of 2.22 (95% confidence interval: 0.41, 13.1) was similar in males and females but decreased significantly with increasing age at exposure (P < 0.01), with the highest radiation risks estimated for those exposed at

Evaluate the reliability and validity of a standardized reporting system designed to improve communication between the clinician and radiologist regarding likelihood of hepatocellular carcinoma (HCC).The system assigns liver lesions into 1 of 5 categories of estimated likelihood of HCC: 1,5%; 2, 5%-20%; 3, 21%-70%; 4, 71%-95%; 5,95%. Six American Board of Radiology-certified radiologists reviewed 100 abdominal MRI studies (performed between September 2009 and June 2010 for HCC surveillance) blinded to the official reports and clinical information. Each reader recorded the highest category (1-5) assigned to any lesion per study. Reliability between readers was calculated by the Shrout-Fliess random sets intraclass correlation (ICC). To examine validity, original pretransplant reports from January 2009 to December 2010 were compared to pathology reports on liver explants. Sensitivities, specificities, predictive values, and receiver operating characteristic (ROC) curves were then produced.The ICC for retrospective readings was 0.80, indicating very good reliability. Of 45 pathologically proven cases, 16 category 1 or 2 cases were all free of HCC (negative predictive value 100%). Five of nine category 3 cases contained HCC. Six of eight category 4 cases contained HCC (PPV 75%). All 12 category 5 cases contained HCC (positive predictive value 100%). The area underneath the ROC curve was 0.949. If categories 1 and 2 are considered negative and categories 3-5 considered positive, this achieves 100% sensitivity with 73% specificity.This standardized system for reporting likelihood of HCC, which is a forerunner of the recently introduced Liver Imaging Reporting and Data System, produces strong reliability and validity, while aiming to improve the clarity of clinical magnetic resonance imaging reports.

Ocular melanoma is the most common adult primary intraocular tumour. Although

Background: Current knowledge about Chornobyl-related thyroid cancer risks comes from ecological studies based on grouped doses, case–control studies, and studies of prevalent cancers. Objective: To address this limitation, we evaluated the dose–response relationship for incident thyroid cancers using measurement-based individual iodine-131 (I-131) thyroid dose estimates in a prospective analytic cohort study. Methods: The cohort consists of individuals < 18 years of age on 26 April 1986 who resided in three contaminated oblasts (states) of Ukraine and underwent up to four thyroid screening examinations between 1998 and 2007 (n = 12,514). Thyroid doses of I-131 were estimated based on individual radioactivity measurements taken within 2 months after the accident, environmental transport models, and interview data. Excess radiation risks were estimated using Poisson regression models. Results: Sixty-five incident thyroid cancers were diagnosed during the second through fourth screenings and 73,004 person-years (PY) of observation. The dose–response relationship was consistent with linearity on relative and absolute scales, although the excess relative risk (ERR) model described data better than did the excess absolute risk (EAR) model. The ERR per gray was 1.91 [95% confidence interval (CI), 0.43–6.34], and the EAR per 104 PY/Gy was 2.21 (95% CI, 0.04–5.78). The ERR per gray varied significantly by oblast of residence but not by time since exposure, use of iodine prophylaxis, iodine status, sex, age, or tumor size. Conclusions: I-131–related thyroid cancer risks persisted for two decades after exposure, with no evidence of decrease during the observation period. The radiation risks, although smaller, are compatible with those of retrospective and ecological post-Chornobyl studies.

Background: Previous studies showed an increased risk of thyroid cancer among children and adolescents exposed to radioactive iodines released after the Chornobyl (Chernobyl) accident, but the effects of screening, iodine deficiency, age at exposure and other factors on the dose–response are poorly understood. Methods: We screened 11 970 individuals in Belarus aged 18 years or younger at the time of the accident who had estimated 131I thyroid doses based on individual thyroid activity measurements and dosimetric data from questionnaires. The excess odds ratio per gray (EOR/Gy) was modelled using linear and linear–exponential functions. Results: For thyroid doses

OBJECTIVE: Tegaserod is a 5-HT4 receptor partial agonist that increases peristaltic activity of the intestinal tract. It is approved for the treatment of patients with irritable bowel syndrome with constipation (IBS-C). IBS is a chronic gastrointestinal disorder of function that is reported to be associated with an increased incidence of abdominal surgery including cholecystectomy. The effect of tegaserod on nongut digestive organs, such as the gallbladder and biliary tract, has not been previously investigated. Therefore, this study aimed to evaluate the effects of tegaserod on gallbladder contractility and on functional status of the sphincter of Oddi during both the interdigestive and the digestive periods in healthy female subjects and in female patients with IBS-C. METHODS: During a 6-wk, double-blind, placebo-controlled crossover study, gallbladder contractility and concomitant change in luminal diameter of the common hepatic duct (CHD) and the common bile duct (CBD, both proximal and distal) in response to a standard liquid meal were quantified using real-time ultrasonography. Changes in luminal diameter of the CHD and the CBD were used as a surrogate marker for sphincter of Oddi function. Ultrasound measurements were conducted every 15 min from 45 min before, to 60 min after the test meal to observe the impact of tegaserod on gallbladder volume and any concomitant change in the diameters of the CHD and the CBD that developed in response to gallbladder contraction. The ultrasound measurements of gallbladder contractility, along with the CHD and the CBD diameters, were repeated after each of the two 2-wk periods of treatment with tegaserod or placebo. The recommended dose of tegaserod (6 mg b.i.d.) for IBS-C patients was used in healthy female subjects (n = 13) and female patients with IBS-C (n = 20). Twice this dose (12 mg b.i.d.) was also evaluated in an additional 20 female patients with IBS-C. Statistical evaluations were conducted using a two-sided analysis of variance (ANOVA). RESULTS: Gallbladder contractility variables including ejection fraction, ejection rate and ejection period, fasting and residual volume, and maximal emptying, were similar after 2 wk of treatment with tegaserod 6 mg b.i.d. and placebo in healthy female subjects and female patients with IBS-C. There were no significant changes in the luminal diameters of the CHD or the CBD after tegaserod compared to placebo in any cohort. Additionally, no significant dilation (≥7 mm in diameter) of the CHD or CBD was observed during maximal gallbladder emptying. Similar results were also observed when tegaserod was given at 12 mg b.i.d. in patients with IBS-C. Tegaserod treatment had no significant effect on plasma CCK concentration in response to the test meal. No significant abdominal pain or unexpected adverse events were reported during the study. CONCLUSIONS: This study showed no significant pharmacodynamic effect of tegaserod on gallbladder contractility or on CBD and CHD diameters as a surrogate marker of sphincter of Oddi function during both the interdigestive (fasting) and the digestive (postprandial) periods in healthy female subjects and female patients with IBS-C.

The debate about the relative influence of cultural and situational factors on welfare receipt is long standing. This study examines the competing effects of these factors. Results indicate that both culture and situation influence welfare receipt. Education and work experience were about three times as important as attitudes in explaining the variance in the number of years welfare was received.