Outcomes of ATA Low-Risk Pediatric Thyroid Cancer Patients Not Treated With Radioactive Iodine Therapy.

CONTEXT: The American Thyroid Association (ATA) Pediatric Guidelines recommend patients not receive radioactive iodine therapy (RAIT) for differentiated thyroid cancer (DTC) confined to the thyroid. Since publication, there is ongoing concern whether withholding RAIT will result in a lower rate of remission. OBJECTIVE: This study explores whether ATA low-risk patients treated with and without RAIT achieved similar remission rates. METHODS: Medical records of patients <19 years old diagnosed with DTC and treated with total thyroidectomy between 2010 and 2020 were reviewed. Multivariate logistic regression was performed to evaluate factors influencing RAIT administration and remission rate. RESULTS: Ninety-five patients with ATA low-risk DTC were analyzed: 53% (50/95) and 47% (45/95) were treated with and without RAIT, respectively. RAIT was used to treat 82% of patients before 2015 compared with 33% of patients after 2015 (P < .01). No significant difference in 1-year remission rate was found between patients treated with and without RAIT, 70% (35/50) vs 69% (31/45), respectively. With longer surveillance, remission rates increased to 82% and 76% for patients treated with and without RAIT, respectively. Median follow-up was 5.8 years (IQR 4.3-7.9, range 0.9-10.9) and 3.6 years (IQR 2.7-6.6; range 0.9-9.3) for both cohorts. No risk factors for persistent or indeterminate disease status were found, including RAIT administration, N1a disease, and surgery after 2015. CONCLUSION: Withholding RAIT for pediatric patients with ATA low-risk DTC avoids exposure to radiation and does not have a negative impact on remission rates. Dynamic risk stratification at 1-year after initial treatment is a suitable time point to assess the impact of withholding RAIT for these patients.

Summary: Appropriate Use Criteria for Lymphoscintigraphy in Sentinel Node Mapping and Lymphedema/Lipedema.

Expert representatives from 11 professional societies, as part of an autonomous work group, researched and developed appropriate use criteria (AUC) for lymphoscintigraphy in sentinel lymph node mapping and lymphedema. The complete findings and discussions of the work group, including example clinical scenarios, were published on October 8, 2022, and are available at https://www.snmmi.org/ClinicalPractice/content.aspx?ItemNumber=42021 The complete AUC document includes clinical scenarios for scintigraphy in patients with breast, cutaneous, and other cancers, as well as for mapping lymphatic flow in lymphedema. Pediatric considerations are addressed. These AUC are intended to assist health care practitioners considering lymphoscintigraphy. Presented here is a brief overview of the AUC, including the rationale and methodology behind development of the document. For detailed findings of the work group, the reader should refer to the complete AUC document online.

Celebrating eighty years of radionuclide therapy and the work of Saul Hertz.

March 2021 will mark the eightieth anniversary of targeted radionuclide therapy, recognizing the first use of radioactive iodine to treat thyroid disease by Dr. Saul Hertz on March 31, 1941. The breakthrough of Dr. Hertz and collaborator physicist Arthur Roberts was made possible by rapid developments in the fields of physics and medicine in the early twentieth century. Although diseases of the thyroid gland had been described for centuries, the role of iodine in thyroid physiology had been elucidated only in the prior few decades. After the discovery of radioactivity by Henri Becquerel in 1897, rapid advancements in the field, including artificial production of radioactive isotopes, were made in the subsequent decades. Finally, the diagnostic and therapeutic use of radioactive iodine was based on the tracer principal that was developed by George de Hevesy. In the context of these advancements, Hertz was able to conceive the potential of using of radioactive iodine to treat thyroid diseases. Working with Dr. Roberts, he obtained the experimental data and implemented it in the clinical setting. Radioiodine therapy continues to be a mainstay of therapy for hyperthyroidism and thyroid cancer. However, Hertz struggled to gain recognition for his accomplishments and to continue his work and, with his early death in 1950, his contributions have often been overlooked until recently. The work of Hertz and others provided a foundation for the introduction of other radionuclide therapies and for the development of the concept of theranostics.

Reducing radiation dose from myocardial perfusion imaging in subjects with complex congenital heart disease.

INTRODUCTION: The prevalence of defects and effective radiation dose from various myocardial perfusion imaging (MPI) strategies in congenital heart disease (CHD) is unknown. METHODS: We studied 75 subjects with complex CHD (ages 5 to 80 years) referred for MPI between 2002 and 2015. A rest and exercise or pharmacologic stress MPI was performed using 99mTechnetium sestamibi, 82rubidium or 13N-ammonia, and Sodium iodide SPECT (single-photon emission computed tomography), SPECT/CT or Cadmium zinc telluride (CZT) SPECT or PET (positron emission tomography)/CT scanners. Deidentified images were interpreted semi-quantitatively in three batches: stress only MPI, stress/rest MPI, and stress/rest MPI with taking into account a history of ventricular septal defect repair. Effective radiation dose was estimated for stress/rest MPI and predicted for 1-day stress-first (normal stress scans), and for 2-day stress/rest MPI (abnormal stress scans). RESULTS: The median age was 18.6 years. The most common type of CHD was transposition of the great arteries (63%). Rest/stress MPI was abnormal in 43% of subjects and 25% of the abnormal scans demonstrated reversible defects. Of the subjects with abnormal MPI, 33% had significant underlying anatomic coronary artery obstruction. Estimated mean effective radiation dose ranged from 2.1 ± 0.6 mSv for 13N-ammonia PET/CT to 12.5 ± 0.9 mSv for SPECT/CT. Predicted effective radiation dose was significantly lower for stress-first MPI and for 2-day stress/rest protocols. CONCLUSIONS: Due to the relatively high prevalence of abnormal stress MPI, tailored protocols with a stress-first MPI as well as the use of 2-day protocols and advanced imaging technologies including CZT SPECT, novel image reconstruction software, and PET MPI could substantially reduce radiation dose in complex CHD.

Chronic Acalculous Cholecystitis in Children With Biliary Symptoms: Usefulness of Hepatocholescintigraphy.

OBJECTIVES: Chronic acalculous cholecystitis (CAC) increasingly is being diagnosed as a cause of recurring biliary symptoms in children, but its clinical diagnosis remains challenging. The primary objective was to evaluate the utility of hepatocholescintigraphy in pediatric patients with suspected CAC. A secondary objective was to describe their clinical follow-up after diagnosis. METHODS: Medical records of patients (aged 9-20 years) who underwent hepatocholescintigraphy from February 2008 to January 2012 were reviewed. Patients with gallstones, and with ≤1 year of clinical follow-up, and studies without gallbladder (GB) stimulation were excluded. GB ejection fraction (GBEF) of <35% after sincalide or fatty meal (Lipomul) stimulation were considered abnormal. Diagnosis of CAC was based on histopathology after cholecystectomy. Patients with negative GB pathology, or complete resolution of symptoms without surgery, or alternative diagnoses for persistent symptoms were considered to not have CAC. RESULTS: Eighty-three patients formed the study group (median age 14.9 years), of which 81.9% were girls. Median duration of symptoms and clinical follow-up were 6 months and 2.9 years, respectively. Fifty-two patients had at least 1 study with sincalide and 36 patients had at least 1 study with Lipomul. Initial cholescintigraphy was 95.0% sensitive and 73.0% specific in diagnosing CAC, with a negative predictive value of 97.9%. Of the 31 patients with abnormal GBEF, 22 underwent cholecystectomy with improvement in pain in 72.7%, whereas all of the 9 without surgery improved. CONCLUSIONS: Hepatocholescintigraphy is useful for excluding CAC, although the clinical implications of an abnormal GBEF need to be further defined.

Esophageal transit scintigraphy in children: a user's guide and pictorial review.

Technical and clinical aspects of esophageal transit scintigraphy in pediatric patients are reviewed via several illustrative cases that highlight its utility in evaluating primary and secondary esophageal motility disorders.

Implementation of a Flipped Classroom for Nuclear Medicine Physician CME.

INTRODUCTION: Increasingly, emerging technologies are expanding instructional possibilities, with new methods being adopted to improve knowledge acquisition and retention. Within medical education, many new techniques have been employed in the undergraduate setting, with less utilization thus far in the continuing medical education (CME) sphere. This paper discusses the use of a new method for CME-the "flipped classroom," widely used in undergraduate medical education. This method engages learners by providing content before the live ("in class") session that aids in preparation and fosters in-class engagement. METHODS: A flipped classroom method was employed using an online image-rich case-based module and quiz prior to a live CME session at a national nuclear medicine meeting. The preparatory material provided a springboard for in-depth discussion at the live session-a case-based activity utilizing audience response technology. Study participants completed a survey regarding their initial experience with this new instructional method. In addition, focus group interviews were conducted with session attendees who had or had not completed the presession material; transcripts were qualitatively analyzed. RESULTS: Quantitative survey data (completed by two-thirds of the session attendees) suggested that the flipped method was highly valuable and met attendee educational objectives. Analysis of focus group data yielded six themes broadly related to two categories-benefits of the flipped method for CME and programmatic considerations for successfully implementing the flipped method in CME. DISCUSSION: Data from this study have proven encouraging and support further investigations around the incorporation of this innovative teaching method into CME for nuclear imaging specialists.

Pretransplant functional imaging and outcome in pediatric patients with relapsed/refractory Hodgkin lymphoma undergoing autologous transplantation.

BACKGROUND: Pretransplant functional imaging (FI), particularly a negative positron emission tomography (PET), is a strong predictor of outcome in adults with relapsed or refractory Hodgkin lymphoma (HL), but data in pediatrics are limited. METHODS: The medical records of 49 consecutive pediatric patients, who received autologous transplant at a single institution, were retrospectively analyzed. All patients had either gallium or PET scan before transplant and were conditioned with carmustine, etoposide, cytarabine, and melphalan (BEAM). Deauville scores were retrospectively assigned for patients with PET (score ≥ 4 positive). RESULTS: Of the 49 patients (median age, 16.2 years), 41 (84%) were pretransplant FI negative and eight (16%) were pretransplant FI positive, after first- to fourth-line salvage therapy, and a median of two salvage cycles. Eighteen patients (37%) received posttransplant radiation. At a median follow up of 46 months, 45 patients (92%) were alive and disease free, and there were three nonrelapse deaths and only one relapse death (Deauville score of 5). The 4-year progression-free survival (PFS) for the entire cohort was 92% (95% confidence interval [CI]: 78-97), and PFS based on pretransplant disease status was 95% (95% CI: 82-99%) in the negative FI group versus 75% (95% CI: 31-93) if positive FI (P = 0.057). CONCLUSION: Our analysis revealed outstanding outcomes for children and adolescents with relapsed/refractory HL. There were too few relapses to identify the predictive value of pretransplant metabolic status, but pediatric patients with relapsed/refractory HL and a negative pretransplant FI had excellent survival.

How we read pediatric PET/CT: indications and strategies for image acquisition, interpretation and reporting.

PET/CT plays an important role in the diagnosis, staging and management of many pediatric malignancies. The techniques for performing PET/CT examinations in children have evolved, with increasing attention focused on reducing patient exposure to ionizing radiation dose whenever possible and minimizing scan duration and sedation times, with a goal toward optimizing the overall patient experience. This review outlines our approach to performing PET/CT, including a discussion of the indications for a PET/CT exam, approaches for optimizing the exam protocol, and a review of different approaches for acquiring the CT portion of the PET/CT exam. Strategies for PACS integration, image display, interpretation and reporting are also provided. Most practices will develop a strategy for performing PET/CT that best meets their respective needs. The purpose of this article is to provide a comprehensive overview for radiologists who are new to pediatric PET/CT, and also to provide experienced PET/CT practitioners with an update on state-of-the art CT techniques that we have incorporated into our protocols and that have enabled us to make considerable improvements to our PET/CT practice.

Diagnostic Accuracy of Lymphoscintigraphy for Lymphedema and Analysis of False-Negative Tests.

Lymphedema is the chronic enlargement of tissue due to inadequate lymphatic function. Diagnosis is made by history and physical examination and confirmed with lymphoscintigraphy. The purpose of this study was to assess the accuracy of lymphoscintigraphy for the diagnosis of lymphedema and to determine characteristics of patients with false-negative tests. METHODS: Individuals referred to our lymphedema program with "lymphedema" between 2009 and 2016 were analyzed. Subjects were assessed by history, physical examination, and lymphoscintigraphy. Patient age at presentation, duration of lymphedema, location of disease, gender, previous infections, and lymphedema type were analyzed. RESULTS: The study included 227 patients (454 limbs); lymphedema was diagnosed clinically in 169 subjects and confirmed by lymphoscintigraphy in 162 (117 primary, 45 secondary; 96% sensitivity). Fifty-eight patients were thought to have a condition other than lymphedema, and all had negative lymphoscintigrams (100% specificity). A subgroup analysis of the 7 individuals with lymphedema clinically, but normal lymphoscintigrams, showed that all had primary lymphedema; duration of disease and infection history were not different between true-positive and false-negative lymphoscintigram results (P = 0.5). Two patients with a false-negative test underwent repeat lymphoscintigraphy, which then showed lymphatic dysfunction consistent with lymphedema. CONCLUSION: Lymphoscintigraphy is very sensitive and specific for lymphedema. All patients with false-negative studies had primary lymphedema. A patient with a high clinical suspicion of lymphedema and a normal lymphoscintigram should be treated conservatively for the disease and undergo repeat lymphoscintigraphy.

Saul Hertz, MD, and the birth of radionuclide therapy.

The year, 2016, marked the 75th anniversary of Dr. Saul Hertz first using radioiodine to treat a patient with thyroid disease. In November of 1936, a luncheon was held of the faculty of Harvard Medical School where Karl Compton, PhD, president of the Massachusetts Institute of Technology was invited to give a presentation entitled "What Physics Can Do for Biology and Medicine." Saul Hertz who attended the luncheon spontaneously asked the very pertinent question that perhaps changed the course of treatment of thyroid disease, "Could iodine be made radioactive artificially?" We review the events leading up to the asking of this question, the preclinical investigations by Dr. Hertz and his colleague Arthur Roberts prior to the treatment of the first patient and what occurred in the years following this landmark event. This commentary seeks to set the record straight to the sequence of events leading to the first radioiodine therapy, so that those involved can be recognized with due credit.

Evaluation of the utility of 99m Tc-MDP bone scintigraphy versus MIBG scintigraphy and cross-sectional imaging for staging patients with neuroblastoma.

PURPOSE: Accurate staging of neuroblastoma requires multiple imaging examinations. The purpose of this study was to determine the relative contribution of 99m Tc-methylene diphosphonate (MDP) bone scintigraphy (bone scan) versus metaiodobenzylguanidine scintigraphy (MIBG scan) for accurate staging of neuroblastoma. METHODS: A medical record search by the identified patients with neuroblastoma from 1993 to 2012 who underwent both MIBG and bone scan for disease staging. Cross-sectional imaging was used to corroborate the scintigraphy results. Clinical records were used to correlate imaging findings with clinical staging and patient management. RESULTS: One hundred thirty-two patients underwent both MIBG and bone scan for diagnosis. All stage 1 (n = 12), 2 (n = 8), and 4S (n = 4) patients had a normal bone scan with no skeletal MIBG uptake. Six of 30 stage 3 patients had false (+) bone scans. In the 78 stage 4 patients, 58/78 (74%) were both skeletal MIBG(+)/bone scan (+). In 56 of the 58 cases, skeletal involvement detected with MIBG was equal to or greater than that detected by bone scan. Only 3/78 had (-) skeletal MIBG uptake and (+) bone scans; all 3 had other sites of metastatic disease. Five of 78 had (+) skeletal MIBG with a (-) bone scan, while 12/78 had no skeletal involvement by either MIBG or bone scan. In no case did a positive bone scan alone determine a stage 4 designation. CONCLUSION: In the staging of neuroblastoma, 99m Tc-MDP bone scintigraphy does not identify unique sites of disease that affect disease stage or clinical management, and in the majority of cases bone scans can be omitted from the routine neuroblastoma staging algorithm.

Massive Localized Lymphedema: A Case-Control Study.

BACKGROUND: Massive localized lymphedema (MLL) is an area of skin and subcutaneous overgrowth associated with obesity. The purpose of this study was to determine whether MLL results from obesity-induced lymphedema (OIL) and to characterize the prevalence and risk factors for the condition. STUDY DESIGN: Patients evaluated in our Lymphedema Program between 2009 and 2016 were reviewed for obese individuals (BMI ≥30 kg/m2) who had lower-extremity lymphatic function evaluated by lymphoscintigraphy. Candidate variables included age, sex, BMI, duration of lymphedema, infection history, and lymphoscintigraphy findings. A possible association between candidate variables and presence of MLL was determined using multivariable logistic regression. Optimal cutoff for BMI in predicting MLL was identified by receiver operating characteristic curve analysis. RESULTS: Eighty-two patients were included in the study population. In patients with MLL (n = 17), all had OIL and none had primary or secondary lymphedema (median BMI 66 kg/m2; interquartile range 62 to 78). Massive localized lymphedema involved the thigh (n = 16; bilateral = 10, unilateral = 6), genitalia (n = 3), and suprapubic area (n = 2). Control patients without MLL (n = 65) had primary (46%), secondary (37%), or obesity-induced (17%) lymphatic dysfunction (median BMI 36 kg/m2; interquartile range 32 to 45). Logistic regression indicated a significant relationship between BMI and MLL condition; patients with a BMI >56 kg/m2 had a 213-times greater odds of MLL developing vs patients with BMI ≤56 kg/m2 (p < 0.0001). Age, sex, duration of obesity, and infection history were not associated with development of MLL (all p > 0.2). CONCLUSIONS: Massive localized lymphedema is a consequence of OIL and affects approximately 60% of obese patients with lower-extremity dysfunction; a BMI >56 kg/m2 significantly increases the risk. Obese individuals should be referred to a bariatric weight-loss center before their BMI reaches a threshold for OIL and MLL to develop.

Up-to-date review of nuclear medicine applications in pediatric thoracic imaging.

Nuclear medicine has an important role in the evaluation of various congenital and acquired pediatric chest diseases. Although the radiopharmaceuticals and nuclear medicine examinations used in children are broadly the same as in adults, there are some key differences in clinical indications and underlying disorders. This article provides the reader with an up-to-date review of practice of nuclear medicine as it relates to the pediatric chest, including its current role and future applications.

Estimation of Split Renal Function With 99mTc-DMSA SPECT: Comparison Between 3D Volumetric Assessment and 2D Coronal Projection Imaging.

OBJECTIVE: Split renal function (SRF) can be estimated with 99mTc-labeled dimercaptosuccinic acid (DMSA) SPECT cortical renal scintigraphy on either 2D projected images or 3D images. The purpose of this study was to determine whether there is a significant difference between SRF values calculated with the 2D method and those calculated with the 3D method. MATERIALS AND METHODS: This retrospective study was performed with 99mTc-DMSA SPECT images of 316 patients (age range, 1-26 years). All images were reconstructed by filtered back projection. An automated computational method was developed to estimate SRF using both 2D projection images and direct 3D images. A paired t test was used to evaluate the difference between SRFs determined with the two methods and the association between the magnitude of the differences and kidney size, patient age, and SRF. RESULTS: There was strong correlation between SRFs estimated with the 2D and 3D methods (r = 0.94, p < 0.001). There was small significant difference (0.14% ± 0.86%, p = 0.003) in SRFs obtained with the two methods. The difference was clinically negligible and independent of renal length (p = 0.698), volume (p = 0.297), and patient age (p = 0.768) but was associated with SRF (p = 0.018). CONCLUSION: For determination of split renal function, 99mTc-DMSA SPECT renal scintigraphy 2D coronal projection images perform as well as and are simpler to analyze than 3D images.

Features and Outcome of Autonomous Thyroid Nodules in Children: 31 Consecutive Patients Seen at a Single Center.

CONTEXT: Most thyroid nodules are benign and their accurate identification can avoid unnecessary procedures. In adult patients, documentation of nodule autonomy is accepted as reassurance of benign histology and as justification to forgo biopsy or thyroidectomy. In contrast, the negative predictive value of nodule autonomy in children is uncertain. Some recent publications recommend surgical resection as initial management, but few address the degree of TSH suppression or the specific scintigraphic criteria used to diagnose autonomy. OBJECTIVE: The objective of the study was to study the presenting features and cancer risk of children with autonomous nodules. DESIGN AND SETTING: Medical records of all 31 children diagnosed with autonomous nodules at our center from 2003 to 2014 were retrospectively reviewed. PATIENTS AND RESULTS: All children met full diagnostic criteria for autonomous nodules, defined by both autonomous 123I uptake into the nodule and the suppression of uptake in the normal thyroid parenchyma on scintigraphy performed during hypothyrotropinemia. The median age of presentation was 15 years (range 3-18 y) with a female to male ratio of 15:1. Fifty-eight percent of patients had solitary nodules and 42% had multiple nodules. The median size of each patient's largest autonomous nodule was 39 mm (range 18-67 mm). Most of the children in this series (68%) had diagnostic biopsies and/or operative pathology of their largest autonomous nodule, which showed benign cytology or histology in all cases. CONCLUSIONS: In this pediatric series, the cancer rate observed in biopsied or resected autonomous nodules was 0%. Whereas larger studies are needed to confirm our findings, these results agree with earlier reports suggesting that thyroid cancer is rare in rigorously defined autonomous nodules and support that conservative management may be offered to selected children who meet strict diagnostic criteria for autonomous nodules, deferring definitive therapies until adulthood when the risks of thyroidectomy and 131I ablation are lower.

Obesity-induced Lymphedema Nonreversible following Massive Weight Loss.

Lymphedema is the progressive enlargement of tissue due to inadequate lymphatic function. Obesity-induced lymphedema of the lower extremities can occur once a patient's body mass index (BMI) exceeds 50. We report our first patient with obesity-induced lower extremity lymphedema who was followed prospectively before and after weight loss. A 46-year-old woman with a BMI of 80 presented to our Lymphedema Program complaining of bilateral lower extremity swelling. Lymphoscintigraphy showed impaired lymphatic drainage of both lower extremities consistent with lymphedema. She was referred to a bariatric surgical weight-loss center and underwent a sleeve gastrectomy. After reaching her new steady-state BMI of 36 eighteen months following her procedure, lymphoscintigraphy showed no improvement in lower extremity lymphatic function. Patients at risk for obesity-induced lymphedema should be counseled that they should seek weight-loss interventions before their BMI reaches 50, a threshold at which point lower extremity lymphedema may occur. Unlike other comorbidities that reverse following massive weight loss, obesity-induced lymphedema may not resolve.

Pediatric Graves' disease: decisions regarding therapy.

PURPOSE OF REVIEW: Graves' disease is the most common cause of hyperthyroidism in the pediatric population. It occurs more often in adolescence and in girls; however, prepubertal children tend to have more severe disease, require longer medical therapy, and have a lower rate of remission as compared with pubertal children. The choice of which of the three therapeutic options to use (medical therapy, radioactive iodine ablation, or surgery) must be individualized. This update will focus on the current diagnostic and treatment modalities available, as well as address the controversy that exists with regards to permanent therapy. RECENT FINDINGS: The diagnosis of Graves' disease is often made clinically. With the development of second-generation and third-generation thyroid-stimulating hormone receptor antibody assays, it can be more reliably confirmed. An improved understanding of the underlying autoimmune process and genetics is underway; however, remission rates in children and adolescents remain low. Because of its ease of administration and long-term follow-up, there is a trend towards permanent therapy with radioactive iodine ablation when remission cannot be achieved with medical therapy. SUMMARY: New genes and susceptibility loci have been identified with the hope of better understanding the refractory nature of Graves' disease. Despite the low rates of remission, permanent therapy with radioactive iodine remains a good option.

Obesity-induced lymphedema: clinical and lymphoscintigraphic features.

UNLABELLED: The purpose of this study was to characterize obesity as a novel cause of lower extremity lymphedema. Fifty-one patients with a body mass index greater than 30 kg/m(2) without any potential cause of lymphedema were evaluated with lymphoscintigraphy. Group 1 patients (n = 33) were at their maximum body mass index; individuals with lymphatic dysfunction had a greater body mass index (72.0 kg/m(2)) compared with subjects with normal function (37.7 kg/m(2)) (p < 0.0001). Body mass index predicted the lymphoscintigram result, which was abnormal if the body mass index was greater than 60 kg/m(2) and normal if it was less than 50 kg/m(2). Group 2 patients (n = 18) had lost weight and were not at their maximum body mass index: patients who reduced their body mass index from greater than 60 kg/m to less than 50 kg/m(2) had normal (n = 4) or abnormal (n = 3) lymphatic function. Patients with obesity-induced lymphedema, or who were at risk for the condition, were referred to a surgical weight loss center. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.