Paediatric Horner Syndrome: How much further to investigate?

We report an infant with an early-onset Horner syndrome and normal urinary catecholamine levels. Further investigations with Nuclear medicine imaging with123I-MIBG (meta-iodo benzyl-guanidine) confirmed a right thoracic inlet mass consistent with a neuroblastoma, a tumor of neural crest origin. The authors emphasize the need for investigating idiopathic acquired pediatric Horner syndrome and the value of an MIBG scan as a diagnostic test for suspected neuroblastoma.

FDG PET-CT in pediatric Langerhans cell histiocytosis.

OBJECTIVE: Langerhans cell histiocytosis (LCH) in pediatric patients presents with single-system or multisystem disease. Accurate staging is essential for selecting the most appropriate therapy ranging from local surgery to chemotherapy. METHODS: A retrospective review was undertaken of reported fludeoxyglucose (FDG) positron emission tomography - computed tomography (PET-CT) scans performed in children with LCH from June 2006 to February 2017. Findings were compared with a reference standard of biopsy or informed clinical follow-up. RESULTS: One hundred nine scans were performed in 33 patients (age 7 weeks to 18 years). Nineteen patients had single-system, bone unifocal disease; seven patients had single-system, bone multifocal disease; four patients had single-system, skin unifocal disease; two patients had multisystem disease; and one patient had single-system, lymph node disease. Twenty-six scans were performed to stage biopsy-proven LCH, and 83 scans were performed during follow-up to assess treatment response or recurrence after therapy completion. At staging, FDG PET-CT detected all sites of biopsy-proven LCH (except where bone unifocal disease had been resected). There was one false-positive thymic finding that resolved without therapy. The per-patient false-positive rate of FDG PET-CT at staging was 4% (1/26). During follow-up, five LCH recurrences and one case of progressive disease on therapy occurred, all positive on FDG PET-CT. During follow-up two patients had FDG PET-CT scans with false-positive findings and one patient with a magnetic resonance imaging false-positive finding. The per-scan false-positive rate of FDG PET-CT during follow-up was 2% (2/83). CONCLUSIONS: FDG PET-CT is highly sensitive for the staging and follow-up of pediatric patients with LCH, and has a very low false-positive rate.

Imaging sentinel lymph nodes.

As the technique of sentinel lymph node (SLN) biopsy has evolved over the last 22 years, it has become increasingly evident that accurate SLN imaging is vital to allow surgical removal of only the true SLN(s) and not other nodes. Identifying the lymphatic collectors draining a tumor site and following them to the draining SLNs defines which nodes need to be removed for careful histologic examination. Current technology allows the exact location of each SLN to be defined. This allows the full benefits of SLN biopsy to be achieved, that is, highly accurate lymph node staging with minimal morbidity. In melanoma and breast cancer, the current practice of preoperative lymphoscintigraphy (LS) using peritumoral injections of tracer or injection adjacent to an excision biopsy site with dynamic imaging to visualize the lymphatic collectors and delayed imaging including single-photon emission computed tomography/computed tomography gives the best results. This information informs the surgical approach and allows rapid excision of the SLNs at surgery.In patients with visceral tumors where the primary cancer site is difficult to access, it appears that using fluorophores that are fluorescent under near-infrared light, injected during surgery, is evolving as the preferred technique.

Voxel-based analysis of normal cerebral [18F]FDG uptake during childhood using statistical parametric mapping.

The changing pattern of relative cerebral (18)F-fluoro-2-deoxy-D-glucose (FDG) uptake that occurs during normal childhood development is not completely understood. Using SPM8 we undertook a voxel-based analysis of dedicated cerebral FDG scans in 28 children ranging in age from 11 months to 16 years to examine the effects of age on regional FDG uptake. The subjects included were children with suspected or proven extracranial malignancies without central nervous system metastases and no previous or current therapies or medical conditions likely to interfere with cerebral metabolism. The included cerebral FDG scans were considered to represent normal cerebral FDG distribution in a child of their age at the time of the scan. When normalised to whole brain mean uptake, the voxel-based analysis showed increasing FDG uptake with age in the premotor and prefrontal cortices, insula cortex, cingulate cortex, basal ganglia, thalamus, cerebellum and in small areas of the inferior temporal lobes and left Heschl's gyrus. These findings correlate with previous published analysis of the same data that used qualitative and maximal standardised uptake value (SUV(max)) analysis techniques. This data provides more regionally specific information and further supports the conclusion that relative cerebral FDG uptake in children has not reached a typical adult pattern by approximately one year of age but in fact changes throughout childhood. The results speak to the importance of using age-matched data or adjusting for age in the statistical analysis of studies comparing paediatric cerebral FDG scans to a control dataset to avoid bias due to different age distributions in the groups of subjects studied. The areas of increasing FDG uptake with age probably relate to underlying neuronal processes linked to normal neurodevelopment including key resting state networks.

Normal cerebral FDG uptake during childhood.

PURPOSE: Current understanding of cerebral FDG uptake during childhood originates from a small number of studies in patients with neurological abnormalities. Our aim was to describe cerebral FDG uptake in a dataset of FDG PET scans in children more likely to represent a normal population. METHODS: We reviewed cerebral FDG PET scans in children up to 16 years of age with suspected/proven extracranial malignancies and the following exclusions: central nervous system metastases, previous malignancies, previous chemotherapy or radiotherapy, development of cerebral metastases during therapy, neurological conditions, taking antiepileptic medication or medications likely to interfere with cerebral metabolism, and general anaesthesia within 24 h. White matter, basal ganglia, thalamus and the cerebellar cortex were analysed using regional SUV(max), and the cerebral cortex, basal ganglia, thalamus and cerebellum were analysed using a regional relative uptake analysis in comparison to maximal cortical uptake. RESULTS: Scans from 30 patients (age range 11 months to 16 years, mean age 10 years 5 months) were included. All regions showed increasing SUV(max) with age. The parietal, occipital, lateral temporal and medial temporal lobes showed lower rates of increasing FDG uptake causing changing patterns of regional FDG uptake during childhood. The cortical regions showing the most intense uptake in early childhood were the parietal and occipital lobes. At approximately 7 years of age these regions had relatively less uptake than the frontal lobes and at approximately 10 years of age these regions had relatively less uptake than the thalamus. CONCLUSION: Relative FDG uptake in the brain has not reached an adult pattern by 1 year of age, but continues to change up to 16 years of age. The changing pattern is due to different regional rates of increasing cortical FDG uptake, which is less rapid in the parietal, occipital and temporal lobes than in the frontal lobes.

18F-FDG PET/CT compared to conventional imaging modalities in pediatric primary bone tumors.

BACKGROUND: F-Fluoro-2-deoxy-D: -glucose (FDG) positron emission tomography (PET) is useful in adults with primary bone tumors. Limited published data exist in children. OBJECTIVE: To compare hybrid FDG positron emission tomography/computed tomography (PET/CT) with conventional imaging (CI) modalities in detecting malignant lesions, predicting response to chemotherapy and diagnosing physeal involvement in pediatric primary bone tumors. MATERIALS AND METHODS: Retrospective analysis of PET/CT and CI reports with histopathology or follow-up > 6 months as reference standard. Response parameters and physeal involvement at diagnosis were compared to histopathology. RESULTS: A total of 314 lesions were detected in 86 scans. Excluding lung lesions, PET/CT had higher sensitivity and specificity than CI (83%, 98% and 78%, 97%, respectively). In lung lesions, PET/CT had higher specificity than CI (96% compared to 87%) but lower sensitivity (80% compared to 93%). Higher initial SUV(max) and greater SUV(max) reduction on PET/CT after chemotherapy predicted a good response. Change in tumor size on MRI did not predict response. Both PET/CT and MRI were very sensitive but of low specificity in predicting physeal tumor involvement. CONCLUSION: PET/CT appears more accurate than CI in detecting malignant lesions in childhood primary bone tumors, excluding lung lesions. It seems better than MRI at predicting tumor response to chemotherapy.

Extrarenal malignant rhabdoid tumor in childhood application of 18F-FDG PET/CT.

Extrarenal malignant rhabdoid tumor (MRT) is a rare malignancy in childhood and has a poor prognosis. Accurate histopathologic diagnosis and staging of the malignancy has major implications for patient management. The application of F-fluoro-deoxy-glucose positron emission tomography/computed tomography (F-FDG PET/CT) in pediatric malignancy has been well described and is having a significant clinical impact in many common pediatric cancers, in particular lymphoma, brain tumors, bone and soft tissue sarcomas. The use of PET/CT using F-FDG in rare tumors such as MRT is unclear. Two cases of MRT in childhood are described. One patient, a 12-year-old female, was shown to have extensive metastatic disease on PET/CT, showed poor response to chemotherapy and progression of disease detected on PET/CT. Her management was changed to palliative care. The second child, a 20-month-old female, presented with a parapharyngeal mass. The initial magnetic resonance imaging showed the mass and possible metastatic ipsilateral cervical lymph nodes. The initial staging PET/CT confirmed avid metabolic activity in the tumor and regional node involvement but no distant metastases. She showed an initial good but incomplete response on PET/CT and magnetic resonance imaging to chemotherapy and her treatment program was changed. The patient relapsed with recurrent pharyngeal tumor and her management was changed to palliative care. MRT accumulate F-FDG avidly. PET/CT was helpful in the initial staging, assessing response to treatment, and in clinical decisions at various stages of management for both patients.

Guidelines for lymphoscintigraphy and F18 FDG PET scans in melanoma.

Melanoma has a high potential to develop metastases. Accurate staging is essential for appropriate management. Sentinel node (SN) status is a powerful prognostic factor in early stage melanoma. Staging is assisted by SN biopsy after lymphoscintigraphy to locate all true SNs prior to biopsy. PET using F18-FDG can detect metastases and is used to restage patients with AJCC Stages III and IV disease before planning surgery with curative intent.

Potential use of 68Ga-apo-transferrin as a PET imaging agent for detecting Staphylococcus aureus infection.

INTRODUCTION: (67)Ga citrate has been extensively used to detect infection and inflammation since 1971. However, its clinical utility is compromised due to several limitations. The present project explored whether (68)Ga-apo-transferrin ((68)Ga-TF), when prepared in vitro, is a useful agent for positron emission tomography (PET) imaging of bacterial infection. METHODS: An infection was induced in male Wistar rats by injecting 5 × 10(5) CFU units of Staphyococcus aureus in the right thigh muscle. (68)Ga-TF was synthesized by mixing (68)GaCl(3) with apo-transferrin (TF, 2 mg) in sodium carbonate (0.1 M, pH 7.0) and incubating at 40 °C for 1 h. Animals were injected with 10-15 MBq of (68)Ga-TF containing approximately 0.2 mg TF and imaged at different time intervals using Siemens Biograph PET-CT. RESULTS: When (68)Ga-TF were injected in the infected rats, the infection lesion was detectable within 20 min post injection. The biodistribution showed the uptake at the lesion increased with time as shown by significantly increased standard uptake values for up to 4 h post injection. There was a considerable decrease in the background activity during the same period of study, giving higher target-to-muscle ratios. Blood pool activity at 3 h post injection was insignificant. (68)GaCl(3) (when not conjugated to TF) did not localize at the infection lesion up to 120 min post injection. CONCLUSION: The preliminary results suggest that (68)Ga-TF is capable of detecting S. aureus infection in the rat model, within an hour after intravenous injection.

18F-FDG PET/CT in paediatric lymphoma: comparison with conventional imaging.

PURPOSE: In children with Hodgkin's disease and non-Hodgkin's lymphoma, the ability of (18)F-fluoro-2-deoxy-D-glucose PET/CT and conventional imaging (CI) to detect malignant lesions and predict poor lesion response to therapy was assessed and compared. METHODS: A retrospective review of findings reported on PET/CT and CI was performed using a lesion-based analysis of 16 lymph node and 8 extra-nodal regions. Lesions were defined by histopathological findings or follow-up > 6 months. RESULTS: The study included 209 PET/CT scans with a valid CI comparator. A total of 5,014 regions (3,342 lymph node, 1,672 extra-nodal) were analysed. PET/CT performed significantly better than CI in the detection of malignant lesions with sensitivity and specificity of 95.9 and 99.7% compared to 70.1 and 99.0%, respectively. For predicting poor lesion response to therapy, PET/CT had fewer false-positive lesions than CI. The specificity for predicting poor lesion response to treatment for PET/CT was 99.2% compared to 96.9% for CI. PET/CT was the correct modality in 86% of lesions with discordant findings. CONCLUSION: PET/CT is more accurate than CI in detecting malignant lesions in childhood lymphoma and in predicting poor lesion response to treatment. In lesions with discordant findings, PET/CT results are more likely to be correct.

High grade primary vesicoureteral reflux in boys: long-term results of a prospective cohort study.

PURPOSE: We evaluated the incidence of new permanent defects in boys with grade 4 or 5 vesicoureteral reflux, identified the risk factors for new permanent defects and reviewed the outcome of different management approaches by assessing the rates of urinary tract infection and new permanent defects. MATERIALS AND METHODS: This prospective cohort study recruited patients from July 1995 to December 2006. Study inclusion criteria were male gender and grade 4 or 5 primary vesicoureteral reflux. Patients were divided into 2 groups by presentation mode, including group 1-prenatal reflux diagnosis and group 2-reflux diagnosed after investigation for urinary tract infection. All patients underwent initial renal (99m)Tc-dimercapto-succinic acid scan evaluation. Continuous antibiotic prophylaxis was given in all patients until at least age 2 years. Surgical correction for reflux was done in 28 patients and 76 were circumcised. Followup included renal (99m)Tc-dimercapto-succinic acid scan with renal ultrasound at age 12 months with repeat (99m)Tc-dimercapto-succinic acid scan at ages 2 and 4 years. RESULTS: Included in our study were 151 patients (206 high grade refluxing renal units) with a median age at diagnosis of 1.9 months (range 1 day to 8.8 years). Median age at first followup was 14 months (range 3 months to 3 years) and at next followup it was 39 months (range 10 months to 11.3 years). There were 52 boys (34%) in group 1 and 99 (66%) in group 2. Baseline perfusion defects on initial renal (99m)Tc-dimercapto-succinic acid scan were identified in 41 of 52 boys (78.8%) in group 1 and in 74 of 99 (74.7%) in group 2. During followup new permanent defects developed in 8 of 52 boys (15%) in group 1 and in 10 of 99 (10%) in group 2. In 18 patients a total of 20 renal units showed new permanent defects, including 13 in kidneys with baseline perfusion defects and 7 in previously normal kidneys (p >0.9). In groups 1 and 2 combined infection developed before and after circumcision in 62 of 137 (45.2%) and 5 of 74 cases (6.7%), respectively (p <0.001). New permanent defects were seen in 4 of 76 circumcised (5.2%) and in 14 of 137 uncircumcised boys (10.2%) (p >0.3). CONCLUSIONS: Baseline perfusion defects were seen on (99m)Tc-dimercapto-succinic acid scan at presentation in 115 of our 151 patients (76%) independent of presentation mode. New permanent defects developed in abnormal and previously normal kidneys, and were associated with urinary tract infection. Being circumcised was associated with fewer urinary tract infections and a lower incidence of observed new permanent defects (5.2% vs 10.2%).

Cortical hypometabolism demonstrated by PET in relapsing NMDA receptor encephalitis.

N-methyl-d-aspartate (NMDA) receptor encephalitis is a newly defined type of autoimmune encephalitis. Two girls (age 3 years, case 1, and 7 years, case 2) with relapsing NMDA receptor encephalitis each had the classic clinical features of encephalopathy, movement disorders, psychiatric symptoms, seizures, insomnia, and mild autonomic dysfunction. Both patients had persistent neuropsychiatric disability, despite immune therapies. Positron emission tomography (PET) scans were performed during clinical relapse at 6 weeks (case 1) and 5 months (case 2). In both cases, the scans demonstrated reduced fluorodeoxyglucose metabolism in the cerebral cortex, with the temporal regions being most affected. PET imaging was more sensitive than magnetic resonance imaging in these patients. In contrast, the one previous report of acute NMDA receptor encephalitis indicated cortical hypermetabolism. Thus, NMDA receptor encephalitis may be associated with variable PET findings, possibly dependent upon the timing of the study, or other factors. Future studies should investigate whether cortical hypometabolism is associated with a relapsing course, and whether it is predictive of a poorer outcome in NMDA receptor encephalitis.

Utility of positron emission tomography for tumour surveillance in children with neurofibromatosis type 1.

PURPOSE: There is little consensus regarding optimal surveillance of optic pathway glioma (OPG) and plexiform neurofibroma (PNF) in childhood neurofibromatosis type 1 (NF1). (18)F-2-Fluoro-2-deoxy-D: -glucose (FDG) positron emission tomography and computed tomography (PET/CT) is employed in the surveillance of adult PNFs; but its utility has neither been specifically studied in children with PNFs nor in children with OPG. METHODS: Review of PET/CT studies was performed in NF1 children with OPG or PNF. FDG-avidity of tumours was semi-quantitatively analysed and graded by calculating the maximum standardised uptake value (SUV(max)) [grade 1: <3 (low), grade 2: >3-<4 (intermediate), grade 3: >4 (intense)]. RESULTS: Eighteen children (ten girls; median age: 8.5-years) had PET/CT. Nineteen OPGs were imaged. The SUV(max) could be measured in 16. Ten were grade 1 and three each were grade 2 and grade 3. FDG-avidity reduced from grade 3 to grade 1 in two symptomatic OPGs following chemotherapy and this was associated with clinical improvement. PET/CT diagnosed symptomatic OPGs with a sensitivity of 0.625 [95% confidence interval (CI): 0.259-0.897] and specificity of 0.875 (95% CI: 0.466-0.993). Sixteen PNFs were imaged. Twelve were grade 1 and two each were grade 2 and grade 3. The two grade 3 PNFs were confirmed malignant peripheral nerve sheath tumours. PET/CT diagnosed malignant transformation with a sensitivity of 1.0 (95% CI: 0.197-1.0) and specificity of 0.857 (95% CI: 0.561-0.974). CONCLUSION: PET/CT may contribute useful information to the surveillance of OPG in childhood NF1-particularly to identify progressive, symptomatic tumours. As in adults, PET/CT is useful for the detection of malignant transformation in PNFs in children with NF1.

Sentinel lymph node biopsy in pediatric and adolescent cutaneous melanoma patients.

BACKGROUND: The rarity of melanoma in young patients, particularly pediatric ones, has to date precluded any valid comparisons being made between young patients and adults undergoing sentinel lymph node biopsy (SLNB) for intermediate thickness localized melanoma. The present study takes advantage of the large Sydney Melanoma Unit (SMU) database to clarify this issue. MATERIALS AND METHODS: Clinical and pathologic data on pediatric and adolescent AJCC Stage I and II cutaneous melanoma patients aged <20 years undergoing SLNB at the SMU between January 1993 and February 2008 were reviewed. SLNB positivity rates and outcomes in these patients were compared with adult SMU patients. RESULTS: In 55 young patients, overall median tumor thickness was 1.7 mm (range, 0.6-5.2 mm) and overall SLNB positivity rate was 14 of 55 (25%), tumors tending to be thicker (median, 2.6 mm), and SLNB positivity rate higher (2 of 6; 33%) in patients aged <10 years. Of the 14 patients, 13 underwent immediate completion lymph node dissection (CLND); 2 patients had non-SLN metastases (15.4%). Only 0.7% of a total of 295 lymph nodes removed at CLND were involved with melanoma. In 14 SLNB-positive patients with follow-up data, 3 (21%) have died from melanoma after a median follow-up of 60 months, compared with 42% of 356 SLNB positive adults. CONCLUSIONS: Although the SLNB positivity rate was higher in pediatric and adolescent melanoma patients than in adults (25% vs. 17%, respectively), non-SLN positivity and melanoma-specific death rates were low.

Hepatobiliary scintigraphy for the assessment of biliary strictures after pediatric liver transplantation.

HBS is used in the management of liver transplantation, a significant complication of which is biliary stricture. Strictures may be intraparenchymal within segments and main duct (non-anastomotic) or at the biliary-enteric anastomosis (anastomotic). Strictures are definitively diagnosed, and often managed, by PTC. This is invasive, technically challenging, and requires general anesthesia in young children. HBS may allow early detection of these complications and is non-invasive. The aim of this study was to review the scintigraphic pattern of biliary strictures using (99m)TcDISIDA HBS following pediatric orthotopic liver transplantation, and to assess its role in the diagnostic algorithm of suspected biliary strictures. All available hepatobiliary studies performed post-transplant in 101 episodes of liver transplantation in 92 pediatric patients were reviewed. Twenty-three (23%) patients had known biliary strictures. Twenty-two patients had adequate studies available for review; five had intrahepatic (non-anastomotic) strictures alone, nine had a stricture of the anastomosis alone, and eight had both intrahepatic and anastomotic strictures. HBS patterns (either segmental or global changes) correlated very highly with clinically significant biliary strictures. All patients with known strictures had abnormal HBS; hence, in patients with abnormal liver function tests post-liver transplant, a normal HBS makes strictures very unlikely. We propose that HBS can thus be used to determine if further investigation is required.

Imaging of therapy-induced apoptosis using (99m)Tc-HYNIC-annexin V in thymoma tumor-bearing mice.

The primary focus of this study was to assess the potential of (99m)Tc-HYNIC-Annexin V for in vivo imaging of apoptosis after systemic chemotherapy and "more localized" radiotherapy in nude mice bearing thymoma tumors and correlating it with TUNEL staining. (99m)Tc-HYNIC-Annexin V was administered intravenously to tumor-bearing mice (n = 25) before and after therapy. Mice were then imaged at 4 hours postinjection, and the animals were subsequently sacrificed. Tumor uptake increased significantly in response to treatment [chemotherapy (n = 8): 1.80 +/- 0.52 %ID/g, p < 0.009; radiotherapy (n = 7): 0.81 +/- 0.07 %ID/g, p < 0.02], compared to the control group (n = 10) (0.57 +/- 0.05 %ID/g). Tumor-to-muscle (T:M) and tumor-to-blood (T:B) ratios were significantly higher in both chemotherapy-treated (p < 0.02 and p < 0.01) and radiotherapy-treated cohorts (p < 0.05 and p < 0.03), compared to the control cohorts at 4 hours postinjection of (99m)Tc-Annxin V. In the post-therapy cohorts, the immunohistochemistry studies indicated a statistically significant correlation between tumor uptake of (99m)Tc-HYNIC-Annexin V and the extent of apoptosis detected by TUNEL-positive staining (r(2) = 0.41). The physiologic localization of the agent was found mainly in the kidneys (34%), liver (11%), and urine (22%). The results suggest that (99m)Tc-HYNIC-Annexin V may be an ideal agent for imaging apoptosis in response to treatment in a thymoma tumor bearing mouse model.

Case report: consumptive hypothyroidism consequent to multiple infantile hepatic haemangiomas.

A 10-month-old infant with multiple infantile hepatic hemangiomas and developmental delay is reported. He was found to be profoundly hypothyroid. Evaluation and management issues are discussed. This case emphasizes the importance of screening for hypothyroidism in patients with hemangiomas and the potential therapeutic benefit of prednisolone therapy in this condition.

Ga-67 and CT fusion imaging of an infected aortic graft.

A 17-year-old girl with a background of aortic coarctation repaired with insertion of a prosthetic graft presented with persisting fever and nonspecific back pain. Whole body Ga-67 scintigraphy was performed to evaluate occult infection. Intense uptake was noted in the region of the superior mediastinum. Fusing Ga-67 tomographic reconstruction with CT images allowed accurate determination of the area of enhanced uptake to be at the site of the aortic graft.