Gastrointestinal radionuclide imaging in pediatric age group.

Pediatric gastrointestinal imaging plays a crucial role in evaluating and managing digestive system disorders in children. This comprehensive review dives into the nuances of pediatric gastrointestinal imaging techniques, focusing on three specific modalities: gastric emptying scintigraphy (GES), intestinal transit scintigraphy (ITS), and gastrointestinal bleeding scintigraphy. GES involves real-time monitoring of stomach emptying using radiotracers and gamma camera technology. While challenges exist in standardizing protocols due to age-specific meal compositions, GES remains pivotal in diagnosing motility disorders, gastroesophageal reflux, and abdominal pain in children. ITS, utilizing [67Ga], provides insights into gastrointestinal motility disorders such as Hirschsprung disease. It aids in whole-gut transit evaluation, guiding surgical interventions and improving long-term clinical outcomes. Gastrointestinal bleeding scintigraphy, employing [99mTc], assists in diagnosing conditions like Meckel's diverticulum and occult bleeding, offering continuous monitoring to pinpoint the bleeding site along the entire gastrointestinal tract. SPECT-CT improves the accuracy and the standards of care. Each technique's protocol details, clinical indications, and diagnostic capabilities are thoroughly discussed, highlighting the importance of these non-invasive, functional imaging modalities in pediatric gastroenterology.

GD2-CART01 for Relapsed or Refractory High-Risk Neuroblastoma.

BACKGROUND: Immunotherapy with chimeric antigen receptor (CAR)-expressing T cells that target the disialoganglioside GD2 expressed on tumor cells may be a therapeutic option for patients with high-risk neuroblastoma. METHODS: In an academic, phase 1-2 clinical trial, we enrolled patients (1 to 25 years of age) with relapsed or refractory, high-risk neuroblastoma in order to test autologous, third-generation GD2-CAR T cells expressing the inducible caspase 9 suicide gene (GD2-CART01). RESULTS: A total of 27 children with heavily pretreated neuroblastoma (12 with refractory disease, 14 with relapsed disease, and 1 with a complete response at the end of first-line therapy) were enrolled and received GD2-CART01. No failure to generate GD2-CART01 was observed. Three dose levels were tested (3-, 6-, and 10×106 CAR-positive T cells per kilogram of body weight) in the phase 1 portion of the trial, and no dose-limiting toxic effects were recorded; the recommended dose for the phase 2 portion of the trial was 10×106 CAR-positive T cells per kilogram. Cytokine release syndrome occurred in 20 of 27 patients (74%) and was mild in 19 of 20 (95%). In 1 patient, the suicide gene was activated, with rapid elimination of GD2-CART01. GD2-targeted CAR T cells expanded in vivo and were detectable in peripheral blood in 26 of 27 patients up to 30 months after infusion (median persistence, 3 months; range, 1 to 30). Seventeen children had a response to the treatment (overall response, 63%); 9 patients had a complete response, and 8 had a partial response. Among the patients who received the recommended dose, the 3-year overall survival and event-free survival were 60% and 36%, respectively. CONCLUSIONS: The use of GD2-CART01 was feasible and safe in treating high-risk neuroblastoma. Treatment-related toxic effects developed, and the activation of the suicide gene controlled side effects. GD2-CART01 may have a sustained antitumor effect. (Funded by the Italian Medicines Agency and others; ClinicalTrials.gov number, NCT03373097.).

Tandem high-dose 131I-MIBG therapy supported by dosimetry in pediatric patients with relapsed-refractory high-risk neuroblastoma: the Bambino Gesu' Children's Hospital experience.

OBJECTIVE: 131I-meta-iodobenzylguanidine (131I-MIBG) combined with myeloablative chemotherapy represents an effective treatment in children affected by relapsed/refractory neuroblastoma (NBL) for disease palliation and in improving progression-free survival. The aim of our study is to evaluate the feasibility, safety and efficacy of tandem 131I-MIBG followed by high-dose chemotherapy with Melphalan. METHODS: Thirteen patients (age range: 3-17 years) affected by relapsed/refractory NB, previously treated according to standard procedures, were included in the study. Each treatment cycle included two administrations of 131I-MIBG (with a dosimetric approach) followed by a single dose of Melphalan with peripheral blood stem cell rescue. RESULTS: At the end of the treatment, ten patients experienced grade 4 neutropenia, two grade 3 and one patient grade 2, three patients presented febrile neutropenia and all needed RBC and platelets transfusions; one patient presented grade 4 mucositis, four grade 3 and one patient grade 2 mucositis. One patient showed progressive disease, eight patients showed stable disease and four patients showed partial response. CONCLUSION: High-dose 131I-MIBG therapy combined with chemotherapy represent a well-tolerated and effective modality of treatment in heavily pretreated patients affected by relapsed/refractory NBL. However, further studies, including a wider cohort of patients, are needed.

Usefulness of iodine-123 whole-body scan in planning iodine-131 treatment of the differentiated thyroid carcinoma in children and adolescence.

OBJECTIVE: Radioiodine treatment (RAI-T) of differentiated thyroid carcinoma (DTC) is important to avoid disease progression, in particular in pediatric patients. For these reasons, a diagnostic scan may be useful to assess therapeutic tailored activity. The purpose of our study was to evaluate the usefulness of diagnostic whole-body scan (WBS) with iodine-123 (I) in combination with recombinant human thyroid-stimulating hormone (rh-TSH; Thyrogen) (rh-TSH-Dx-WBS), in planning RAI-T or further surgery before RAI-T in pediatric DTC. PATIENTS AND METHODS: Among 101 rh-TSH-Dx-WBS of 55 patients (21 males, mean age: 15 years, range: 5-18 years) followed at the Bambino Gesù Pediatric Hospital for DTC from February 2004 to December 2016, 41 rh-TSH-Dx-WBS scans of 41 patients (20 male and 21 female, mean age: 14 years, range: 5-18 years) performed for staging before RAI-T were retrospectively evaluated. Thyroglobulin was determined at baseline and on day 5. RESULTS: Receiver operating characteristic curve analysis showed that thyroglobulin alone is not a good predictor for staging modification (area under the curve=0.6855). rh-TSH-Dx-WBS showed both remnant and lymph node in 11 (27%), lymph node localization alone in one (2.5%), lung alone in 1/41 (2.5%), both lymph node and lungs in 2/41 (5%), and thyroid remnant alone in 26/41 (63%) patients. rh-TSH-Dx-WBS modified staging in 12/41 (29%): in 3/12 (25%) for the presence of lung metastases and in 9/12 (75%) for lymph node involvement. In all these patients, administered activity for RAI-T was then modified or further surgery was planned. CONCLUSION: Although further studies are needed, our data showed that combined use of rh-TSH and I-Dx-WBS allows an accurate and complete staging of disease, to implement the best therapeutic plan.

Role of three-phase bone scintigraphy in paediatric osteoid osteoma eligible for radiofrequency ablation.

OBJECTIVE: The objective of the study was to underline the importance of three-phase bone scintigraphy at the time of diagnosis in children with suspected osteoid osteoma (OO) who are eligible for radiofrequency ablation. METHODS: Fifty-three patients (13 girls; mean age 7.2 years, 20% younger than 10 years of age) who underwent bone scintigraphy for suspected OO between 2005 and 2010 were included in the study, of whom 46 underwent a radiography at diagnosis. Computed tomography-guided biopsy was performed in all patients after bone scintigraphy, and radiofrequency ablation was performed following biopsy in patients with OO; ablation efficacy was confirmed by MRI at 1, 3, 12 and 18 months. RESULTS: The radiographic results were negative in 27/46 patients and was unclear in 19. Bone scintigraphy showed lesions in 53/53 patients, of whom 51 patients had a typical pattern of osteoma and nine patients required an additional scan with a pinhole collimator. Histological examination showed OO in 51/53 patients (3/51 intramedullary), Ewing's sarcoma in 1/53 patients, and chronic osteomyelitis in 1/53 patients. CONCLUSION: Any child with recurrent nocturnal pain and/or limb swelling should undergo radiography of the involved skeletal segment, which is the first-choice diagnostic method in the clinical suspicion of OO. In the event of ambiguous or negative radiographic results, bone scintigraphy is needed to exclude other pathologic conditions and to confirm the diagnosis. In children with recurrent but not well-localized bone pain in which OO is strongly suspected for signs and symptoms, a bone scan can help detect the lesion. The diagnostic accuracy of the bone scan, particularly for the appendicular skeleton, can be improved by pinhole collimator acquisition.

Rhabdomyosarcoma associated hypertrophic osteoarthropathy in a child: detection by bone scintigraphy.

Hypertrophic osteoarthropathy (HOA) is characterized by digital clubbing, long bone periosteal reaction, and polyarthralgias. Primary familial HOA is very rare and is not associated with underlying disorders and has a good prognosis. Secondary pediatric nonneoplastic HOA is associated with cystic fibrosis, congenital heart disease, biliary atresia, and inflammatory bowel disease. Secondary neoplastic HOA may be associated with intra or extrathoracic tumors.A 5-year-old girl was admitted to our hospital for an abdominal mass, digital clubbing, and diffuse articular pain. The bone scan revealed symmetrical tracer uptake in the long bones. Upper and lower extremity x-rays were diagnostic for HOA. Paraneoplastic HOA in childhood accounts for not more than 12% of HOA paitents. HOA has been reported in 2 other cases of rhabdomyosarcoma.