Top-Down versus Bottom-Up Approach in Children Presenting with Urinary Tract Infection: Comparative Effectiveness Analysis Using RIVUR and CUTIE Data.

PURPOSE: The initial imaging approach to children with urinary tract infection (UTI) is controversial. Along with renal/bladder ultrasound, some advocate voiding cystourethrogram (VCUG), ie a bottom-up approach, while others advocate dimercaptosuccinic acid (DMSA) scan, ie a top-down approach. Comparison of these approaches is challenging. In the RIVUR/CUTIE trials, however, all subjects underwent both VCUG and DMSA scan. Our objective was to perform a comparative effectiveness analysis of the bottom-up vs top-down approach. MATERIALS AND METHODS: We simulated 1,000 hypothetical sets of 500 children using RIVUR/CUTIE data. In the top-down approach, patients underwent initial DMSA scan, and only those with renal scarring underwent VCUG. In the bottom-up approach, the initial study was VCUG. We assumed all children with vesicoureteral reflux (VUR) received continuous antibiotic prophylaxis (CAP). Outcomes included recurrent UTI, number of VCUGs and CAP exposure. We assumed a 25% VUR prevalence in children with initial UTI with sensitivity analysis using 40% VUR prevalence. RESULTS: Median age of the original RIVUR/CUTIE cohort was 12 months. First DMSA scan was performed at a median of 8.2 weeks (IQR 5-11.8) after the index UTI. In the simulated cohort, slightly higher yet statistically significantly recurrent UTI was associated with the top-down compared with the bottom-up approach (24.4% vs 18.0%, p=0.045). On the other hand, the bottom-up approach resulted in more VCUG (100% vs 2.4%, p <0.001). Top-down resulted in fewer CAP-exposed patients (25% vs 0.4%, p <0.001) and lower overall CAP exposure (5 vs 162 days/person, p <0.001). Sensitivity analysis was performed with 40% VUR prevalence with similar results. CONCLUSIONS: The top-down approach was associated with slightly higher recurrent UTI. Compared to the bottom-up approach, it significantly reduced the need for VCUG and CAP.

Full report on a survey of adverse reactions to radiopharmaceuticals from 1975 to 2017 in Japan.

OBJECTIVE: This pharmacovigilance-based survey was aimed at determining the prevalence of, and association between, radiopharmaceuticals and adverse reactions to radiopharmaceuticals from 1975 to 2017 in Japan. METHODS: The Subcommittee for Safety Issues of Radiopharmaceuticals of the Japan Radioisotope Association's Medical Science and Pharmaceutical Committee mailed a form for reporting adverse reactions to radiopharmaceuticals to all institutes performing nuclear medicine examinations in Japan. This investigation included adverse reactions to diagnostic radiopharmaceuticals labeled with both single-photon- and positron-emitting radionuclides and therapeutic sodium iodide labeled with 131I. Each institute returned the reporting form to the subcommittee each time an adverse reaction occurred. RESULTS: Replies were obtained from 75% of the institutions. In total, 1099 adverse reactions were reported from 46,645,580 radiopharmaceutical administrations, giving a prevalence of 2.4 adverse reactions per 100,000 administrations (95% confidence interval 2.2-2.5). Adverse reactions were most frequently observed for 131I-iodomethylnorcholesterol (230.1/105 administrations), followed by 131I-HSA (76.3/105 administrations), 131I-sodium iodohippurate (31.2/105 administrations), and 99mTc-DTPA (12.0/105 administrations). Comparison of adverse reactions between before and after 1997 revealed that prevalence dropped from 3.7/105 administrations (95% confidence interval 3.5-4.1) to 1.5/105 administrations (95% confidence interval 1.4-1.6). During the study period, vasovagal reactions accounted for 50.3% of adverse reactions, fever for 7.5%, allergic reactions for 25.7%, and other for 16.5%; 3.7% of all adverse reactions were considered severe but none were lethal. A definite, probable, possible, less likely, and uncertain causal relationship with radiopharmaceuticals was observed in 13.1%, 33.7%, 39.9%, 6.2%, and 7.1% of adverse reactions, respectively. CONCLUSIONS: These results suggest that nuclear medicine staff must be aware of the possibility of adverse reactions from radiopharmaceuticals, despite their rarity.

Barriers and pathways to informed consent for ionising radiation imaging examinations: A qualitative study.

INTRODUCTION: Informed consent for ionising radiation medical imaging examinations represents a recent change to medical imaging practice. This practice has not had a definitive and authoritative integration into clinical practice, and lack of direction has caused many health care professionals to be unsure of an appropriate consent methodology. Consent practices have been undertaken inconsistently and sometimes poorly. This research sought to investigate what barriers exist to meaningful informed consent, and what pathways are suggested to overcome these barriers. These views are then discussed in the context of practical health care consent practices. METHODS: A semi-structured interview explored the views of radiographers and radiologists on the practice of disclosing the ionising radiation risk of a clinical medical imaging examination. Qualitative data was analysed using a nominal method of quantitative transformation. Responses were reviewed, and a set of definitive themes constructed. Participants considered the influences, logistics and barriers to the informed consent process. Participants were then asked what pathways might be developed that would improve the process. RESULTS: Twenty-one (21) radiographer participants and nine (9) radiologists were interviewed. The barriers to consent identified issues of time constraints, lack of a unified message, and patient presentations. Pathways suggested included limiting the scope of the consent practice, sharing the consent responsibility, and formulation of definitive consent guidelines. CONCLUSION: A unified, definitive series of guidelines for informed consent for ionising radiation examinations would alleviate many of the identified barriers. Having the consent process consistently begin with the referring doctor would facilitate more meaningful consent.

Intensive Imaging Surveillance of Survivors of Breast Cancer May Increase Risk of Radiation-induced Malignancy.

BACKGROUND: Current clinical guidelines recommend mammography as the only imaging method for surveillance in asymptomatic survivors of early breast cancer (EBC). However, non-recommended tests are commonly used. We estimated the imaging radiation-induced malignancies (IRIM) risks in survivors of EBC undergoing different imaging surveillance models. MATERIALS AND METHODS: We built 5 theoretical models of imaging surveillance, from annual mammography only (model 1) to increasingly imaging-intensive approaches, including computed tomography (CT) scan, positron emission tomography-CT, bone scan, and multigated acquisition scan (models 2 through 5). Using the National Cancer Institute's Radiation Risk Assessment Tool, we compared the excess lifetime attributable cancer risk (LAR) for hypothetical survivors of EBC starting surveillance at the ages of 30, 60, or 75 years and ending at 81 years. RESULTS: For all age groups analyzed, there is a statistically significant increase in LAR when comparing model 1 with more intensive models. As an example, in a patient beginning surveillance at the age of 60 years, there is a 28.5-fold increase in the IRIM risk when comparing mammography only versus a schedule with mammography plus CT scan of chest-abdomen and bone scan. We found no differences when comparing models 2 through 5. LAR is higher when surveillance starts at a younger age, although the age effect was only statistically significant in model 1. CONCLUSION: Non-recommended imaging during EBC surveillance can be associated with a significant increase in LAR. In addition to the lack of survival benefit, additional tests may have significant IRIM risks and should be avoided.

What about sentinel lymph node biopsy for early breast cancer during pregnancy?

Pregnancy-associated breast cancer is rare, but this clinical situation arises in 1/10,000-1/3000 pregnancies. In patients presenting an early-stage breast tumor devoid of clinically pathological lymph node, sentinel lymph node (SLN) biopsy has not yet been validated as a routine procedure for pregnant women due to the lack of data in the literature. The blue dye injection is not recommended because of 2% theoretical risk of anaphylactic shock. Several studies have shown that Tc99m injection at conventional dose between 12.1 and 18.5MBq exposed the fetus to an irradiation between 0.011 and 0.0245mSv much below the 50mSv recommended threshold. As evidenced by lymphoscintigraphy scans, the dose of injected Tc99m is localized at the injection site and in the SLN. According to the literature, the SLN technique does not seem to impact the fetal or obstetrical prognosis. Studies involving larger cohorts are required to confirm these data and to indicate this technique in pregnant women. Considering the benefit for the patient and the low risk incurred on both fetal and obstetrical levels, it appears reasonable to discuss the indication of SLN on a case-by-case basis in multidisciplinary oncologic meetings.

[The choice of diagnostic modality for acute pulmonary embolism].

The diagnosis of pulmonary embolism (PE) relies on clinical assessment, D-dimer test and diagnostic imaging. Modern CT pulmonary angiography (CTPA), ventilation/perfusion  single-photon emission computed tomography (SPECT) and SPECT/CT are rather equal in terms of sensitivity, specificity and inconclusive results for the diagnosis of PE, outper-forming planar lung scintigraphy. Furthermore, SPECT/CT and CTPA can both provide important information regarding differential diagnoses. Thus, the choice of primary diag-nostic modality relies on local expertise, availability and special circumstances like radiation dose, contraindications and the clinical urgency.

Lung uptake during 99mTc-hydroxymethylene diphosphonate scintigraphy in patient with TTR cardiac amyloidosis: An underestimated phenomenon.

BACKGROUND: Full body scintigraphy using bone tracers plays an important role in defining the type of amyloidosis and in diagnosing the heart involvement (cardiac amyloidosis, CA). No study has been conducted to explore lung retention (LR) in CA and its correlation to heart retention (HR).We evaluated LR in patients undergoing 99mTc-HMDP scintigraphy during evaluation for suspected CA. METHODS AND RESULTS: We enrolled 93 suspected CA patients. Patients underwent a complete diagnostic work up. After diagnostic process 82 patients resulted affected by certain CA (20 AL and 62 TTR), while 11 subjects showed left ventricular hypertrophy (LVH) not caused by CA. 99mTc-HMDP cardiac uptake was evaluated using the Perugini visual score while the modified Janssen score was used for LR estimation (grade 0 no uptake, grade 1 less than ribs, grade 2 more than ribs). RESULTS: 99mTc-HMDP LR was observed in 1/20 AL patient (5%), while 36/62 (58%) TTR patients showed LR with 29 grade 1 (47%) and 7 grade 2 (11%). No LR was observed in patients with LVH and no CA. LR was not evident in patients without HR, present in 1/3 (33%) of the patients with Perugini 1 HR and 11/24 (46%) and 26/36 (72%) of the patients showing respectively a Perugini 2 and a Perugini 3. CONCLUSION: 99mTc-HMDP scintigraphy shows LR in about 60% of TTR subjects, related to the grade of HR. In AL amyloidosis LR is less frequent than in TTR amyloidosis suggesting an aetiological tropism that seems comparable to the already known TTR related cardiac tropism.

Safety and feasibility of breast lesion localization using magnetic seeds (Magseed): a multi-centre, open-label cohort study.

PURPOSE: Wire localization has several disadvantages, notably wire migration and difficulty scheduling the procedure close to surgery. Radioactive seed localization overcomes these disadvantages, but implementation is limited due to radiation safety requirements. Magnetic seeds potentially offer the logistical benefits and transcutaneous detection equivalence of a radioactive seed, with easier implementation. This study was designed to evaluate the feasibility and safety of using magnetic seeds for breast lesion localization. METHODS: A two-centre open-label cohort study to assess the feasibility and safety of magnetic seed (Magseed) localization of breast lesions. Magseeds were placed under radiological guidance into women having total mastectomy surgery. The primary outcome measure was seed migration distance. Secondary outcome measures included accuracy of placement, ease of transcutaneous detection, seed integrity and safety. RESULTS: Twenty-nine Magseeds were placed into the breasts of 28 patients under ultrasound guidance. There was no migration of the seeds between placement and surgery. Twenty-seven seeds were placed directly in the target lesion with the other seeds being 2 and 3 mm away. All seeds were detectable transcutaneously in all breast sizes and at all depths. There were no complications or safety issues. CONCLUSIONS: Magnetic seeds are a feasible and safe method of breast lesion localization. They can be accurately placed, demonstrate no migration in this feasibility study and are detectable in all sizes and depths of breast tissue. Now that safety and feasibility have been demonstrated, further clinical studies are required to evaluate the seed's effectiveness in wide local excision surgery.

Germline Variants in DNA Repair Genes, Diagnostic Radiation, and Risk of Thyroid Cancer.

Background: Radiation exposure is a well-documented risk factor for thyroid cancer; diagnostic imaging represents an increasing source of exposure. Germline variations in DNA repair genes could increase risk of developing thyroid cancer following diagnostic radiation exposure. No studies have directly tested for interaction between germline mutations and radiation exposure.Methods: Using data and DNA samples from a Connecticut population-based case-control study performed in 2010 to 2011, we genotyped 440 cases of incident thyroid cancer and 465 population-based controls for 296 SNPs in 52 DNA repair genes. We used multivariate unconditional logistic regression models to estimate associations between each SNP and thyroid cancer risk, as well as to directly estimate the genotype-environment interaction between each SNP and ionizing radiation.Results: Three SNPs were associated with increased risk of thyroid cancer and with thyroid microcarcinoma: HUS rs2708896, HUS rs10951937, and MGMT rs12769288. No SNPs were associated with increased risk of larger tumor (>10 mm) in the additive model. The gene-environment interaction analysis yielded 24 SNPs with Pinteraction < 0.05 for all thyroid cancer, 12 SNPs with Pinteraction < 0.05 for thyroid microcarcinoma, and 5 SNPs with Pinteraction < 0.05 for larger tumors.Conclusions: Germline variants in DNA repair genes are associated with thyroid cancer risk and are differentially associated with thyroid microcarcinoma and large tumor size. Our study provides the first evidence that germline genetic variations modify the association between diagnostic radiation and thyroid cancer risk.Impact: Thyroid microcarcinoma may represent a distinct subset of thyroid cancer. The effect of diagnostic radiation on thyroid cancer risk varies by germline polymorphism. Cancer Epidemiol Biomarkers Prev; 27(3); 285-94. ©2017 AACR.

Safety of coronary CT angiography and functional testing for stable chest pain in the PROMISE trial: A randomized comparison of test complications, incidental findings, and radiation dose.

BACKGROUND: Coronary computed tomography angiography (CTA) and functional testing strategies for stable chest pain yield similar outcomes; one aspect that may guide test choice is safety. METHODS: We compared test safety (test complications, incidental findings, and effective radiation dose) between CTA and functional testing as-tested in PROMISE (PROspective Multicenter Imaging Study for Evaluation of Chest Pain). In the subgroup whose physicians intended nuclear stress over other functional tests if randomized to the functional arm, we compared radiation dose of CTA versus nuclear stress and identified characteristics associated with dose. RESULTS: Of 9470 patients, none had major and <1% had minor complications (CTA: 0.8% [37/4633] vs. functional: 0.6% [27/4837]). CTA identified more incidental findings (11.6% [539/4633] vs. 0.7% [34/4837], p < 0.001), most commonly pulmonary nodules (9.4%, 437/4633). CTA had similar 90-day cumulative radiation dose to functional testing. However, in the subgroup whose physicians intended nuclear stress (CTA 3147; nuclear 3203), CTA had lower median index test (8.8 vs. 12.6 mSv, p < 0.001) and 90-day cumulative (11.6 vs. 13.1 mSv, p < 0.001) dose, independent of patient characteristics. The lowest nuclear doses employed 1-day Tc-99m protocols (12.2 mSv). The lowest CTA doses were at sites performing ≥500 CTAs/year (6.9 mSv) and with advanced (latest available) CT scanners (5.5 mSv). CONCLUSION: Complications were negligibly rare for both CTA and functional testing. CTA detects more incidental findings. Compared to nuclear stress testing, CTA's lower radiation dose, independent of patient characteristics, makes it an attractive test choice. Radiation dose varies with imaging protocol, indicating opportunities to further reduce dose. (ClinicalTrials.gov number, NCT01174550).

Radiation Safety in Children With Congenital and Acquired Heart Disease: A Scientific Position Statement on Multimodality Dose Optimization From the Image Gently Alliance.

There is a need for consensus recommendations for ionizing radiation dose optimization during multimodality medical imaging in children with congenital and acquired heart disease (CAHD). These children often have complex diseases and may be exposed to a relatively high cumulative burden of ionizing radiation from medical imaging procedures, including cardiac computed tomography, nuclear cardiology studies, and fluoroscopically guided diagnostic and interventional catheterization and electrophysiology procedures. Although these imaging procedures are all essential to the care of children with CAHD and have contributed to meaningfully improved outcomes in these patients, exposure to ionizing radiation is associated with potential risks, including an increased lifetime attributable risk of cancer. The goal of these recommendations is to encourage informed imaging to achieve appropriate study quality at the lowest achievable dose. Other strategies to improve care include a patient-centered approach to imaging, emphasizing education and informed decision making and programmatic approaches to ensure appropriate dose monitoring. Looking ahead, there is a need for standardization of dose metrics across imaging modalities, so as to encourage comparative effectiveness studies across the spectrum of CAHD in children.

Evaluation of the radiation dose exposure and associated cancer risks in patients having preoperative parathyroid localization.

OBJECTIVE The study aimed to evaluate the total effective and organ absorbed radiation doses associated with three- and four-phase parathyroid computed tomography (CT) and sestamibi scans used for the preoperative localisation of parathyroid adenomas in a cohort of patients with primary hyperparathyroidism at a single institution. We aimed to assess the risk of cancer incidence for the organs demonstrating the highest absorbed doses for the different imaging techniques, and more specifically determine the risk for our cohort of patients. METHODS Fifty patients with primary hyperparathyroidism had both multiphase CT and sestamibi scans. The Imaging Performance Assessment of CT Scanners (ImPACT) calculator was used to estimate the patient-effective and organ-absorbed radiations doses for all the CT examinations. For sestamibi scans, the US Nuclear Regulatory Commission NUREG/CR-6345 publication was used to estimate the dose for each patient. The attributable risks of cancer were calculated using the Health Protection Agency HPA-CRCE-028 publication. RESULTS The mean patient total effective doses were 15.9% ± 2.8 mSv, 20.2% ± 2.8  mSv and 5.6 ± 0.24 mSv for three-phase CT, four-phase CT and sestamibi examinations, respectively. In our cohort, the highest attributable lifetime risk was for lung cancer (0.03%) after multiphase CT. This compared with a tenfold lower risk for thyroid cancer (0.003%). After sestamibi, the highest risk was for colon cancer (0.06%). CONCLUSIONS Multiphase CT is associated with a higher radiation dose and thus a higher potential risk of cancer, but this risk is low in the older population that constituted the majority of our cohort.

The Burden of Ionizing Radiation Studies in Children with Ventricular Shunts.

OBJECTIVES: To quantify the number of shunt-related imaging studies that patients with ventricular shunts undergo and to calculate the proportion of computed tomography (CT) scans associated with a surgical intervention. STUDY DESIGN: Retrospective longitudinal cohort analysis of patients up to age 22 years with a shunt placed January 2002 through December 2003 at a pediatric hospital. Primary outcome was the number of head CT scans, shunt series radiograph, skull radiographs, nuclear medicine, and brain magnetic resonance imaging studies for 10 years following shunt placement. Secondary outcome was surgical interventions performed within 7 days of a head CT. Descriptive statistics were used for analysis. RESULTS: Patients (n = 130) followed over 10 years comprised the study cohort. The most common reasons for shunt placement were congenital hydrocephalus (30%), obstructive hydrocephalus (19%), and atraumatic hemorrhage (18%), and 97% of shunts were ventriculoperitoneal. Patients underwent a median of 8.5 head CTs, 3.0 shunt series radiographs, 1.0 skull radiographs, 0 nuclear medicine studies, and 1.0 brain magnetic resonance imaging scans over the 10 years following shunt placement. The frequency of head CT scans was greatest in the first year after shunt placement (median 2.0 CTs). Of 1411 head CTs in the cohort, 237 resulted in surgical intervention within 7 days (17%, 95% CI 15%-19%). CONCLUSIONS: Children with ventricular shunts have been exposed to large numbers of imaging studies that deliver radiation and most do not result in a surgical procedure. This suggests a need to improve the process of evaluating for ventricular shunt malfunction and minimize radiation exposure.