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This study tested the hypotheses that 1) changes in mid-treatment fluorodeoxyglucose (FDG)-positron emission tomography (PET) parameters are predictive of overall survival (OS) and 2) mid-treatment FDG-PET-adapted treatment has the potential to improve survival in patients with non-small cell lung cancer (NSCLC).Patients with stage I-III NSCLC requiring daily fractionated radiation were eligible. FDG-PET-CT scans were obtained prior to and mid-treatment with radiotherapy at 40-50 Gy. The normalized maximum standardized uptake value (NSUVmax), normalized mean SUV (NSUVmean), PET-metabolic tumor volume (MTV), total lesion glycolysis (TLG), and computed tomography-based gross tumor volume (CT-GTV) were consistently measured for all patients. The primary study endpoint was OS.The study is comprised of 102 patients who received 3-dimensional conformal radiotherapy, among whom 30 patients who received mid-treatment PET-adapted dose escalation radiotherapy. All PET-CT parameters decreased significantly (P 0.001) mid-treatment, with greater reductions in FDG-volumetric parameters compared to FDG-activity factors. Mid-treatment changes in MTV (P = 0.053) and TLG (P = 0.021) were associated with OS, while changes in NSUVmax, NSUVmean, and CT-GTV were not (all Ps0.1). Patients receiving conventional radiation (60-70 Gy) with MTV reductions greater than the mean had a median survival of 14 months, compared to those with MTV reductions less than the mean who had a median survival of 22 months. By contrast, patients receiving mid-treatment PET-adapted radiation with MTV reductions greater than the mean had a median survival of 33 months, compared to those with MTV reductions less than the mean who had a median survival of 19 months. Overall, PET-adapted treatment resulted in a 19% better 5-year survival than conventional radiation.Changes in mid-treatment PET-volumetric parameters were significantly associated with survival in NSCLC. A greater reduction in the mid-treatment MTV was associated with worse survival in patients treated with standard radiation, but with better survival in patients who received mid-treatment PET-adapted treatment.

Sarcoidosis and chronic beryllium disease (CBD) are phenocopies, however the latter one has a clear trigger factor that is beryllium exposure. This study analyses single nucleotide polymorphisms (SNPs) in a large cohort for beryllium-exposed persons. SNPs were chosen for their relevance in sarcoidosis. Even though one of largest cohorts of beryllium-exposed persons was analysed, no statistically relevant association between any SNP and CBD could be verified. Notably, some SNPs exhibit inverse OR for beryllium sensitization and CBD with nominally statistical significance, which allows hypothesizing about pathophysiological role of genes for the disease triggering and development.

Objective To evaluate the success rate of therapeutic administration of a single calculated 131I activity for eliminating hyperthyroidism due to Graves’ disease. Methods and materials Patients with Graves’ hyperthyroidism underwent pinhole thyroid imaging, 24-h radioactive iodine uptake (RAIU) measurements and clinical examination and received a calculated 131I activity of 0.2 mCi per estimated gram of thyroid tissue, adjusted for the 24-h RAIU. The goal of RAI treatment was to achieve hypothyroidism within 3–6 months of 131I administration. Response to RAI therapy was assessed at 7 weeks and 3 months by clinical and biochemical follow-up. Results The study included 316 hyperthyroid patients with Graves’ disease (F238:M78, mean age 42.1 ± 16 y, 4–94). 179 patients (56.6%) had no prior therapeutic intervention (treatment-naive patients), whereas 6 patients had prior thyroid surgery, and 131 (41.5%) had been treated with anti-thyroid medications. The mean estimated thyroid gland size was 50.2 g ± 18, range 15–100. Mean RAIU was 0.57 ± 0.17 (normal 0.07–0.30). RAI doses ranged from 5 to 70 mCi (mean dose = 18.1 mCi). Successful treatment of hyperthyroidism at our institution was obtained after a single therapeutic 131-I activity administration in 295 of 316 (93.3%) patients. Multivariate logistic regression analysis demonstrated that failure of 131I therapy was associated with previous PTU therapy (p 90%) of patients, adjusting for the thyroid size and 24 h uptake measurement.

The extent of whether staging by fluorodeoxyglucose positron-emission tomography (PET) impacts outcomes in American Veterans with stage I-III non–small-cell lung cancer (NSCLC) is unknown. We investigated impact of fluorodeoxyglucose PET staging and age-adjusted comorbidities (AACs) on management and survival of NSCLC in this group. We performed a retrospective review to identify with NSCLC who underwent initial PET scan and received care at the Ann Arbor Veterans Hospital between 2005 and 2010. Survival outcomes were estimated by Kaplan-Meier methods, quantile regressions, and Cox proportional hazards models, after accounting for age at diagnosis, sex, AAC, and initial treatment. The number of PET scans increased from 0 in 2005 to 66 in 2010. There were 170 men, 4 women, median age 64 years. Median AAC score was 4. In CS I (n=54), initial PET upstaged 5 patients. Median survival for no change in PET stage was 27.43 versus 67 months for upstaged patients (P=0.034). For CS II (n=15), initial PET scan upstaged 1 patient. Median survival for no change in PET stage was 16.53 versus 2.8 months for upstaged patient (P=0.335). For CS III (n=104), PET scan upstaged 20 patients. Median survival for no change in PET stage was 13.3 versus 3.8 months for upstaged patients (P=0.016). PET scans resulted in upstaging in 15% in CS I-III NSCLC. AAC scores dictated therapy decisions and outcomes more than PET staging. Veterans had lower 5-year survival rates (26.3%, 15.8%/13.4%) compared with 53% and 27% in age/sex/time-period matched SEER data for stage I-II/III NSCLC.

The etiology of sarcoidosis is unknown, but microbial agents are suspected as triggers.We sought to identify bacterial, fungal, or viral lineages in specimens from patients with sarcoidosis enriched relative to control subjects using metagenomic DNA sequencing. Because DNA from environmental contamination contributes disproportionately to samples with low authentic microbial content, we developed improved methods for filtering environmental contamination.We analyzed specimens from subjects with sarcoidosis (n = 93), control subjects without sarcoidosis (n = 72), and various environmental controls (n = 150). Sarcoidosis specimens consisted of two independent sets of formalin-fixed, paraffin-embedded lymph node biopsies, BAL, Kveim reagent, and fresh granulomatous spleen from a patient with sarcoidosis. All specimens were analyzed by bacterial 16S and fungal internal transcribed spacer ribosomal RNA gene sequencing. In addition, BAL was analyzed by shotgun sequencing of fractions enriched for viral particles, and Kveim and spleen were subjected to whole-genome shotgun sequencing.In one tissue set, fungi in the Cladosporiaceae family were enriched in sarcoidosis compared with nonsarcoidosis tissues; in the other tissue set, we detected enrichment of several bacterial lineages in sarcoidosis but not Cladosporiaceae. BAL showed limited enrichment of Aspergillus fungi. Several microbial lineages were detected in Kveim and spleen, including Cladosporium. No microbial lineage was enriched in more than one sample type after correction for multiple comparisons.Metagenomic sequencing revealed enrichment of microbes in single types of sarcoidosis samples but limited concordance across sample types. Statistical analysis accounting for environmental contamination was essential to avoiding false positives.

Objective: Postpartum thyroiditis presents as thyrotoxicosis from autoimmune thyroid inflammation that causes release of iodothyronines and diffuse, decreased thyroid uptake of both radioactive iodine and 99mTc-pertechnetate. Thyroiditis with focal “cold” thyroid nodule on thyroid scintigraphy has been previously described and attributed to localized inflammation.Methods: We report a patient diagnosed with postpartum thyroiditis, in whom an apparently “hot” nodule on initial thyroid pinhole scintigraphy was later noted to be “cold” at follow-up imaging.Results: Thyroid nodularity co-existing with subacute thyroiditis usually presents as focal “cold” nodules, attributed to localized inflammation in the thyroid. The diagnosis of postpartum thyroiditis in our patient was made more challenging due to the presence of a thyroid nodule with an evolving imaging appearance over time. This led to a potential for misdiagnosis of this “hot” nodule dependent on the timing of having the thyroscintigram performed early in the disease course. We hypothesized that the overactive focus of uptake was due to sparing of a pre-existing colloid nodule by the inflammatory process which later became “cold” in the recovery phase.Conclusion: The presence of co-existing thyroiditis and thyroid nodules, both common entities, may cause diagnostic difficulty on thyroid scintigraphy due to dynamic, temporal changes in imaging appearance and the variable findings reported in the literature. Clinical surveillance and performing repeat thyroid imaging will allow correct diagnosis and appropriate management of these challenging cases.Abbreviation: RAIU radioactive iodine uptake

Adrenal lesions are routinely encountered incidentally in clinical practice. Although most of these lesions are benign, malignancy needs to be excluded. Therefore, the initial clinical workup is to exclude aggressive characteristics suggesting malignancy and to identify characteristics predictive of the most common benign lesion, an adrenal adenoma. Predicting a benign adenoma using a variety of imaging modalities has been widely studied using unenhanced computed tomography (CT), contrast enhanced CT, and magnetic resonance (MR) imaging. This review article describes the currently used imaging protocols and clinical interpretation criteria of common adrenal lesions. An adenoma can be predicted if a homogenous soft tissue adrenal mass demonstrates low attenuation (upper threshold value of 10 Hounsfield Units) on unenhanced CT, demonstrates an absolute enhancement washout of ≥ 60% and/or relative enhancement washout of ≥ 40% on adrenal washout contrast enhanced CT, or demonstrates signal loss in opposed-phased MR imaging. If an adrenal adenoma cannot be predicted based upon these criteria, the lesion should be evaluated for other imaging characteristics that suggest a specific pathology, such as an adrenal cyst or myelolipoma. Although nonspecific and with limitations, 18F-fluorodeoxyglucose (FDG) PET/CT has a potential role for differentiating benign from malignant lesions based upon the amount of radiopharmaceutical uptake with malignant lesions generally having greater uptake. If clinical and/or hormonal screening suggests a pheochromocytoma, consideration can be given to 18F-dihydroxyphenylalanine (DOPA) or 123I-metaiodobenzylguanidine (MIBG) in addition to CT and MR. Finally, this review proposes a diagnostic work-up strategy for routine use in clinical practice.

Purpose: Hyperglycemia affects FDG uptake in the brain, potentially emulating Alzheimer’s disease in normal individuals. This study investigates global and regional cerebral FDG uptake as a function of plasma glucose in a cohort of patients. Methods: 120 consecutive male patients with FDG PET/CT for initial oncologic staging (July–Dec 2015) were reviewed. Patients with dementia, cerebrovascular accident, structural brain lesion, prior oncology treatment or high metabolic tumor burden (recently shown affecting brain FDG uptake) were excluded. 53 (24 nondiabetic) eligible patients (age 65.7 ± 2.8 mean ± SE) were analyzed with parametric computer software, MIMneuro™. Regional Z-scores were evaluated as a function of plasma glucose and age using multi variable linear mixed effects models with false discovery analysis adjusting for multiple comparisons. If the regression slope was significantly (p

Lingual thyroid is a rare abnormality of thyroid development that is usually treated conservatively with levothyroxine replacement. Rarely, it becomes large enough to cause obstructive symptoms in the oral cavity, requiring definitive treatment.This study reports on three patients with lingual thyroid treated with radioactive iodine-131 ((131)I) with successful radioablation of their ectopic thyroid tissues. Measurement of 24-hour radioactive iodine uptake within thyroidal tissues and hybrid single-photon emission computed tomography/computed tomography imaging using either iodine-123 or technetium-99m pertechnetate scans were performed in all patients demonstrating the location and size of lingual thyroid and absence of an orthotopic thyroid gland.The aim of this study was to describe nonsurgical management of obstructive lingual thyroid tissue with (131)I therapy for lingual thyroid radioablation. Patients were prepared with a low-iodine diet and levothyroxine withdrawal prior to radioablation for optimizing (131)I uptake in ectopic thyroid tissues. Hybrid single-photon emission computed tomography/computed tomography measurement of anatomic size of lingual thyroid tissue and radioactive iodine uptake guided the selection of therapeutic doses, resulting in administration of 10.7, 17.5, and 15.4 mCi of (131)I, respectively. There were no post-therapy complications, and clinical follow-up demonstrated resolution of obstructive oropharyngeal symptoms.Ectopic lingual thyroid tissue is rarely associated with obstructive oropharyngeal symptoms due to progressive enlargement. Radioiodine therapy with (131)I is an effective treatment modality for ablation of ectopic thyroid tissue as an alternative to surgery.

Painful osseous metastasis resulting from castration-resistant prostate carcinoma is a common clinical problem. Historically, nuclear medicine offered several palliative beta-emitting radiopharmaceuticals targeting the skeleton with the goal of decreasing pain. However, these have largely been replaced by the alpha-emitting agent 223radium (Ra). 223Ra received Food and Drug Administration approval in 2013 for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases without visceral metastases. 223Ra offers an improved therapeutic profile due to its alpha-particle emissions resulting in a relatively higher linear energy transfer and lower particle range compared with beta-emitters. 223Ra also has demonstrated to increase overall survival in patients and to delay adverse skeletal events. Running a successful clinical nuclear therapy program with Ra requires a multidisciplinary team approach and this article suggests an implementation strategy from the authors' institution. Potential new nuclear radiopharmaceuticals still under investigation offering the future possibility of radioligand therapy are also discussed briefly.

In addition to nuclear cardiac and breast imaging, Tc-sestamibi scintigraphy is often used to localize parathyroid adenomas. F- fluorodeoxyglucose (FDG) PET is heavily utilized in oncology, although its use in identifying parathyroid adenomas is limited. We describe a case of a 57-year-old woman who underwent parathyroid scintigraphy and F-FDG PET/CT in the same week due to hyperparathyroidism and an enlarging breast mass, respectively. A right paratracheal mediastinal mass that otherwise would be suspicious for nodal metastases by CT alone was correctly identified to be an ectopic parathyroid adenoma using a combination of the nuclear medicine studies performed.

Purpose This study tested the ability of a multibreath hyperpolarized HP 3He MRI protocol to increase the accuracy of regional alveolar oxygen tension (PAO2) measurements by lessening the influence of gas-flow artifacts. Conventional single-breath PAO2 measurement has been susceptible to error induced by intervoxel gas flow, particularly when used to study subjects with moderate-to-severe chronic obstructive pulmonary disease (COPD). Methods Both single-breath and multibreath PAO2 imaging schemes were implemented in seven human subjects (one healthy, three asymptomatic smokers, and three COPD). The number and location of voxels with nonphysiologic PAO2 values generated by intervoxel gas flow were compared between the two protocols. Results The multibreath scheme resulted in a significantly lower total percentage of nonphysiologic PAO2 values (6.0%) than the single-breath scheme (13.7%) (P = 0.006). PAO2 maps showed several patterns of gas-flow artifacts that were present in the single-breath protocol but mitigated by the multibreath approach. Multibreath imaging also allowed for the analysis of slow-filling areas that presented no signal after a single breath. Conclusion A multibreath approach enhances the accuracy and completeness of noninvasive PAO2 measurement by significantly lessening the proportion of nonphysiologic values generated by intervoxel gas flow. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

To reconstruct reliable nuclear medicine-related occupational radiation doses or doses received as patients from radiopharmaceuticals over the last five decades, the authors assessed which radiopharmaceuticals were used in different time periods, their relative frequency of use, and typical values of the administered activity. This paper presents data on the changing patterns of clinical use of radiopharmaceuticals and documents the range of activity administered to adult patients undergoing diagnostic nuclear medicine procedures in the U.S. between 1960 and 2010. Data are presented for 15 diagnostic imaging procedures that include thyroid scan and thyroid uptake; brain scan; brain blood flow; lung perfusion and ventilation; bone, liver, hepatobiliary, bone marrow, pancreas, and kidney scans; cardiac imaging procedures; tumor localization studies; localization of gastrointestinal bleeding; and non-imaging studies of blood volume and iron metabolism. Data on the relative use of radiopharmaceuticals were collected using key informant interviews and comprehensive literature reviews of typical administered activities of these diagnostic nuclear medicine studies. Responses of key informants on relative use of radiopharmaceuticals are in agreement with published literature. Results of this study will be used for retrospective reconstruction of occupational and personal medical radiation doses from diagnostic radiopharmaceuticals to members of the U.S. radiologic technologists' cohort and in reconstructing radiation doses from occupational or patient radiation exposures to other U.S. workers or patient populations.

The aim of the study was to determine the diagnostic utility of parathyroid scintigraphy with technetium-99m (99mTc)-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) for localization of parathyroid adenoma.We performed a systematic search of medical databases PubMed and Medline/OVID for literature on 99mTc-sestamibi SPECT/CT parathyroid scintigraphy, using the search terms hyperparathyroidism, parathyroid adenoma/hyperplasia, SPECT/CT, and SPECT-CT. Citations for 981 articles and 128 abstracts of full articles were reviewed by two coauthors for relevance. Twenty-four peer-reviewed studies on SPECT/CT parathyroid scintigraphy qualified for inclusion. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess study quality. Meta-analytical techniques were used to obtain pooled estimates of the parathyroid adenoma localization rate using a random-effects model.A total of 24 studies published between January 2003 and March 2014 with 1276 patients (334 men, 762 women, and 180 of unspecified sex) met the inclusion criteria. Data on the test performance of dual-phase 99mTc-sestamibi SPECT/CT showed an estimated pooled sensitivity (per-patient analysis) of 0.86 [confidence interval (CI) 0.81-0.90]. Sensitivity of SPECT/CT was superior to that of SPECT (0.74; CI 0.66-0.82) and planar (0.70; CI 0.61-0.80) techniques. Heterogeneity was present in the reported literature (I2=80.3%). The rate of ectopic parathyroid adenomas ranged between 4 and 20% and SPECT/CT was superior to SPECT and planar imaging for localization of ectopic sites.Utilization of SPECT/CT fusion imaging for 99mTc-sestamibi parathyroid scintigraphy improves the test performance compared with planar and SPECT imaging; it assists preoperative planning for a minimally invasive surgical approach for the neck and is of value in subgroups with ectopic glands or coexisting nodular thyroid disease.

Background\ud Despite the relationship between idiopathic pulmonary fibrosis (IPF) and advancing age, little is known about the epidemiology of interstitial lung disease (ILD) in the elderly. We describe the diagnoses, clinical characteristics, and outcomes of patients who were elderly at the time of ILD diagnosis.\ud \ud Methods\ud Among subjects from a prospective cohort study of ILD, elderly was defined as age ≥ 70 years. Diagnoses were derived from a multidisciplinary review. Differences between elderly and nonelderly groups were determined using the χ2 test and analysis of variance.\ud \ud Results\ud Of the 327 subjects enrolled, 80 (24%) were elderly. The majority of elderly subjects were white men. The most common diagnoses were unclassifiable ILD (45%), IPF (34%), connective tissue disease (CTD)-ILD (11%), and hypersensitivity pneumonitis (8%). Most elderly subjects (74%) with unclassifiable ILD had an imaging pattern inconsistent with usual interstitial pneumonia (UIP). There were no significant differences in pulmonary function or 3-year mortality between nonelderly and elderly subjects combined or in a subgroup analysis of those with IPF.\ud \ud Conclusions\ud Although IPF was the single most common diagnosis, the majority of elderly subjects had non-IPF ILD. Our findings highlight the need for every patient with new-onset ILD, regardless of age, to be surveyed for exposures and findings of CTD. Unclassifiable ILD was common among the elderly, but for most, the radiographic pattern was inconsistent with UIP. Although the effect of ILD may be more pronounced in the elderly due to reduced global functionality, ILD was not more severe or aggressive in this group.

The purpose of this study was to systematically review the utility of single-photon emission tomography–computed tomography (SPET–CT) fusion imaging in the investigation of thyroid cancer. We performed a systematic search of the world literature on radionuclide SPET–CT imaging of thyroid cancer using the medical databases Medline (OVID) and PubMed. The following search terms were used to identify relevant studies: (a) thyroid, combined with (b) SPECT/CT or SPECT–CT or SPET/CT or SPET–CT. The electronic searches returned citations for 1,189 potentially eligible articles and 98 abstracts were reviewed for relevance by two co-authors. Thirty-one peer-reviewed full articles reporting the utility, value and diagnostic performance of radioiodine SPET–CT for the imaging of well-differentiated thyroid cancer were selected. The quality of these studies was assessed using the quality assessment of diagnostic accuracy studies-2 tool. As there was heterogeneity in the studies, a systematic review analysis was conducted as our chosen research synthesis method. A total of 31 studies published between 2003 and 2014 report the utility of radioiodine SPET–CT. These studies uniformly found incremental diagnostic value of I-123 and I-131 SPET–CT over SPET and/or planar imaging. SPET–CT allows accurate characterization of radioiodine uptake in the neck and at distant sites, clarifies equivocal foci of radioactivity, improves specificity for disease, and evaluates benign physiological etiologies. Additional pilot uses of SPET–CT have been reported, e.g., for thyroid nodule evaluation, medullary thyroid cancer work-up, and investigation of lingual thyroid. Radioiodine SPET–CT fusion imaging of thyroid cancer has incremental utility, improving image interpretation as compared to planar and SPET imaging. It is likely to see more widespread application in the future.

Endocrine tumors are hormonally active benign or malignant neoplasms arising within endocrine organs or from specialized cells of the amine precursor uptake and decarboxylation system. The detection rate of these tumors is increasing as a result of sensitive biochemical tests and high-resolution diagnostic imaging. Medical imaging has become a key component in the diagnosis and staging of endocrine malignancies; however, despite the impressive advances in computed tomography (CT) and MRI, detection of small primary tumors and metastases continues to be a challenge. Functional imaging techniques use radiopharmaceuticals targeted at unique tumor cellular processes in order to provide sensitive and highly specific whole-body imaging. Functional imaging allows prediction of the efficacy of radionuclide or receptor-based therapies and surveillance after therapy. Advances in imaging have not been limited to radiopharmaceuticals. Hybrid scanner technology in the form of PET/CT and single photon emission computed tomography (SPECT)/CT, designed to combine functional images with anatomic maps, has further improved the diagnostic accuracy. High-resolution hybrid imaging when deployed with novel PET and SPECT radiopharmaceuticals has the potential to dramatically change, individualize, and optimize imaging plans based on the histological grade, degree of differentiation, and genetic profile of each patient's endocrine neoplasm.

Sites of infection and inflammation can be misleading in oncology PET/CT imaging because these areas commonly show 18F-FDG activity. Caution in the interpretation must be taken to avoid the misdiagnosis of malignancy. Utilization of both CT findings as well as patient history can help differentiate benign infectious and inflammatory processes from malignancy, although occasionally additional work-up may be required. This article discusses the mechanism of 18F-FDG uptake in infection and inflammation with illustrative examples.

Purpose To present a method for simultaneous acquisition of alveolar oxygen tension (PAO2), specific ventilation (SV), and apparent diffusion coefficient (ADC) of hyperpolarized (HP) gas in the human lung, allowing reinterpretation of the PAO2 and SV maps to produce a map of oxygen uptake (R). Method An imaging scheme was designed with a series of identical normoxic HP gas wash-in breaths to measure ADC, SV, PAO2, and R in less than 2 min. Signal dynamics were fit to an iterative recursive model that regionally solved for these parameters. This measurement was successfully performed in 12 subjects classified in three healthy, smoker, and chronic obstructive pulmonary disease (COPD) cohorts. Results The overall whole lung ADC, SV, PAO2, and R in healthy, smoker, and COPD subjects was 0.20 ± 0.03 cm2/s, 0.39 ± 0.06,113 ± 2 Torr, and 1.55 ± 0.35 Torr/s, respectively, in healthy subjects; 0.21 ± 0.03 cm2/s, 0.33 ± 0.06, 115.9 ± 4 Torr, and 0.97 ± 0.2 Torr/s, respectively, in smokers; and 0.25 ± 0.06 cm2/s, 0.23 ± 0.08, 114.8 ± 6.0Torr, and 0.94 ± 0.12 Torr/s, respectively, in subjects with COPD. Hetrogeneity of SV, PAO2, and R were indicators of both smoking-related changes and disease, and the severity of the disease correlated with the degree of this heterogeneity. Subjects with symptoms showed reduced oxygen uptake and specific ventilation. Conclusion High-resolution, nearly coregistered and quantitative measures of lung function and structure were obtained with less than 1 L of HP gas. This hybrid multibreath technique produced measures of lung function that revealed clear differences among the cohorts and subjects and were confirmed by correlations with global lung measurements. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine

Adrenocortical cancer (ACC) is an uncommon primary neoplasm of the adrenal cortex with dismal prognosis. It often presents with symptoms and signs of adrenal cortical hormone hypersecretion and abdominal mass effect or is incidentally detected as an adrenal mass on imaging performed for other indications. Endocrine evaluation, comprehensive staging, and meticulous resection are crucial to ensure the best possible outcome. Despite extensive initial surgical resection, local and distant metastases are not uncommon with disappointing 5-year survival, although progress is being made at high-volume centers. Accurate restaging of recurrent disease is important to guide further management. Mitotane, external beam radiation and chemotherapy, and newer anticancer systemic treatments are used as adjunctives for inoperable disease and distant metastases. Contrast-enhanced CT and MRI are first-line imaging modalities for evaluation of ACC to characterize adrenal masses and to determine tumor resectability. Emerging literature supports F-FDG PET/CT use to determine the malignant potential of adrenal masses. In patients with a diagnosis of ACC, FDG PET/CT is sensitive for detecting metastatic disease, and its tumor accumulation has been correlated to pathology, Weiss scores, and prognosis. Metomidate, labeled with C for PET or with I for SPECT/CT, allows characterization of an adrenal mass as being of adrenocortical origin with high specificity. Taking advantage of its adrenocortical avidity, metomidate has been labeled with I for radionuclide therapy in a subset of ACC. In this review, we describe how nuclear medicine imaging, and specifically PET, can assist surgical management of ACC.

The whole-body 131-I scan remains an important component of the treatment of postthyroidectomy patients with well-differentiated thyroid cancer. Because normal thyroid tissue remnants and residual or metastatic foci of well-differentiated thyroid cancer have the unique ability to concentrate, organify, and store 131-I, the whole-body scan provides a functional map of tissues that can be definitively treated with therapeutic doses of 131-I. Despite the high sensitivity and specificity of radioiodine imaging, the whole-body scan may also depict concentrations of 131-I from a wide variety of other “nonthyroid” etiologies. In this chapter, we update our article from the Seminars of Nuclear Medicine (modified with permission. Shapiro B, Rufini V, Jarwan A, et al. Seminars in Nuclear Medicine 30:115–132, 2000.) in 2000 that described the pathophysiological classification of artifacts, anatomical and physiological variants, and nonthyroidal diseases responsible for false-positive whole-body scans in postthyroidectomy patients with thyroid cancer. These confounding imaging findings include ectopic foci of normal thyroid tissue, nonthyroidal physiologic uptake (e.g., choroid plexus, salivary glands, gastric mucosa, urinary tract), contamination by physiological secretions, ectopic gastric mucosa and other anatomic gastrointestinal abnormalities, urinary tract abnormalities, mammary abnormalities, serous cavities and cysts, inflammation and infection, nonthyroidal neoplasms, and other unexplained causes.

This study aimed to (1) examine changes in dyspnea, global pulmonary function test (PFT) results, and functional activity on ventilation (V)/perfusion (Q) single-photon emission computerized tomography (SPECT) scans during the course of radiation (RT), and (2) factors associated with the changes in patients with non-small-cell lung cancer (NSCLC).Fifty-six stage I to III NSCLC patients treated with definitive RT with or without chemotherapy were enrolled prospectively. Dyspnea was graded according to Common Terminology Criteria for Adverse Events version 3.0 prior to and weekly during RT. V/Q SPECT-computed tomography (CT) and PFTs were performed prior to and during RT at approximately 45 Gy. Functions of V and Q activities were assessed using a semiquantitative scoring of SPECT images.Breathing improved significantly at the third week (mean dyspnea grade, 0.8 vs. 0.6; paired t-test p = 0.011) and worsened during the later course of RT (p0.05). Global PFT results did not change significantly, while regional lung function on V/Q SPECT improved significantly after ∼45 Gy. The V defect score (DS) was 4.9 pre-RT versus 4.3 during RT (p = 0.01); Q DS was 4.3 pre-RT versus 4.0 during RT (p0.01). Improvements in V and Q functions were seen primarily in the ipsilateral lung (V DS, 1.9 pre-RT versus 1.4 during RT, p 0.01; Q DS, 1.7 pre-RT versus 1.5 during RT, p0.01). Baseline primary tumor volume was significantly correlated with pre-RT V/Q DS (p0.01). Patients with central lung tumors had greater interval changes in V and Q than those with more peripheral tumors (p0.05 for both V and Q DS).Regional ventilation and perfusion improved during RT at 45 Gy. This suggests that adaptive planning based on V/Q SPECT during RT may allow sparing of functionally recoverable lung tissue.

Introduction: Perfusion (Q) single photon emission computed tomography (SPECT) has been used to divert dose away from higher-functioning lung during radiation therapy (RT) planning. This study aimed to (1) study regional lung function through coregistered pulmonary ventilation/perfusion (V/Q)-SPECT-CT and (2) classify these defects for its potential value in radiation planning in patients with non-small cell lung cancer (NSCLC). Methods: Patients with stages I to III NSCLC requiring radiation-based therapy were eligible for this prospective study. V/Q-SPECT performed within 2 weeks before the start of radiation was interpreted by nuclear medicine physicians and then measured by a semiquantitative score. The potential mechanism of V and Q defects was analyzed; the potential impact of V/Q-SPECT over Q-SPECT alone was completed through classified applications (high-dose RT versus RT avoidance) during planning. Results: Images of 51 consecutive patients were analyzed. The V and Q defects were matched, reverse mismatched (V defect > Q defect), and mismatched (Q defect > V defect) in 61, 31, and 8% of patients, respectively. Tumor was the leading cause of the defects of ipsilateral lung in 73% of patients. The defect scores of the ipsilateral lung were greater in patients with central primaries than those with peripheral primaries for both V-SPECT (2.3 ± 1.1 versus 1.5 ± 0.8, p = 0.017) and Q-SPECT (2.2 ± 0.8 versus 1.4 ± 0.6, p = 0.000). The patients with chronic obstructive pulmonary disease had greater defect scores in contralateral lung for both V-SPECT (1.5 ± 0.7 versus 1.0 ± 0.8, p = 0.006) and Q-SPECT (1.4 ± 0.6 versus 1.0 ± 0.4, p = 0.010). On assessing the potential value of SPECT on RT plan, 39% of patients could have their RT plan when applying V/Q-SPECT rather than Q-SPECT alone. Conclusions: V/Q-SPECT provides a more comprehensive functional assessment, may provide additional value over Q-SPECT alone in assessing local pulmonary function, and guide RT plan decisions in patients with NSCLC.

Rationale and Objectives The use of hyperpolarized 3 He magnetic resonance imaging as a quantitative lung imaging tool has progressed rapidly in the past decade, mostly in the assessment of the airway diseases chronic obstructive pulmonary disease and asthma. This technique has shown potential to assess both structural and functional information in healthy and diseased lungs. In this study, the regional measurements of structure and function were applied to a bleomycin rat model of interstitial lung disease. Materials and Methods Male Sprague-Dawley rats (weight, 300–350 g) were administered intratracheal bleomycin. After 3 weeks, apparent diffusion coefficient and fractional ventilation were measured by 3 He magnetic resonance imaging and pulmonary function testing using a rodent-specific plethysmography chamber. Sensitized and healthy animals were then compared using threshold analysis to assess the potential sensitivity of these techniques to pulmonary abnormalities. Results No significant changes were observed in total lung volume and compliance between the two groups. Airway resistance elevated and forced expiratory volume significantly declined in the 3-week bleomycin rats, and fractional ventilation was significantly decreased compared to control animals ( P 3 He showed a smaller change but still a significant decrease in 3-week bleomycin animals ( P Conclusions Preliminary results suggest that quantitative 3 He magnetic resonance imaging can be a sensitive and noninvasive tool to assess changes in an animal interstitial lung disease model. This technique may be useful for longitudinal animal studies and also in the investigation of human interstitial lung diseases.

Background Appropriate surgical approach to diseases of the adrenal requires a diagnosis sufficient to determine the biochemical status of adrenal dysfunction and anatomic evaluation sufficient to differentiate unilateral from bilateral disease, intra-adrenal from extra-adrenal neoplasm, adrenal tumor recurrence or adrenal metastases. High resolution computed tomography (CT) and magnetic resonance have been the primary imaging modalities for the evaluation of anatomy, while scintigraphic studies have played a secondary role in diagnosis. The recent availability of functional imaging provided by positron emission tomography (PET) with radiopharmaceuticals designed to depict substrate precursor uptake, cellular metabolism or receptor binding in neoplasms and CT as a single modality, hybrid PET/CT, to directly correlate function and anatomy has had a significant impact upon the diagnostic and therapeutic approach to many cancers and has been applied to adrenal disease with some early success that we describe in this review. Methods In addition to the authors' experience, a search of Medline and PubMed databases was performed using search terms: ‘adrenal scintigraphy’, ‘positron tomography’, ‘computed tomography’, ‘adrenal surgery’, ‘adrenal mass’, ‘ 18 F-fluorodeoxyglucose’, ‘adrenal carcinoma’, ‘adrenal medulla’ and ‘pheochromocytoma’. Conclusions Present PET radiopharmaceuticals and their use in hybrid PET/CT have demonstrated efficacy in the preoperative and follow-up evaluation of neoplasms of the adrenal cortex and medulla that hopefully will continue to improve with the development of newer tracers that continue to exploit unusual characteristics of the adrenals.

The incidental discovery of adrenal masses during modern diagnostic imaging is a common occurrence. These masses form part of a long differential diagnostic list; most often, they are benign adrenal adenomas, but their discovery requires a clinical evaluation that is sufficiently broad to exclude clinically silent endocrine disease, metastases to the adrenal gland in patients with suspected or known malignancies, and rare adrenocortical carcinomas. CT, MRI and nuclear medicine approaches have all been used to evaluate incidentally discovered adrenal masses. Each technology provides information that contributes to the noninvasive characterization of the majority of these neoplasms. Understanding of the modalities used to assess an unanticipated adrenal mass allows for more rapid diagnosis and cost avoidance in a condition that has been referred to as a 'disease' of modern imaging technology.

Purpose To quantify changes in fluorodeoxyglucose (FDG)-avid tumor volume on positron emission tomography/computed tomography (PET/CT) during the course of radiation therapy and examine its potential use in adaptive radiotherapy for tumor dose escalation or normal tissue sparing in patients with non–small-cell lung cancer (NSCLC). Methods and Materials As part of a pilot study, patients with Stage I–III NSCLC underwent FDG-PET/CT before radiotherapy (RT) and in mid-RT (after 40–50 Gy). Gross tumor volumes were contoured on CT and PET scans obtained before and during RT. Three-dimensional conformal RT plans were generated for each patient, first using only pretreatment CT scans. Mid-RT PET volumes were then used to design boost fields. Results Fourteen patients with FDG-avid tumors were assessed. Two patients had a complete metabolic response, and 2 patients had slightly increased FDG uptake in the adjacent lung tissue. Mid-RT PET scans were useful in the 10 remaining patients. Mean decreases in CT and PET tumor volumes were 26% (range, +15% to −75%) and 44% (range, +10% to −100%), respectively. Designing boosts based on mid-RT PET allowed for a meaningful dose escalation of 30–102 Gy (mean, 58 Gy) or a reduction in normal tissue complication probability (NTCP) of 0.4–3% (mean, 2%) in 5 of 6 patients with smaller yet residual tumor volumes. Conclusions Tumor metabolic activity and volume can change significantly after 40–50 Gy of RT. Using mid-RT PET volumes, tumor dose can be significantly escalated or NTCP reduced. Clinical studies evaluating patient outcome after PET-based adaptive RT are ongoing.

The inappropriate expression of the c-MET cell surface receptor in many human solid tumors necessitates the development of companion diagnostics to identify those patients who could benefit from c-MET targeted therapies. Tumor tissues are formalin-fixed and paraffin embedded (FFPE) for histopathological evaluation, making the development of an antibody against c-MET that accurately and reproducibly detects the protein in FFPE samples an urgent need. We have developed a monoclonal antibody, designated MET4, from a panel of MET-avid monoclonal antibodies, based on its specific staining pattern in FFPE preparations of normal human prostate tissues. The accuracy of MET4 immunohistochemistry (MET4-IHC) was assessed by comparing MET4-IHC in FFPE cell pellets with immunoblotting analysis. The technical reproducibility of MET4-IHC possessed a percentage coefficient of variability (%CV) of 6.25% in intra-assay and inter-assay testing. Comparison with other commercial c-MET antibody detection reagents demonstrated equal specificity and increased sensitivity for c-MET detection in prostate tissues. In two cohorts of ovarian cancers and gliomas, MET4 reacted with ovarian cancers of all histological subtypes (strong staining in 25%) and with 63% of gliomas. In addition, MET4 bound c-Met on the surfaces of cultured human cancer cells and tumor xenografts. In summary, the MET4 monoclonal antibody accurately and reproducibly measures c-MET expression by IHC in FFPE tissues and can be used for molecular imaging in-vivo. These properties encourage further development of MET4 as a multipurpose molecular diagnostics reagent to help to guide appropriate selection of patients being considered for treatment with c-MET-antagonistic drugs.

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating in the parafollicular cells (C cells) of the thyroid and secretes both calcitonin and carcino-embryonic antigen (CEA). Genetic and biochemical testing allow early pre-clinical identification of familial forms. Sporadic MTC usually presents as a solitary thyroid nodule; the diagnosis can be made preoperatively by fine-needle aspiration or by calcitonin assay, though it is usually established at the time of surgery. In the diagnostic assessment of MTC, nuclear medicine imaging provides its contribution mainly in the post-operative work-up to detect residual/recurrent tumor. For such purpose a number of radiopharmaceuticals, which take advantage of the specific expression of receptors (the somatostatin analogue 111 In-octreotide), hormone transporters (radiolabelled MIBG) or molecular targets (radiolabelled anti-CEA monoclonal antibodies) by MTC lesions are available; these tracers may be used also for the palliative treatment of advanced MTC. Interesting perspectives for MTC imaging are offered by PET radiopharmaceuticals.

The aim of the present study was to investigate the efficacy of infliximab for the treatment of extrapulmonary sarcoidosis. A prospective, randomised, double-blind, placebo-controlled trial was conducted, with infliximab at 3 and 5 mg x kg(-1) body weight administered over 24 weeks. Extrapulmonary organ severity was determined by a novel severity tool (extrapulmonary physician organ severity tool; ePOST) with an adjustment for the number of organs involved (ePOSTadj). In total, 138 patients enrolled in the trial of infliximab versus placebo for the treatment of chronic corticosteroid-dependent pulmonary sarcoidosis. The baseline severity of extrapulmonary organ involvement, as measured by ePOST, was similar across treatment groups. After 24 weeks of drug-therapy study, the change from baseline to week 24 in ePOST was greater for the combined infliximab group compared with the placebo group. After adjustment for the number of extrapulmonary organs involved, the improvement in ePOSTadj observed in the combined infliximab group was also greater than that observed in placebo-treated patients, after 24 weeks of therapy. The improvements in ePOST and ePOSTadj were not maintained during a subsequent 24-week washout period. Infliximab may be beneficial compared with placebo in the treatment of extrapulmonary sarcoidosis in patients already receiving corticosteroids, as assessed by the severity tool described in the present study.

ACCESS (A Case Control Etiologic Study of Sarcoidosis) was funded by the National Institutes of Health and collected data on 704 newly diagnosed, biopsy-proven cases of sarcoidosis and control subjects matched by age, sex, race, and geographic area. The goal of this study was to generate hypotheses about the etiology of sarcoidosis. The major hypothesis of the ACCESS investigators was that sarcoidosis occurs in genetically susceptible individuals through alteration in immune response after exposure to an environmental, occupational, or infectious agent. Strict criteria were used for the diagnosis of sarcoidosis and definitions of specific organ involvement were developed. The patients recruited for ACCESS represent the best clinical description of sarcoidosis at presentation in the United States. The study investigated the following: occupational/environmental triggers using a detailed questionnaire, infectious agents in the blood by polymerase chain reaction of 16s rDNA of microorganisms and cultures for cell wall-deficient mycobacteria, and genetic associations using a questionnaire to determine familial aggregation and candidate gene analysis. No single cause of sarcoidosis was identified. The results of this study are reviewed and possible lessons learned are discussed.

Papillary thyroid carcinoma (PTC) is universally regarded as a curable malignancy with a favorable prognosis. However, a minority of patients may present, or subsequently develop, locoregional and distant metastases that may adversely affect survival. The value of the various staging methods is complicated by different approaches to diagnostic, therapeutic and follow-up strategies. We aimed at assessing the prognostic factors and survival rate in a large cohort of patients treated and followed up in the same center.A total of 1858 patients with PTC operated on by the same surgeon, and followed in the same center over a period of 35 years, were included. Total thyroidectomy was performed in the majority of patients after I-131 diagnostic scans and thyroglobulin assays. When the latter 2 were positive, therapy with I-131 was given. Follow-up was performed periodically and further therapy doses were administered when necessary. All patients were maintained on life-long thyroxine.Ninety-three patients (5%) developed evidence of locoregional or distant metastases after an average follow-up period of 7.9 years (range 1.53-30.5 years). Univariate analysis showed all variables (except for gender) to be significantly correlated with disease recurrence and survival. Multivariate analysis showed 4 variables to be significant and independent prognostic factors: patient age at first treatment, extent of disease, extent of surgery, and the presence of I-131 positive metastases.Our data agree with other scoring systems in that patient age at first treatment and the extent of disease are significant and independent prognostic factors. However, and at variance with other methods, we found that the extent of primary surgery and the presence of I-131 positive or negative metastases have similar prognostic significance. In high risk patients, total thyroidectomy and lymphadenectomy followed by I-131 treatment and TSH-suppressive hormonal therapy are recommended.

Objective Neiva (a southern Colombia city) is endemic for dengue fever and dengue haemorrhagic fever. Neiva has suffered outbreaks of dengue, that in 2004 being the latest one. This study was designed to characterise epidemiological and clinical data from that outbreak of dengue. Material and Methods This was a descriptive, retrospective study of children aged less than 13 years who were admitted to the University Hospital and fulfilled the WHO's clinical and laboratory criteria for dengue or dengue haemorrhagic fever. Demographic, clinical and paraclinical data were recorded and analysed using Chi square (chi2) bivariate tabular test. Results 105 children were diagnosed as suffering from either dengue haemorrhagic fever (87.6%) or dengue fever (12.4%); 67% of them were aged less than 5 years. Girls were more frequently affected by severe clinical manifestations. 83% of the children were admitted during the first six days of the disease; dengue shock syndrome was diagnosed in 20% and 76% presented clinical complications (chi2 29.53, gl 6, p=0.0000). Aminotransferases were 3 to 5 times above normal levels. There was a statistical correlation between low platelet count (less than 20 000 per mm3) and shock during admission (chi2 20.65, gl 4, p=0.0004). Complications arose during clinical evolution in 32% of the cases (13% myocarditis, 19% hepatitis or encephalitis and 2% sepsis). Conclusion The clinical and epidemiological characteristics observed in this cohort evidenced differences in age, gender and organs affected compared to data described in the literature; there was a high incidence of myocarditis.

Primary hyperparathyroidism (PHPT) is an increasingly diagnosed disease worldwide. In most cases, PHPT is related to the presence of a solitary parathyroid adenoma (PA). Fifty percent or more of newly diagnosed PHPT patients are asymptomatic, and there is debate among endocrinologists and endocrine surgeons about whether or not such patients should be treated.Usually, in a PHPT patient with a solitary PA that is well localised pre-operatively, a parathyroidectomy with limited or minimally invasive neck exploration is offered. The diffusion of minimally invasive neck exploration procedures is a consequence of the significant improvement in the accuracy of pre-operative imaging (mainly scintigraphic) techniques; these techniques have changed the surgical strategy to PHPT, from the wide traditional bilateral neck exploration to limited neck exploration.The present review considers developments during the past 10-15 years with regard to both the accuracy of pre-operative localising imaging techniques and intra-operative minimally invasive procedures in order to provide endocrinologists and endocrine surgeons with further information about the newly available diagnostic and therapeutic tools for use in PHPT patients with a solitary PA.

Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation with tremendous clinical heterogeneity and uncertain pathobiology and lacking in clinically useful biomarkers. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study is an observational cohort study designed to explore the role of the lung microbiome and genome in these two diseases. This article describes the design and rationale for the GRADS study sarcoidosis protocol. The study addresses the hypothesis that distinct patterns in the lung microbiome are characteristic of sarcoidosis phenotypes and are reflected in changes in systemic inflammatory responses as measured by peripheral blood changes in gene transcription. The goal is to enroll 400 participants, with a minimum of 35 in each of 9 clinical phenotype subgroups prioritized by their clinical relevance to understanding of the pathobiology and clinical heterogeneity of sarcoidosis. Participants with a confirmed diagnosis of sarcoidosis undergo a baseline visit with self-administered questionnaires, chest computed tomography, pulmonary function tests, and blood and urine testing. A research or clinical bronchoscopy with a research bronchoalveolar lavage will be performed to obtain samples for genomic and microbiome analyses. Comparisons will be made by blood genomic analysis and with clinical phenotypic variables. A 6-month follow-up visit is planned to assess each participant’s clinical course. By the use of an integrative approach to the analysis of the microbiome and genome in selected clinical phenotypes, the GRADS study is powerfully positioned to inform and direct studies on the pathobiology of sarcoidosis, identify diagnostic or prognostic biomarkers, and provide novel molecular phenotypes that could lead to improved personalized approaches to therapy for sarcoidosis.

Unexpected radioiodine distributions may be encountered on post-therapy I-131 thyroid cancer scans due to a range of benign physiological processes, causing diagnostic dilemma and potentially mimicking metastatic disease. We present two cases of intense focal uptake related to concentration of radioiodine activity on wrist-watches by differing mechanisms, which should be confirmed by clinical history and not be mistaken for metastatic disease.

The aim of this study was to establish the clinical efficacy of the "low sestamibi dose" (LSD) protocol to perform thyroid and parathyroid radioguided surgery in a large series of patients homogeneously studied and operated on by the same surgeon. The LSD protocol was initially developed in our center to cure primary hyperparathyroid (PHPT) patients with a high likelihood of a solitary parathyroid adenoma (PA) by minimally invasive radioguided surgery (MIRS). Since then, the same protocol has been applied to differentiated thyroid cancer (DTC) patients with 131I-negative, but sestamibi-positive, locoregional recurrent disease in order to obtain radical radioguided extirpation of tumoral lesions at reoperation.We reviewed the clinical charts of 453 consecutive patients referred at the surgical department at Padova University (Padova, Italy) to investigate a PHPT or a DTC recurrence: 336 patients (74.2%) met the inclusion criteria for radioguided surgery, and these patients were analyzed for the aim of this study. There were 298 patients affected by PHPT with a high likelihood of a solitary sestamibipositive PA and 38 DTC patients affected by 131I-negative, but sestamibi-positive, locoregional recurrence. All patients underwent a preoperative imaging work-up, including sestamibi scintigraphy (doubletracer subtraction scan in PHPT patients and single-tracer, wash-out scan in DTC patients) and high-resolution neck ultrasonography (US). The LSD protocol we developed consists of the intravenous injection of a very low (1 mCi) sestamibi dose in the operating theater just 10 minutes before commencing intervention for the purpose of radioguided surgery only. At variance with the traditional "high (20-25 mCi) sestamibi dose (HSD)" protocol in which imaging and radioguided surgery are obtained in the same day, in the LSD protocol, imaging and radioguided surgery are performed in different days. The LSD protocol allows some advantages over the HSD protocol: (1) more time for acquiring and interpreting preoperative imaging (planar scintigraphy, single-photon emission computed tomography [SPECT], US); (2) an accurate selection of patients to whom MIRS is offered, especially in countries where the prevalence of nodular goiter with sestamibi-avid thyroid nodules (exclusion criteria for MIRS) is relatively high, as in mid-south-European countries; (3) it facilitates the work planning in the operating theater (bilateral neck exploration requires an operating time of at least double to that of MIRS); and (4) the radiation exposure dose to operating theater personnel is very low-substantially negligible, using the LSD protocol: This aspect assumes great importance in countries where radioproteximetric rules are stringent, as in Europe.PHPT patients. MIRS was successfully performed by a 1.5-2-cm skin incision in 287 of 298 PHPT patients (96.3%) in whom such an approach was scheduled on the basis of preoperative imaging, including 41 of 57 patients (71.9%) who had previously received thyroid or unsuccessful parathyroid surgery in another center. No case of major intraoperative complication was recorded. No case of persistent or recurrent PHPT was observed during postsurgical follow-up. DTC patients. A total of 79 metastatic lesions were intraoperatively detected by the gamma probe and successfully removed (68 of them had been correctly visualized at preoperative sestamibi scintigraphy). During subsequent follow-up, 18 patients (72%) were considered disease-free, whereas 7 had persistent disease (increased serum thyroglobulin levels). The radiation exposure dose to the surgeon using the LSD protocol was 1.2 uSi/hour, that is, 20-30-fold lower than that delivered with the HSD protocol used for PHPT patients and with the 131I protocol used for DTC patients with recurrence.On the basis of our data, it can be concluded that the LSD protocol is a safe and effective protocol to perform in both MIRS in PHPT patients and radioguided reoperation in DTC patients with 131I-negative recurrence. Furthermore, from a radioproteximetric point of view, in comparison with other radioguided protocols used for the same purposes, the LSD protocol minimizes the radiation-exposure dose to the surgeon and operating theater personnel.

Background: Some sarcoidosis patients never need therapy, but many still require therapy more than 2 years after initial diagnosis. Aim: To determine what features at initial presentation are associated with treatment 2 years later. Methods: Patients with biopsy-confirmed sarcoidosis enrolled in the ACCESS (A Case Control Etiologic Study of Sarcoidosis) study were initially evaluated within 6 months of diagnosis. Pulmonary function, chest X-ray and dyspnoea score were measured, and systemic therapy for the sarcoidosis recorded. Organ involvement was assessed using a standardized instrument. A subset ( n = 215) were seen 18–24 months later for follow-up, and these patients constitute our study group. Results: Ten patients had only received therapy before the first visit, with no further therapy, and were excluded from analysis. Of the remaining 205, 95 were not on therapy at the initial visit and 75 (79%) of these were never treated during follow-up. Of the 110 initially on therapy, 52 (47%) remained on therapy at follow-up. Other initial features associated with continued therapy were the level of dyspnoea and predicted vital capacity. On logistic regression, only dyspnoea and therapy at initial visit remained significant. Patients on systemic therapy at initial evaluation were more likely to be on therapy at follow-up (OR 3.6, p = 0.003). Neither ethnicity nor gender independently predicted therapy at follow-up. Discussion : This study group represents a sample of newly diagnosed sarcoidosis patients. However, this is a referral population, and there was no set protocol for treatment. Use of systemic therapy within the first 6 months after diagnosis appears to be strongly associated with continued use of therapy 2 years later.

Purpose: Met, an oncogene product and receptor tyrosine kinase, is a keystone molecule for malignant progression in solid human tumors. We are developing Met-directed imaging and therapeutic agents, including anti-Met monoclonal antibodies (MetSeekTM). In this study, we compared two antibodies, Met5 and Met3, for nuclear imaging of human and canine Met-expressing tumor xenografts in nude mice. Experimental Design: Xenografts representing cancers of three different human tissue origins and metastatic canine prostate cancer were raised s.c. in host athymic nude mice. Animals were injected i.v. with I-125-Met5 or I-125-Met3, posterior total body gamma camera images were acquired for several days postinjection, and quantitative region-of-interest activity analysis was done. Results: PC-3, SK-LMS-1/HGF, and CNE-2 xenografts imaged with I-125-Met5 were compared with PC-3, SK-LMS-1/HGF, and DU145 xenografts imaged with I-125-Met3. Nuclear imaging contrast was qualitatively similar for I-125-Met5 and I-125-Met3 in PC-3 and SK-LMS-1/HGF host mice. However, by region-of-interest analysis, the set of human tumors imaged with I-125-Met3 exhibited a pattern of rapid initial tumor uptake followed by a continuous decline in activity, whereas the set of human tumors imaged with I-125-Met5 showed slow initial uptake, peak tumor-associated activity at 1 day postinjection, and persistence of activity in xenografts for at least 5 days. GN4 canine prostate cancer xenografts were readily imaged with I-125-Met5. Conclusions: We conclude that radioiodinated Met3 and Met5 offer qualitatively similar nuclear images in xenograft-bearing mice, but quantitative considerations indicate that Met5 might be more useful for radioimmunotherapy. Moreover, canine prostate cancer seems to be a suitable model for second-stage preclinical evaluation of Met5.

We conducted a medical screening for beryllium disease of 577 former workers from a beryllium processing facility. The screening included a medical and work history questionnaire, a chest radiograph, and blood lymphocyte proliferation testing for beryllium. A task exposure and a job exposure matrix were constructed to examine the association between exposure to beryllium and the development of beryllium disease. More than 90% of the cohort completed the questionnaire, and 74% completed the blood and radiograph component of the screening. Forty-four (7.6%) individuals had definite or probable chronic beryllium disease (CBD), and another 40 (7.0%) were sensitized to beryllium. The prevalence of CBD and sensitization in our cohort was greater than the prevalence reported in studies of other beryllium-exposed cohorts. Various exposure measures evaluated included duration; first decade worked; last decade worked; cumulative, mean, and highest job; and highest task exposure to beryllium (to both soluble and nonsoluble forms). Soluble cumulative and mean exposure levels were lower in individuals with CBD. Sensitized individuals had shorter duration of exposure, began work later, last worked longer ago, and had lower cumulative and peak exposures and lower nonsoluble cumulative and mean exposures. A possible explanation for the exposure-response findings of our study may be an interaction between genetic predisposition and a decreased permanence of soluble beryllium in the body. Both CBD and sensitization occurred in former workers whose mean daily working lifetime average exposures were lower than the current allowable Occupational Safety and Health Administration workplace air level of 2 microg/m3 and the Department of Energy guideline of 0.2 microg/m3.

In this paper we review the controversies in diagnostic approaches to follicular thyroid nodules with indeterminate cytology. The authors consider some of the controversies surrounding the indeterminate follicular thyroid nodule, including the definition and the postoperative outcome. Among the techniques that may improve preoperative diagnostic accuracy are large needle aspiration biopsy and immunohistochemistry for galectin-3.

Study objectives Sarcoidosis is a granulomatous disorder with heterogeneous clinical manifestations, which are potentially reflective of a syndrome with different etiologies leading to similar histologic findings. We examined the relationship between environmental and occupational exposures, and the clinical phenotype of sarcoidosis. Design We performed a cross-sectional study of incident sarcoidosis cases that had been identified by A Case Control Etiologic Study of Sarcoidosis. Subjects were categorized into the following two groups: (1) pulmonary-only disease; and (2) systemic disease (with or without pulmonary involvement). Logistic regression was used to examine the associations of candidate exposures with clinical phenotype. Setting Ten academic medical centers across the United States. Patients The current study included 718 subjects in whom sarcoidosis had been diagnosed within 6 months of study enrollment. Patients met the following criteria prior to enrollment: (1) tissue confirmation of noncaseating granulomas on tissue biopsy on one or more organs within 6 months of study enrollment with negative stains for acid-fast bacilli and fungus; (2) clinical signs or symptoms that were consistent with sarcoidosis; (3) no other obvious explanation for the granulomatous disease; and (4) age > 18 years. Measurements and results Several exposures were associated with significantly less likelihood of having extrapulmonary disease in multivariate analysis, including agricultural organic dusts and wood burning. The effects of many of these exposures were significantly different in patients of different self-defined race. Conclusions The differentiation of sarcoidosis subjects on the basis of clinical phenotypes suggests that these subgroups may have unique environmental exposure associations. Self-defined race may play a role in the determination of the effect of certain exposures on disease phenotypes.

Sarcoidosis, a systemic granulomatous disease of unknown etiology, likely results from an environmental insult in a genetically susceptible host. In the US, African Americans are more commonly affected with sarcoidosis and suffer greater morbidity than Caucasians. We searched for sarcoidosis susceptibility loci by conducting a genome-wide, sib pair multipoint linkage analysis in 229 African-American families ascertained through two or more sibs with a history of sarcoidosis. Using the Haseman-Elston regression technique, linkage peaks with P-values less than 0.05 were identified on chromosomes 1p22, 2p25, 5p15-13, 5q11, 5q35, 9q34, 11p15 and 20q13 with the most prominent peak at D5S2500 on chromosome 5q11 (P=0.0005). We found agreement for linkage with the previously reported genome scan of a German population at chromosomes 1p and 9q. Based on the multiple suggestive regions for linkage found in our study population, it is likely that more than one gene influences sarcoidosis susceptibility in African Americans. Fine mapping of the linked regions, particularly on chromosome 5q, should help to refine linkage signals and guide further sarcoidosis candidate gene investigation.

Past research suggests that environmental factors may be associated with sarcoidosis risk. We conducted a case control study to test a priori hypotheses that environmental and occupational exposures are associated with sarcoidosis. Ten centers recruited 706 newly diagnosed patients with sarcoidosis and an equal number of age-, race-, and sex-matched control subjects. Interviewers administered questionnaires containing questions regarding occupational and nonoccupational exposures that we assessed in univariable and multivariable analyses. We observed positive associations between sarcoidosis and specific occupations (e.g., agricultural employment, odds ratio [OR] 1.46, confidence interval [CI] 1.13-1.89), exposures (e.g., insecticides at work, OR 1.52, CI 1.14-2.04, and work environments with mold/mildew exposures [environments with possible exposures to microbial bioaerosols], OR 1.61, CI 1.13-2.31). A history of ever smoking cigarettes was less frequent among cases than control subjects (OR 0.62, CI 0.50-0.77). In multivariable modeling, we observed elevated ORs for work in areas with musty odors (OR 1.62, CI 1.24-2.11) and with occupational exposure to insecticides (OR 1.61, CI 1.13-2.28), and a decreased OR related to ever smoking cigarettes (OR 0.65, CI 0.51-0.82). The study did not identify a single, predominant cause of sarcoidosis. We identified several exposures associated with sarcoidosis risk, including insecticides, agricultural employment, and microbial bioaerosols.

Importance Our previous studies demonstrated that tumors significantly decrease in size and metabolic activity after delivery of 45 Gy of fractionated radiatiotherapy (RT), and that metabolic shrinkage is greater than anatomic shrinkage. This study aimed to determine whether 18 F-fludeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) acquired during the course of treatment provides an opportunity to deliver higher-dose radiation to the more aggressive areas of the tumor to improve local tumor control without increasing RT-induced lung toxicity (RILT), and possibly improve survival. Objective To determine whether adaptive RT can target high-dose radiation to the FDG-avid tumor on midtreatment FDG-PET to improve local tumor control of locally advanced non–small-cell lung cancer (NSCLC). Design, Setting, and Participants A phase 2 clinical trial conducted at 2 academic medical centers with 42 patients who had inoperable or unresectable stage II to stage III NSCLC enrolled from November 2008, to May 2012. Patients with poor performance, more than 10% weight loss, poor lung function, and/or oxygen dependence were included, providing that the patients could tolerate the procedures of PET scanning and RT. Intervention Conformal RT was individualized to a fixed risk of RILT (grade >2) and adaptively escalated to the residual tumor defined on midtreatment FDG-PET up to a total dose of 86 Gy in 30 daily fractions. Medically fit patients received concurrent weekly carboplatin plus paclitaxel followed by 3 cycles of consolidation. Main Outcomes and Measures The primary end point was local tumor control. The trial was designed to achieve a 20% improvement in 2-year control from 34% of our prior clinical trial experience with 63 to 69 Gy in a similar patient population. Results The trial reached its accrual goal of 42 patients: median age, 63 years (range, 45-83 years); male, 28 (67%); smoker or former smoker, 39 (93%); stage III, 38 (90%). Median tumor dose delivered was 83 Gy (range, 63-86 Gy) in 30 daily fractions. Median follow-up for surviving patients was 47 months. The 2-year rates of infield and overall local regional tumor controls (ie, including isolated nodal failure) were 82% (95% CI, 62%-92%) and 62% (95% CI, 43%-77%), respectively. Median overall survival was 25 months (95% CI, 12-32 months). The 2-year and 5-year overall survival rates were 52% (95% CI, 36%-66%) and 30% (95% CI, 16%-45%), respectively. Conclusions and Relevance Adapting RT-escalated radiation dose to the FDG-avid tumor detected by midtreatment PET provided a favorable local-regional tumor control. The RTOG 1106 trial is an ongoing clinical trial to validate this finding in a randomized fashion. Trial Registration clinicaltrials.gov Identifier:NCT01190527

PET/CT with (18)F-fluorodeoxyglucose (FDG) or using different radiocompounds has proven accuracy for detection of adrenal metastases in patients undergoing cancer staging. It can assist the diagnostic work-up in oncology patients by identifying distant metastases to the adrenal(s) and defining oligometastatic disease that may benefit from targeted intervention. In patients with incidentally discovered adrenal nodules, so-called adrenal "incidentaloma" FDG PET/CT is emerging as a useful test to distinguish benign from malignant etiology. Current published evidence suggests a role for FDG PET/CT in assessing the malignant potential of an adrenal lesion that has been 'indeterminately' categorized with unenhanced CT, adrenal protocol contrast-enhanced CT, or chemical-shift MRI. FDG PET/CT could be used to stratify patients with higher risk of malignancy for surgical intervention, while recommending surveillance for adrenal masses with low malignant potential. There are caveats for interpretation of the metabolic activity of an adrenal nodule on PET/CT that may lead to false-positive and false-negative interpretation. Adrenal lesions represent a wide spectrum of etiologies, and the typical appearances on PET/CT are still being described, therefore our goal was to summarize the current diagnostic strategies for evaluation of adrenal lesions and present metabolic and anatomic appearances of common and uncommon adrenal lesions. In spite of the emerging role of PET/CT to differentiate benign from malignant adrenal mass, especially in difficult cases, it should be emphasized that PET/CT is not needed for most patients and that many diagnostic problems can be resolved by CT and/or MR imaging.

This is an interactive module aimed at senior medical students and radiology residents during a nuclear medicine rotation that discusses the common imaging findings of conditions that cause hyperthyroidism. Typical cases of Graves disease, Plummer disease, toxic multinodular goiter, and thyroiditis are presented in an interactive fashion using illustrative case examples accompanied by multiple-choice questions. Issues that arise following radioiodine therapy with regard to Nuclear Regulatory Commission rules, and causes and mechanisms of iodine-induced hyperthyroidism and hypothyroidism are also discussed. It is anticipated that an individual will go through the presentation in a self-guided manner. It will likely take approximately 1 hour to complete the entire presentation. While this basic presentation should suffice for medical students and junior residents, it is not meant to be a definitive source of facts for more senior radiologists. Those that require more in-depth information can utilize some of the selected resources listed at the end of the presentation or consult a nuclear medicine textbook. Because of the question and answer format, it is hoped that this presentation will be useful for medical students, radiology residents, and even practicing radiologists as a review tool.

Endocrine tumors are hormonally active benign or malignant neoplasms arising within endocrine organs or from specialized cells of the amine precursor uptake and decarboxylation (APUD) system that are increasing in incidence as a result of sensitive biochemical tests and high-resolution diagnostic imaging. Not unlike tumors of other systems, endocrine neoplasms are heterogenous with variable prognosis characterized by well-differentiated thyroid cancer with very favorable outcome, medullary thyroid cancer and neuroendocrine-type tumors with intermediate outcomes, and anaplastic thyroid, adrenocortical, and Merkel cell cancers with the poorest clinical outcomes. Medical imaging has become a key component in diagnosis and staging of endocrine malignancies; however, even with great advances in computed tomography and magnetic resonance imaging, detection of small primary tumors and metastases continues to be a challenge. Complimentary functional imaging targets tumor cellular processes that actively accumulate radiopharmaceuticals, allowing sensitive and highly specific oncological imaging. Surveillance of endocrine malignancies commonly combines functional imaging with tumor-specific laboratory biomarkers. Furthermore, functional imaging studies can predict efficacy of radionuclide or receptor-based therapies. The last decade has seen an increasing use of combined PET-CT and SPECT-CT scanners designed to create functional and anatomic maps with resultant incremental diagnostic capabilities. These technologies together with the development of novel PET and SPECT radiopharmaceuticals make patient-individualized functional imaging protocols possible, based on the histological grade, degree of differentiation, and genetic profile of their endocrine neoplasm.