Positive Uptake Research Articles

MON-386 Finding Truth from Two False-Positives

Certain medications can interfere with catecholamines levels and result in a misleading diagnosis of pheochromocytoma. Tricyclic antidepressants, alpha-blockers, beta-blockers, and acetaminophens are the most common cause of falsely elevated levels of catecholamines. To confirm and localize pheochromocytoma, 123I-Metaiodobenzylguanidine (123I-MIBG) scintigraphy scan is usually performed following a biochemical test if CT or MRI has failed to detect the tumor. Here we describe a 48-year-old African-American male who was found to have a medication-related elevation in catecholamines with positive 123I-MIBG adrenal uptake. He was referred to the endocrinology clinic for elevated plasma epinephrine, norepinephrine, and dopamine levels. His primary care physician obtained catecholamines levels for recurrent episodes of anxiety, sweating, and dizziness. No history of hypertension was noted. His medications include alprazolam for anxiety, hydrocodone/acetaminophen for chronic back pain, valproic acid for mood-stablilizing, and escitalopram for depression. At the first visit, his blood pressure was 162/110. Otherwise, an unremarkable physical exam was noted. Initial blood work at an outside facility showed plasma dopamine > 3000 pg/mL (Ref 0-20 pg/mL), epinephrine 6827 pg/mL (Ref 0-62 pg/mL), and norepinephrine 51919 pg/mL (Ref 80-520 pg/mL). The patient underwent MRI of the abdomen and pelvis before the referral, which was unremarkable, and had an 123I-MIBG scan that showed increased accumulation over the left adrenal gland; none was seen over the right adrenal gland. We withheld his medications except for alprazolam. Catecholamine levels were retested after four weeks and showed normal plasma epinephrine, norepinephrine, metanephrine, and normetanephrine levels. The 123I-MIBG scan is highly sensitive and specific for the detection of pheochromocytoma. However, 123I-MIBG uptake can also be seen in normal adrenal medulla (16% of scans after 48 h). The pattern of 123I-MIBG uptake may be asymmetrical between the left and right adrenals, and therefore, caution should be applied in interpreting the images obtained, particularly to avoid unnecessary or misguided surgery. This case demonstrates a unilateral 123I-MIBG adrenal uptake possibly associated with medications. It is expected that the uptake would be bilateral, given the systemic effect of the medications. Nonetheless, in this case, unilateral adrenal uptake was found. Medication-induced catecholamine elevation has to be ruled out before further investigation for pheochromocytoma. This step is crucial given the non-specific symptoms of pheochromocytoma and the possibility of having false catecholamines elevation and false 123I-MIBG uptake, both of which further challenge the diagnosis of pheochromocytoma.

SAT-320 A Synonymous Pathogenic Variant (p.l180=) in SDHB Gene Identified in a Young Patient with Abdominal Paraganglioma

Background: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from chromaffin cells. More than 30% of patients with PPGL have a hereditary predisposition. To date, at least 14 tumor susceptibility genes have been described. Mutations in the succinate dehydrogenase complex iron sulfur subunit B gene (SDHB) are more associated with paragangliomas and metastatic disease. Patients who are young, with larger tumors (>6 cm), positive genetic testing (especially SDHB) or paraganglioma have a higher risk of metastasis development. Case Report: A 14-yr-old boy was referred to investigate severe hypertension and paroxysmal headache, pallor and tachycardia. Biochemical testing for catecholamine-secreting PPGLs showed: 24h urine metanephrines 1.9 µg (normal range, 0.05 to 1.2), plasma normetanephrine 13.3 nmol/L (<0.9 nmol/L), plasma metanephrine <0.2 nmol/L (<0.5 nmol/L), 24h urine norepinephrine 987 µg (14 to 80), 24h urine epinephrine 0 (0.5 to 20 µg) and 24h urine dopamine 391 µg (65 to 400). Magnetic resonance imaging (MRI) revealed a 6.5 cm heterogenous and high-vascular mass in right adrenal gland topography. A strong positive uptake was evidenced in the metaiodobenzylguanidine (MIBG) scintigraphy. A selective α1-receptor blocker (prazosin) was started to control blood pressure and adrenergic symptoms. The patient underwent laparoscopic surgery and anatomopathological analysis revealed a 5.5 cm paraganglioma (PASS criteria= 3). The normal right adrenal gland was identified in the histopathology and there was no continuity between normal adrenal gland and neoplasia. After one year of follow-up, the patient is in complete remission. Genetic analysis by Sanger automated sequencing revealed no pathogenic variants in VHL and SDHD genes. We identified a heterozygous germline synonymous variant c.540 G>A (p.L180=), involving a G>A transition in the last nucleotide of SDHB exon 5. This synonymous variant results in alternative splicing of the SDHB primary transcript. This germline variant was previously reported in a 12-yr-old patient with isolated jugulotympanic paraganglioma, but it has not been associated with catecolamine-secreting paraganglioma. Neck MRI revealed no abnormalities in our patient. Conclusion: We report here a synonymous pathogenic variant in SDHB exon 5 associated with an abdominal functioning paraganglioma. Annual screening for multifocal disease (abdominal and neck PPGLs) and malignancy should be performed.

SAT-LB059 NET or NOT: Physiological Uptake in Pancreatic Head on Somatostatin Receptor Based Imaging

Introduction Neuroendocrine tumors (NETs) are neoplasms that can arise from the neuroendocrine cells distributed widely throughout the body. Majority of NETs overexpress somatostatin receptors (SSTR) on their cell surface. This biologic characteristic is exploited in the SSTR-based imaging such as 111In octreotide scintigraphy and 68Ga DOTATATE positron emission tomography (PET)/CT. These modalities are currently considered standard for initial evaluation of suspected NETs. Although highly sensitive and specific, recent reports demonstrate a concerning incidence of “false-positive” physiologic uptake of these tracers in the pancreatic head - a confounding common site of NET involvement. Case report: A 78 year-old woman presented to clinic with a year-long history of diarrhea. Serum vasoactive intestinal peptide (VIP) levels were slightly elevated at 134.2 pg/mL. CT showed a mildly enhancing 2.5x1.8x2.8 cm area in the pancreatic uncinate process which corresponded to moderate focal uptake with 68Ga DOTATATE PET/CT. A presumptive diagnosis of NET was made, and the patient was scheduled to undergo Whipple’s surgery. She sought a second opinion at our institution. A subsequent MRI showed no lesion in the uncinate process and the patient’s surgery was deferred. Thereafter, her VIP levels spontaneously normalized. Endoscopic ultrasound (EUS) with fine needle aspiration cytology of the uncinate process showed normal pancreatic acini with no evidence of NET. Conclusion Conspicuous physiological uptake has been reported in the pancreatic head on 16-70% of 68Ga DOTATATE or 68Ga DOTANOC PET/CT scans, and 26% of the 111In octreotide scintigraphy scans.1 Image-based quantitative attempts to distinguish physiologic from pathologic uptake using SUVmax have rendered mixed results. When evaluating SSTR-based imaging uptake in the pancreatic head, patients can benefit from a higher index of suspicion of false positive uptake. Such cases require additional confirmation by means such as MRI or EUS. The patient described above also had mild contrast enhancement on CT, but an MRI didn’t show any corresponding lesion. Because of potential morbidity and mortality related to false positive uptake, a systematic review with evidence-based recommendations for imaging may benefit patient care. 1. Brabander T, et al. Physiological Uptake in the Pancreatic Head on Somatostatin Receptor Scintigraphy Using [111In-DTPA]Octreotide: Incidence and Mechanism. Clin Nucl Med 2017;42:15-9. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Overall survival and progression-free survival in patients with primary brain tumors after treatment: is the outcome of [18F] FDOPA PET a prognostic factor in these patients?

To investigate the progression-free survival (PFS) and the overall survival (OS) in a population affected by primary brain tumors (PBT) evaluated by [18F]-L-dihydroxyphenylalanine ([18F] FDOPA) positron emission tomography/computed tomography (PET/CT). 133 subjects with PBT (65 women and 68 men, mean age 45 ± 10years old) underwent 18F FDOPA PET/CT after treatment. Of them, 68 (51.2%) were Grade II, 34 (25.5%) were Grade III and 31 (23.3%) were Grade IV. PET/CT was scored as positive or negative and standardized uptake value ratio (SUVr) was calculated as the ratio between SUVmax of the lesion vs. that of the background. Patients have been observed for a mean of 24months. The outcome of [18F] FDOPA PET/CT scan was significantly related to the OS and PFS in Grade II gliomas. In Grade II PBT, the OS proportions at 24months were 100% in subjects with a negative PET/CT scan and 82% in those with a positive scan. Gehan-Breslow-Wilcoxon test showed a significant difference in the OS curves (P = 0.03) and the hazard-ratio was equal to 5.1 (95% CI of ratio 1.1-23.88). As for PFS, the proportion at 24months was 90% in subjects with a negative PET/CT scan and 58% in those with a positive scan. Gehan-Breslow-Wilcoxon test showed a significant difference in the OS curves (P = 0.007) and the hazard-ratio was equal to 4.1 (95% CI of ratio 1.3-8). We did not find any significant relationship between PET outcome and OS and PFS in Grade III and IV PBT. A positive [18F] FDOPA PET/CT scan is related to a poor OS and PFS in subjects with low-grade PBT. This imaging modality could be considered as a prognostic factor in these subjects.

Abstract #587 Grave’s Disease? False Positive Radioactive Iodine Uptake Scan in the Presence of Biotin Induced Increase in TSH Antibody and Low TSH

Abstract #587 Grave’s Disease? False Positive Radioactive Iodine Uptake Scan in the Presence of Biotin Induced Increase in TSH Antibody and Low TSH

Diagnostic accuracy and safety of 16α-[18F]fluoro-17β-oestradiol PET-CT for the assessment of oestrogen receptor status in recurrent or metastatic lesions in patients with breast cancer: a prospective cohort study

A biopsy of first recurrence or metastatic disease is recommended to re-evaluate oestrogen receptor status in patients with breast cancer and to select appropriate treatment. However, retesting for oestrogen receptor status with rebiopsy is not always feasible, depending on lesion location and the risk associated with biopsy, and in these cases clinicians continue to treat patients according to the oestrogen receptor status of the primary tumour. Consequently suboptimal therapy might be offered to these patients. We assessed the diagnostic accuracy and safety of 16α-[18F]fluoro-17β-oestradiol (18F-FES) PET-CT to assess oestrogen receptor status in patients with recurrent or metastatic breast cancer. We did a prospective cohort study at the Asan Medical Center, Seoul, South Korea. Eligible patients had breast cancer, with first recurrence or metastatic disease at presentation, were 19 years or older, and had an Eastern Cooperative Oncology Group performance status of 0-2. The primary objective was to show the agreement between qualitative 18F-FES PET-CT interpretation and the results of oestrogen receptor expression by immunohistochemical assay, a non-reference standard test. Whole-body 18F-FES PET-CT imaging was done after intravenous injection of 111-222 MBq of 18F-FES, with dosing primarily determined by radiation dosimetry analysis. 18F-FES uptake above background intensity was interpreted as positive. Efficacy was assessed in all patients with histologically confirmed recurrent or metastatic breast cancer who received 18F-FES and had PET-CT images available (intention-to-diagnose analysis), and safety was assessed in all patients who received 18F-FES. This study is registered with ClinicalTrials.gov, number NCT01986569. Between Nov 27, 2013, and Nov 10, 2016, 93 patients were enrolled. Of the 85 patients included in the efficacy analysis, 47 (55%) were oestrogen receptor-positive and 38 (45%) were oestrogen receptor-negative. Positive status percent agreement between the 18F-FES PET-CT results and oestrogen receptor status by immunohistochemical assay was 76·6% (95% CI 62·0-87·7) and the negative status percent agreement was 100·0% (90·8-100·0). Patients who were oestrogen receptor-positive and had a positive 18F-FES PET-CT result had a significantly higher progesterone receptor expression than those who were oestrogen receptor-positive and had a negative 18F-FES PET-CT result (23 [68%] of 34 patients vs 0 of 11 patients; p<0·0001). The most common adverse event was procedural pain in nine (10%) of 90 patients injected with 18F-FES. No adverse events were related to the study drug except injection site pain in one (1%) patient. No serious adverse events were recorded. The high negative percent agreement between 18F-FES PET-CT and oestrogen receptor status by immunohistochemical assay in this cohort suggests that positive 18F-FES uptake by recurrent or metastatic oestrogen receptor-positive breast cancer lesions could be an alternative to oestrogen receptor assays in this setting. Staging assessment should include 18F-FES PET-CT when retesting oestrogen receptor status is not feasible. Asan Institute for Life Sciences, Ministry of Health and Welfare, South Korea.

Usefulness of respiratory-gated 18F-FDG PET/CT scan protocol in patients having positive myocardial 18F-FDG uptake.

The aim of this study were to estimate the influence of respiratory movement on the fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) imaging of patients having positive myocardial F-FDG uptake and to demonstrate an adequate respiratory-gated F-FDG PET/CT scan protocol. An anthropomorphic chest phantom containing a cardiac ventricle phantom was filled with an fluorine-18 solution and scanned in both a nonmoving state and a moving state with respiratory gating. In the nonmoving state, PET images were acquired in static mode (static PET), whereas in the moving state, PET images were acquired in a nongated mode (nongated PET), and in a gated mode (gated PET). The gated PET images were divided into 2-10 phases. The standardized uptake value (SUV)nongated ratio and SUVgated ratio (SUVnongated ratio or SUVgated ratio=SUVmean of nongated PET or gated PET/SUVmean of static PET) were calculated. In addition, nongated PET images and gated PET images were created from 12 sets of respiratory-gated clinical F-FDG PET/CT acquisitions. The clinical 12 gated PET data were divided into 2-8 phases. We measured SUVmax of cardiac volume data at each number of phases. In dividing into more than three phases, the SUVgated ratio remarkably improved. In dividing into more than five phases, rate of SUVmax improvement from nongated PET showed 5% in the analysis of clinical data. For a F-FDG PET/CT scan for patients with having positive myocardial F-FDG uptake, a respiratory-gated PET protocol divided into five phases is recommended, to minimize the influence of internal motion on cardiac accumulation.

Relationship between parathyroid gland scintigraphy and its histopathology, oxyphil cell content and volume: a retrospective study.

Mechanisms that are responsible for positive 99mTc-MIBI uptake in parathyroid glands are not clearly understood, some authors suggest there is a correlation between 99mTc MIBI accumulation and oxyphil cell content or parathyroid gland volume. The aim of our work was to assess the relationship between the pathological structure of parathyroids, their volume, oxyphil cell content and parathyroid 99mTc-MIBI retention. A total of 62 hyperfunctioning parathyroid glands in 46 patients were retrospectively analyzed. Preoperative 99mTc-MIBI scintigraphy was performed according to the double-phase and subtraction protocol. After surgery all glands were evaluated histologically, oxyphil cell content was assessed and volume of each excised gland was calculated. Scintigraphy was positive in 41 of 62 parathyroid glands (66%). The median volume of positive glands was larger than that of negative glands (1.33 ml vs 0.7 ml, p = 0.015). Of the parathyroid lesions, there were 14 (22.6%) cases of nodular hyperplasia, 23 (37.1%) cases of diffuse hyperplasia, and 25 (40.3%) cases of adenomas. A high (≥ 25%) oxyphil cell content was found in 16 glands (25.8%) and a low ( < 25%) oxyphil cell content in 46 (74.2%) glands. Histopathology of parathyroid glands was related to the scintigraphy result (p = 0.002), but not to the 99mTc-MIBI uptake pattern (p = 0.868). The overall result of scintigraphy was not related to the oxyphil cell content (p = 0.797). 99mTc-MIBI uptake pattern wasn't related to the oxyphil cell content (p = 0.833). In general, parathyroid lesions with low oxyphil cell content were larger than parathyroid glands with high oxyphil cell content (1.33 ml vs 0.5 ml, respectively; p = 0.01). The median volume of parathyroids containing a high number of oxyphil cells and having a prolonged 99mTc-MIBI retention was larger than those without prolonged 99mTc-MIBI retention (1.62 ml vs 0.3 ml, respectively; p = 0.008). The median volume of parathyroids with low oxyphil cells content and showing prolonged 99mTc-MIBI retention was larger than those without prolonged 99mTc-MIBI retention (1.95 ml vs 1.07 ml, respectively; p = 0.014). Our findings suggest that a positive scintigraphy result depends on parathyroid histopathology and gland volume and does not depend on the presence of oxyphil cells. Prolonged 99mTc-retention is not related to the parathyroid gland histopathology and the presence of oxyphil cells but to the gland volume.

The prognostic role of end of treatment FDG-PET-CT in patients with diffuse large B cell lymphoma can be improved by considering it with absolute monocyte count at diagnosis

It is well established that some patients with diffuse large B-cell lymphoma (DLBCL) and the negative end of treatment PET-CT (EOT-PET-CT) will relapse, while a proportion with positive uptake can still obtain long-term EFS. We reviewed data of 200 consecutive, previously untreated patients with DLBCL recorded in Italy and Israel between 2007 and 2015. We found that patients with negative EOT-PET-CT with AMC > 630/mmc have a 3-years EFS of 72%, compared to those with AMC ≤ 630/mmc that have an EFS of 84%. Furthermore, considering patients with positive EOT-PET-CT, those with AMC > 630/mmc have a 3-years EFS of 8%, while those with AMC ≤ 630/mmc have an EFS of 38%. Thus, it appears that combining the gold standard for response evaluation EOT-PET-CT with a simple and inexpensive parameter like AMC at diagnosis, further improves prognostication in DLBCL. Applying this simple method can be useful for all doctors working in lymphoma clinical practice.

Clinical Implications of Incidental Sinonasal Positive FDG Uptake on PET-CT.

Fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) has been increasingly used in the past decade. Incidental FDG-avid findings are encountered in these studies, several of which with clinical significance. However, the significance of incidental FDG-avid sinonasal findings has not been studied to date. Retrospective cohort study. A single tertiary medical center. The medical records were reviewed of patients with incidental sinonasal positive FDG uptake between 2007 and 2016 who referred for further otolaryngological diagnostic workup. A total of 26 patients were identified, all of whom underwent a diagnostic surgical procedure. Histopathology revealed chronic inflammation (n = 12, 46.1%), malignancy (n = 7, 26.9%), inverted papilloma (n = 4, 15.5%), and fungal infections (n = 3, 11.5%). A unilateral maxillary sinus with FDG uptake was documented for 16 (61.5%) patients. CT evidence of bilateral disease and mucosal or sinus wall thickening correlated with inflammatory disease. Incidental lesions with positive FDG uptake in the sinonasal cavities are at a high risk (40%) of being neoplastic. A diagnostic biopsy is advocated in these cases.

Diagnostic and Prognostic Value of CMR and Cardiac PET Imaging in Patients with Cardiac Sarcoidosis

Background: Cardiac Magnetic Resonance (CMR) and Positron Emission Tomography (PET) are employed to diagnose Cardiac Sarcoidosis (CS). However, their role in prognosis and guiding treatment is not well established. Objective: To discern the utility of CMR and PET in diagnosing and predicting adverse outcomes in CS. Methods: “Cardiac Sarcoidosis*” AND “Magnetic Resonance Imaging” OR “Positron Emission Tomography” were searched on PubMED, EMBASE and SCOPUS on 21st of September 2018 yielding 1180 articles. After exclusions, 26 studies were included in the meta-analysis. Results: 8 and 13 studies compared diagnostic value of CMR and PET, respectively against the diagnostic criteria of either the Japanese Ministry of Health or the Heart Rhythm Society. These showed a sensitivity of 75.7% [69.3–81.4] and 81.4% [76.7–85.4] for CMR and cardiac PET, respectively, to diagnose CS. The risk of ventricular arrhythmia was increased in patients with late gadolinium enhancement (LGE) on CMR (HR 3.32 [0.59–18.51], I2 = 58; N = 4) or positive FDG uptake on cardiac PET (HR 2.91 [1.68–5.06]; N = 3). The LVEF in the group with and without LGE on CMR was 54±9 and 57±7%, respectively. Absence of LGE on CMR predicted absence of ventricular arrhythmia (NPV = 96.7% [88.2%–99.1%]). LGE on CMR was also associated with increased risk of major adverse cardiac events (MACE) (HR: 8.20 [2.28–29.45], I2 = 81; N = 5). Conclusion: LGE on CMR and positive FDG uptake on cardiac PET are associated with high risk of ventricular arrhythmia. LGE on CMR imaging predicts high risk for MACE.

FDG-PET/CT for diagnosis and follow-up of necrotizing (malignant) external otitis.

Imaging is important for the diagnosis and follow-up of necrotizing external otitis (NEO). The best imaging modality is controversy. To suggest 2-deoxy-2-[fluorine-18] fluoro-D-glucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) as an alternative to technetium-99m and gallium-67 scans for diagnosis and assessment of response to treatment for patients with NEO. Case series. Tertiary referral center. From 2013 through 2017, 12 patients were diagnosed with NEO based on clinical features and positive FDG uptake within the temporal bone on PET/CT. Mean age was 74 ± 11.5; 83% of the patients were male; and 83% had diabetes. PET/CT scans were reviewed independently by two nuclear medicine specialists. Imaging located osteomyelitis in external ear canal, mastoid, temporomandibular joint, and nasopharyngeal region (100%, 50%, 16%, 8%, respectively). Mean follow-up was 16 months. Eight patients (67%) underwent a second PET/CT scan after active otitis resolved and after at least 6 weeks of antibiotic treatment. The scan demonstrated no or substantially reduced FDG uptake and treatment was stopped. The patients had no NEO symptoms at the end of follow-up. One patient had significant uptake, and antibiotic treatment was continued until a third scan demonstrated no FDG uptake. Two patients died before the second PET/CT, and two were lost to follow-up. 18F-FDG-PET/CT is a reliable imaging modality for diagnosis, disease localization, and decision making regarding treatment cessation. 18F-FDG-PET/CT should be considered as the imaging modality of choice for initial diagnosis and follow-up in NEO patients. Larger, controlled studies are warranted. 4 Laryngoscope, 129:961-966, 2019.

Occult stage IIIA-N2 patients have excellent overall survival with initial surgery.

Patients may be found to have stage IIIA-N2 at the final pathology after the initial surgery. We want to determine the survival rate in this unique group of patients. We reviewed all patients who underwent surgical resection for lung cancer from 2000 to 2011 who had pathologic stage N2 without induction therapy. We determined the clinicopathologic characteristics and survival rate in this unique group of patients. A total of 101 patients met the inclusion criteria. The average age of the group was 65 years old with 53 (53%) females. The chest computed tomography (CT) scans showed 30 patients (30%) with mediastinal lymphadenopathy (>1 cm) and 13 (13%) with multistation disease. The positron emission tomography-computed tomography (PET-CT) showed 24 patients (24%) with N2 positive uptake. Invasive mediastinal staging prior to surgery occurred in 43 patients (43%). Eighty-four patients underwent a lobectomy (83%), 7 with bilobectomy (7%), and 10 with pneumonectomy (10%). The most common pathology was adenocarcinoma with 73 patients (72%) and the second most common was squamous cell carcinoma with 22 patients (22%). Most of the patients completed the adjuvant chemoradiation therapy (86%). The 5-year survival rate was 48% and the 10-year survival rate was 24%. Pathologic stage IIIA-N2 non-small cell lung cancer (NSCLC) is a heterogeneous disease process with a very small group of patients undergoing initial surgery. Patients with occult stage IIIA-N2 who undergo initial surgery have an excellent overall survival rate.

Treatment Outcome, Toxicity, and Predictive Factors for Radioligand Therapy with 177Lu-PSMA-I&T in Metastatic Castration-resistant Prostate Cancer

Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is increasingly being used in metastatic castration-resistant prostate cancer (mCRPC). The objective of this study is to report our clinical experience with RLT using 177-lutetium–labeled PSMA-I&T. A total of 100 patients were treated under a compassionate use protocol with a total number of 319 cycles (median two cycles, range 1–6). Eligibility criteria included previous treatment with abiraterone or enzalutamide, previous taxane-based chemotherapy or chemoineligibility, and positive PSMA-ligand uptake at positron-emission tomography scan. The 177Lu-PSMA-I&T was given 6–8 weekly with an activity of 7.4 GBq up to six cycles. The median number of previous mCRPC regimens was 3 (range 1–6), and 35 patients had visceral metastases. Prostate-specific antigen decline of ≥50% was achieved in 38 patients, median clinical progression-free survival (cPFS) was 4.1mo, and median overall survival (OS) was 12.9mo. Subgroup analyses identified an association of visceral metastases with a poor prostate-specific antigen (PSA) response and shorter cPFS and OS, and an association of rising lactate dehydrogenase (LDH) with shorter cPFS and OS. Patients achieving PSA decline of ≥50% within 12wk of treatment showed longer cPFS and OS. Treatment-emergent hematologic grade 3/4 toxicities were anemia (9%), thrombocytopenia (4%), and neutropenia (6%). Grade 3/4 nonhematologic toxicities were not observed. RLT with 177Lu-PSMA-I&T showed good activity in more than one-third of patients with late-stage mCRPC at low toxicity. Presence of visceral metastases and rising LDH were associated with worse treatment outcome. Patient summaryWe analyzed the treatment outcome and toxicity of prostate-specific membrane antigen–targeted radioligand therapy in patients with metastatic castration-resistant prostate cancer. We found that a good treatment response could be achieved in a subgroup of patients with few side effects. We also observed that treatment outcome was worse in patients with organ metastases and elevated lactate dehydrogenase in blood tests.

Effectiveness of blended learning in the first year of fashion education

ABSTRACTFashion programmes have increased the use of e-learning and blended learning to enhance the levels of understanding of students on complex issues. The first year in higher education is important because it significantly affects future academic success and the completion rate of students. The effectiveness of blended learning for undergraduate students in their first year of study is explored by comparing the actual grades of students in a blended learning and in a traditional face-to-face classroom. Two first-year subjects, goal-setting and sewing, with blended learning activities are introduced. No significant difference exists in the actual grades of students who used the blended learning modules compared to the control group students. First-year fashion students are interested in blended learning with a positive uptake rate to enhance self-regulated learning. The diverse educational backgrounds of students and their prior learning experiences and needs must be considered to increase their engagement in online modules.

The role of bone SPECT/CT in patients with persistent or recurrent lumbar pain following lumbar spine stabilization surgery.

Despite recent advances in lumbar spine stabilization surgery (LSSS), a high number of patients continue to complain of persistent/recurrent lumbar pain after LSSS. Conventional imaging (plain radiography, CT and MRI) is commonly performed to assess potential lumbar pain generators, but findings are equivocal in approximately 20% of patients. The purpose of this study was to assess the diagnostic performance of 99mTc-HDP bone SPECT/CT in identifying potential pain generators in patients with persistent/recurrent lumbar pain after LSSS but in whom conventional diagnostic imaging is inconclusive. A total of 187 patients (median age 56years, 70 men) with persistent/recurrent lumbar pain following LSSS with inconclusive conventional imaging (plain radiography, CT and/or MRI) underwent 99mTc-HDP bone SPECT/CT and were included in the study. Tracer uptake on SPECT/CT, as an indicator of ongoing or altered osteoblastic activity, was assessed in the lumbar spine stabilization segment(s) and in adjacent segments. Uptake intensity was graded as (1) high (the same as or more than iliac crest uptake), (2) mild (the same as or more than nondiseased vertebral uptake but less than iliac crest uptake), or (3) negative (normal scan). Mild and high uptake were regarded as positive. In 160 of the 187 patients (85.6%), SPECT/CT showed positive mild or high tracer uptake in the LSSS region. More than half of the patients had abnormal tracer uptake in the stabilized segments (56.7%) and/or in the adjacent segments (55.6%). Although positive stabilized segment findings were commonly seen at <2years (70.3%) and the rate decreased with time after LSSS, they were seen at >6years after surgery in 38.2% of patients. In 51.4% of patients, abnormal activity was seen in the adjacent segments <2years after LSSS, suggesting early/accelerated degeneration after surgery. The proportion of patients with abnormal activity in the adjacent segments increased to 67.3% at >6years after LSSS (p< 0.05). Positive SPECT/CT findings in the stabilized segments were more frequent in patients with three or more stabilized segments (p< 0.05), but were not more frequent in the adjacent segments. Overall, positive SPECT/CT guided therapy in 64% of patients, which included facet joint/nerve root injections or re-do surgery at active sites and/or adjacent sites. Bone SPECT/CT is a sensitive diagnostic tool for identifying altered osteoblastic activity, which might be a pain generator in patients with persistent/recurrent pain after lumbar surgery especially when conventional imaging is inconclusive.

Sodium-fluoride PET-CT for the non-invasive evaluation of coronary plaques in symptomatic patients with coronary artery disease: a cross-correlation study with intravascular ultrasound

ObjectivesThe aim of this study was to evaluate the 18F-sodium fluoride (18F-NaF) coronary uptake compared to coronary intravascular ultrasound (IVUS) in patients with symptomatic coronary artery disease.Background18F-NaF PET enables the assessment of vascular osteogenesis by interaction with surface hydroxyapatite, while IVUS enables both identification and quantification of intra-plaque components.MethodsForty-four patients with symptomatic coronary artery disease were included in this prospective controlled trial, 32 of them (30 patients with unstable angina and 2 patients with stable angina), representing the final study cohort, got additional IVUS. All patients underwent cardiac 18F-NaF PET/CT and IVUS within 2 days. 18F-NaF maximum tissue-to-blood ratios (TBRmax) were calculated for 69 coronary plaques and correlated with IVUS plaque classification.ResultsSignificantly increased 18F-NaF uptake ratios were observed in fibrocalcific lesions (meanTBRmax = 1.42 ± 0.28), thin-cap atheroma with spotty calcifications (meanTBRmax = 1.32 ± 0.23), and thick-cap mixed atheroma (meanTBRmax = 1.28 ± 0.38), while fibrotic plaques showed no increased uptake (meanTBRmax = 0.96 ± 0.18). The 18F-NaF uptake ratio was consistently higher in atherosclerotic lesions with severe calcification (meanTBRmax = 1.34 ± 0.22). The regional 18F-NaF uptake was most likely localized in the border region of intensive calcification. Coronary lesions with positive 18F-NaF uptake showed some increased high-risk anatomical features on IVUS in comparison to 18F-NaF negative plaques. It included a significant severe plaque burden (70.1 ± 13.8 vs. 61.0 ± 13.8, p = 0.01) and positive remodeling index (1.03 ± 0.08 vs. 0.99 ± 0.07, p = 0.05), as well as a higher percentage of necrotic tissue (37.6 ± 13.3 vs. 29.3 ± 15.7, p = 0.02) in positive 18F-NaF lesions.Conclusions18F-NaF coronary uptake may provide a molecular insight for the characterization of coronary atherosclerotic lesions. Specific regional uptake is needed to be determined by histology.

Adoption and use of guidelines for whiplash: an audit of insurer and health professional practice in New South Wales, Australia

BackgroundIn Australia, the New South Wales (NSW) State Insurance Regulatory Authority has been continuously developing and implementing clinical practice guidelines to address the health and economic burden from whiplash associated disorders (WAD). Despite this, it is uncertain the extent to which the guidelines are followed. This study aimed to determine insurer and health professional compliance with recommendations of the 2014 NSW clinical practice guidelines for the management of acute WAD; and explore factors related to adherence.MethodsThis was an observational study involving an audit of 288 randomly-selected claimant files from 4 insurance providers in NSW, Australia between March and October 2016. Data extracted included demographic, claim and injury details, use of health services, and insurer and health professional practices related to the guidelines. Analyses involved descriptive statistics and correlation analysis.ResultsMedian time for general practitioner medical consultation was 4 days post-injury and 25 days for physical treatment (e.g. physiotherapy). Rates of x-ray investigations were low (21.5%) and most patients (90%) were given active treatments in line with the guideline recommendations. The frequency of other practices recommended by the guidelines suggested lower guideline adherence in some areas such as; using the Quebec Task Force classification (19.9%); not using specialised imaging for WAD grades I and II (e.g. MRI, 45.8%); not using routine passive treatments (e.g. manual therapy, 94.0%); and assessing risk of non-recovery using relevant prognostic tools (e.g. Neck Disability Index, 12.8%). Over half of the claimants (59.0%) were referred to other professionals at 9–12 weeks post-injury, among which 31.2% were to psychologists and 68.8% to specialists (surgical specialists, 43.6%; WAD specialists, 20.5%). Legal representation and lodgment of full claim were associated with increased number of medical visits and imaging (ρ 0.23 to 0.3; p < 0.01).ConclusionThere is evidence of positive uptake of some guideline recommendations by insurers and health professionals; however, there are practices that are not compliant and might lead to poor health outcomes and greater treatment cost. Organisational, regulatory and professional implementation strategies may be considered to change practice, improve scheme performance and ultimately improve outcomes for people with WAD.

18F-FDG PET/CT for therapeutic assessment in patients with bone metastases from differentiated thyroid carcinoma after 131I treatment

Objective To explore the value of 18F-fluorodeoxyglucose (FDG) PET/CT for therapeutic assessment in patients with bone metastases from differentiated thyroid carcinoma (DTC) after 131I treatment. Methods Between January 2006 and August 2017, 35 DTC patients (11 males, 24 females, median age 60 years) with bone metastases who were treated with 131I and underwent 18F-FDG PET/CT scan were retrospectively analyzed. Therapeutic response assessment was based on morphological changes or the maximum standardized uptake value (SUVmax) changes of bone metastases, and the agreement (Cohen′s Kappa coefficient) between two methods was analyzed. The progression-free survival (PFS) was estimated by Kaplan-Meier survival analysis and compared among patients with different treatment response (log-rank test). Results Morphological changes were consistent with SUVmax changes in 82.1%(23/28) of patients with positive 18F-FDG uptake (Kappa=0.731, 95% CI: 0.628-0.834, P<0.01). Five patients had stable disease according to morphological assessment, while 18F-FDG PET indicated they had metabolic response or disease progression. The serum thyroglobulin (Tg) levels confirmed the accuracy of 18F-FDG PET in 3 of those 5 patients. Compared with the patients with metabolically or morphologically progressive disease, patients who showed metabolically or morphologically stable disease or complete/partial response had significantly favorable prognosis (χ2 values: 4.132-6.543, all P<0.05). Conclusions The therapeutic response based on metabolic criteria is in agree with that based on morphological criteria in most of the DTC patients with bone metastases. The SUV may act as a sensitive and efficient indicator of early therapeutic response or disease progression of bone metastases in DTC patients with positive 18F-FDG uptake. Key words: Thyroid neoplasms; Neoplasm metastasis; Skeleton; Radiotherapy; Iodine radioisotopes; Positron-emission tomography; Tomography, X-ray computed; Deoxyglucose

Prevalence of wild type ATTR assessed as myocardial uptake in bone scan in the elderly population

BackgroundMyocardial uptake of bone tracers has emerged as useful tool for the early detection of transthyretin amyloidosis (ATTR). The prevalence of wild-type ATTR (ATTRwt) in individuals remains to be established. MethodsAll whole body bone scans performed in individuals ≥ 75 years with no previous clinical suspicion of ATTR were revised in a population-based university hospital over a 7-year period (1509 studies corresponding to 1114 patients; 80.5 ± 4.1 years, 65% males). Positive cardiac uptake was defined according to Perugini score as grade 2 or 3. Heart failure (HF) hospitalizations during the follow-up were obtained from regional administrative databases. ResultsThirty-one patients ≥ 75 years (2.78%) showed cardiac uptake; compared with those without uptake, these patients were older (85 ± 5 vs. 80 ± 4, p < 0.001) and predominantly males (90% vs. 64%, p = 0.005). The prevalence of cardiac uptake was 3.88% in males and 0.77% in females, and increased with age, reaching 13.9% in males≥85 years (2.7% among females). The estimated prevalence for the European standard population ≥ 75 years was 4.15% in males, 1.03% in females and 2.59% in the general population. HF hospitalizations rates were 14% in patients without uptake and 29% in those with cardiac uptake (p = 0.034). After adjusting for age and gender, cardiac uptake was associated with a higher risk of HF hospitalization (OR 2.60, 95%CI 1.09–5.74, p = 0.022). ConclusionsMyocardial uptake in bone scan is very prevalent with ageing, mainly affects males and is associated with an increased risk of HF hospitalization. These findings reinforce ATTRwt as a relevant cause of HF in the elderly.