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.

Prognostic factors in children and adolescents with differentiated thyroid carcinoma treated with total thyroidectomy and RAI: a real-life multicentric study.

PURPOSE: This multicentric study aimed to investigate the main prognostic factors associated with treatment response at 1 year after radioactive iodine therapy (RAIT) and the last disease status in pediatric patients affected by differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: In the period 1990-2020, all consecutive patients ≤ 18 years from six different centers were retrospectively included. Patients were classified as low, intermediate, and high risk for persistence/recurrence. The response to RAIT was evaluated and scored 1 year later according to 2015 ATA guidelines. Moreover, at the last follow-up, the disease status was evaluated and dichotomized as no evidence of disease (NED) or persistent disease. RESULTS: Two hundred and eighty-five patients (197 female, 88 male; mean age 14.4 years) were recruited. All, except nine, underwent near-total thyroidectomy followed by RAIT. One-year after first RAIT, 146/276 (53%) patients had excellent response, 37/276 (14%) indeterminate response, and 91/276 (33%) incomplete response. One-year after RAIT, children with excellent response had significantly lower stimulated thyroglobulin (sTg) compared to not excellent group (median sTg 4.4 ng/ml vs 52.5 ng/ml, p < 0.001). ROC curve showed sTg higher than 27.2 ng/ml as the most accurate to predict 1-year treatment response. After a median follow-up of 133 months, NED was present in 241 cases (87%) while persistent disease in 35 (13%). At multivariate analysis, sTg and 1-year treatment response categories were both significantly associated with the last disease status (p value 0.023 and < 0.001). CONCLUSIONS: In pediatric DTC, sTg is significantly associated with 1-year treatment response and final outcome. However, 1-year response is the principal prognostic factor able to predict pediatric DTCs outcome.

Focal congenital hyperinsulinism managed by medical treatment: a diagnostic algorithm based on molecular genetic screening.

OBJECTIVE: Congenital hyperinsulinism (CHI) requires rapid diagnosis and treatment to avoid irreversible neurological sequelae due to hypoglycaemia. Aetiological diagnosis is instrumental in directing the appropriate therapy. Current diagnostic algorithms provide a complete set of diagnostic tools including (i) biochemical assays, (ii) genetic facility and (iii) state-of-the-art imaging. They consider the response to a therapeutic diazoxide trial an early, crucial step before proceeding (or not) to specific genetic testing and eventually imaging, aimed at distinguishing diffuse vs focal CHI. However, interpretation of the diazoxide test is not trivial and can vary between research groups, which may lead to inappropriate decisions. Objective of this report is proposing a new algorithm in which early genetic screening, rather than diazoxide trial, dictates subsequent clinical decisions. PATIENTS, METHODS AND RESULTS: Two CHI patients weaned from parenteral glucose infusion and glucagon after starting diazoxide. No hypoglycaemia was registered during a 72-h continuous glucose monitoring (CGMS), or hypoglycaemic episodes were present for no longer than 3% of 72-h. Normoglycaemia was obtained by low-medium dose diazoxide combined with frequent carbohydrate feeds for several years. We identified monoallelic, paternally inherited mutations in KATP channel genes, and (18) F-DOPA PET-CT revealed a focal lesion that was surgically resected, resulting in complete remission of hypoglycaemia. CONCLUSIONS: Although rare, some patients with focal lesions may be responsive to diazoxide. As a consequence, we propose an algorithm that is not based on a 'formal' diazoxide response but on genetic testing, in which patients carrying paternally inherited ABCC8 or KCNJ11 mutations should always be subjected to (18) F-DOPA PET-CT.

Fit of biokinetic data in molecular radiotherapy: a machine learning approach.

BACKGROUND: In literature are reported different analytical methods (AM) to choose the proper fit model and to fit data of the time-activity curve (TAC). On the other hand, Machine Learning algorithms (ML) are increasingly used for both classification and regression tasks. The aim of this work was to investigate the possibility of employing ML both to classify the most appropriate fit model and to predict the area under the curve (τ). METHODS: Two different ML systems have been developed for classifying the fit model and to predict the biokinetic parameters. The two systems were trained and tested with synthetic TACs simulating a whole-body Fraction Injected Activity for patients affected by metastatic Differentiated Thyroid Carcinoma, administered with [131I]I-NaI. Test performances, defined as classification accuracy (CA) and percentage difference between the actual and the estimated area under the curve (Δτ), were compared with those obtained using AM varying the number of points (N) of the TACs. A comparison between AM and ML were performed using data of 20 real patients. RESULTS: As N varies, CA remains constant for ML (about 98%), while it improves for F-test (from 62 to 92%) and AICc (from 50 to 92%), as N increases. With AM, [Formula: see text] can reach down to - 67%, while using ML [Formula: see text] ranges within ± 25%. Using real TACs, there is a good agreement between τ obtained with ML system and AM. CONCLUSIONS: The employing of ML systems may be feasible, having both a better classification and a better estimation of biokinetic parameters.

Congenital Hyperinsulinism of a Large Italian Cohort: A Retrospective Study.

INTRODUCTION: To evaluate and describe the diagnostic process, medical, nutritional, and surgical approach, and neurological outcome, we report data from a large Italian cohort of patients with congenital hyperinsulinism (CHI). METHODS: We retrospectively analyzed 154 CHI patients admitted to Ospedale Pediatrico Bambino Gesù from 1985 to 2022. RESULTS: Hypoglycemia occurred within the first year of life in 85.5% of patients, median time to diagnosis was 1 day (IQR 14 days). Ninety-two percent of patients were treated with diazoxide: 66.9% were responsive. Octreotide was administered to 28.6% of patients: 61.4% were responsive. Forty percent of patients were off-therapy, mostly from diazoxide. Thirty-four percent of patients carried mutations in ABCC8, 12.6% were syndromic, and 9.2% were transient CHI. Surgery was performed in 23/47 diazoxide-unresponsive and 2/95 diazoxide-responsive patients: 64.0% were focal at histology. Combining data from genetics, pancreatic venous sampling, 18F-DOPA PET/CT, and histology, 80.6% resulted diffuse, 16.7% focal, and 2.8% atypical CHI. Post-surgical diabetes developed in 6 patients. Neurocognitive evaluation revealed developmental delay or intellectual disability in 15.7% of 70 patients, mostly of a mild degree. Epilepsy was documented in 13.7% of 139 patients. CONCLUSION: Our diagnostic and therapeutic results are mainly consistent with the international indications and the CHI Global Registry data, with relatively low rates of neurological outcomes. Good outcomes were likely associated with early diagnosis and prompt management of patients because the majority of patients were diagnosed within 2 weeks. Remarkably, it is of utmost importance to spread the knowledge and refer CHI patients to multidisciplinary expert centers.

Myocardial Functional Imaging in Pediatric Nuclear Cardiology.

The role of nuclear medicine in pediatric cardiology has grown rapidly over the years, providing useful functional and prognostic information and playing a complementary role to morphological imaging in the evaluation of myocardial perfusion, cardiovascular inflammation and infections, and cardiac sympathetic innervation. The aim of this narrative review is to summarize and highlight the most important evidence on pediatric nuclear cardiology, describing clinical applications and the possibilities, advantages, and limitations of nuclear medicine techniques. Moreover, a special focus will be given to the minimization of radiation exposure in pediatric nuclear cardiology imaging, a critical topic in children.

Case report: Pylorus-preserving pancreatoduodenectomy for focal congenital hyperinsulinism in a 5-month-old baby.

Background: In focal congenital hyperinsulinism (CHI), surgery is the gold standard of treatment, even for lesions localized in the head of the pancreas. We report the video of the pylorus-preserving pancreatoduodenectomy performed in a five-month-old child with focal CHI. Operative technique: Baby was placed in the supine position with both arms outstretched to the up. After transverse supraumbilical incision and mobilization of ascending and transverse colon, exploration and multiple biopsies of the tail and the body of the pancreas ruled out multifocality. Pylorus-preserving pancreatoduodenectomy was performed according to the following steps: extended Kocher maneuver, followed by retrograde cholecystectomy and common bile duct isolation; division of the gastroduodenal artery and of the gastrocolic ligament; division of the duodenum, Treitz ligament and jejunum; transection of the pancreatic body. The reconstructive time was with: pancreato-jejunostomy; hepaticojejunostomy; pilorus-preserving antecolic duodeno-jejunostomy. The anastomoses were accomplished with synthetic absorbable monofilament sutures; two drains were placed close to the biliary and pancreatic anastomoses and to the intestinal anastomosis, respectively. Total operative time was 6 h, with no blood loss and/or intra-operative complications, immediate normalization of blood glucose levels and discharge from surgical ward 19 days after surgery. Conclusions: Surgical treatment of medical unresponsive focal forms of CHI is feasible in very small children: it is mandatory to refer the baby to a high-volume centre for a multidisciplinary management involving hepato-bilio-pancreatic surgeons and experts in metabolic disease.

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.

Personalized dosimetry for a deeper understanding of metastatic response to high activity 131I-mIBG therapy in high risk relapsed refractory neuroblastoma.

BACKGROUND: Dosimetry in molecular radiotherapy for personalized treatment is assuming a central role in clinical management of aggressive/relapsed tumors. Relapsed/refractory metastatic high-risk neuroblastoma (rrmHR-NBL) has a poor prognosis and high-activity 131I-mIBG therapy could represent a promising strategy. The primary aim of this case series study was to report the absorbed doses to whole-body (DWB ), red marrow (DRM ) and lesions (DLesion ). A secondary aim was to correlate DLesion values to clinical outcome. METHODS: Fourteen patients affected by rrmHR-NBL were treated with high-activity 131I-mIBG therapy (two administrations separated by 15 days). The first administration was weight-based whereas the second one was dosimetry-based (achieving DWB equals to 4 Gy). In all patients DWB and DRM was assessed; 9/14 patients were selected for DLesion evaluation using planar dosimetric approach (13 lesions evaluated). Treatment response was classified as progressive and stable disease (PD and SD), partial and complete response (PR and CR) according to the International Neuroblastoma Response Criteria. Patients were divided into two groups: Responder (CR, PR, SD) and Non-Responder (PD), correlating treatment response to DLesion value. RESULTS: The cumulative DWB , DRM and DLesion ranged from (1.5; 4.5), (1.0; 2.6) and (44.2; 585.8) Gy. A linear correlation between DWB and DRM and a power law correlation between the absorbed dose to WB normalized for administered activity and the mass of the patient were observed. After treatment 3, 2, 4 and 5 patients showed CR, PR, SD and PD respectively, showing a correlation between DLesion and the two response group. CONCLUSIONS: Our experience demonstrated feasibility of high activity therapy of 131I-mIBG in rrmHR-NBL children as two administration intensive strategy. Dosimetric approach allowed a tailored high dose treatment maximizing the benefits of radionuclide therapy for pediatric patients while maintaining a safety profile. The assesment of DLesion contributed to have a deeper understaning of metabolic treatment effects.

PET/CT in congenital hyperinsulinism: transforming patient's lives by molecular hybrid imaging.

Congenital hyperinsulinism (HI) is a life-threatening condition characterized by severe and recurrent episodes of hypoglycaemia due to defects in key genes involved in regulating insulin secretion. The delay in diagnosis and inappropriate management of HI lead to high risk of permanent hypoglycemic brain injury. The management of HI is challenging as each form of HI (focal, diffuse, and atypical) requires its own therapeutic strategy. In HI diagnostic work-up, integrated PET/CT scan is currently the first-line imaging technique allowing to differentiate between diffuse and focal form and, in the latter case, to localize the focus within the pancreas with high precision. Only in focal HI partial pancreatectomy is the treatment of choice and a curative surgical treatment means a real chance of transforming patient's lives and HI patient's future. The aim of this review is to discuss the role of PET/CT imaging in HI scenario, its technical advantages and limitations and how successful surgery is strongly dependent on accurate preoperative assessment (genetic analysis and PET/CT scan). A multidisciplinary approach in HI diagnosis and treatment inside a single team (involving different expertise) allows to manage children safely and properly, supporting their families in an organized care network.

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.

A Pediatric Case of Well-Functioning Supernumerary Kidney: Relative Renal Function Assessment Using Radionuclide Imaging.

We present an interesting image of a well-functioning supernumerary kidney evaluated with DMSA (dimercaptosuccinic acid) renal scintigraphy in a 14-year-old girl. At 2 years of age, the patient had a diagnosis of supernumerary kidney. She remained asymptomatic up to childhood age, and then a DMSA study was required to guide the following adequate surveillance strategy. DMSA study provided a clear imaging of supernumerary kidney in the left side of the abdomen showing a regular uptake and a normal function in relation to its own size.

Unusual Presentation of Relapse in Neuroblastoma: Pancreatic Metastases Detected by 123I-MIBG Scintigraphy.

Neuroblastoma is the most common extracranial solid tumor in children and accounts for 8% to 10% of all childhood cancers. The spread of metastases is both lymphatic and hematogenous. Hematogenous route occurs most commonly in bone marrow and cortical bone; pancreatic metastases are very rare, and there are few reports about this topic in medical literature. We report the case of a 14-year-old boy who suffers a third relapse of neuroblastoma: in this patient I-MIBG confirms that lesions detected by CT were due to a relapse in pancreatic tissue and influenced subsequent therapeutic management.

Role of myocardial gated SPECT scintigraphy in the clinical suspicion of ischemic cardiomyopathy: discussion of an unusual case.

The case of a 72-year-old patient affected by myasthenia gravis under pyridostigmine therapy, admitted to the hospital for the onset of oppressive thoracic pain associated with mild enzyme increase, electrocardiographic and echocardiographic disorders, is discussed. Dypiridamole/gated SPECT perfusion scintigraphy at rest evidenced reduced coronary reserve at the level of the lateral wall with apical akinesia and normokinesia of mediobasal left ventricle. On coronarography, coronary arteries were free of significant stenoses and left ventricular apical akinesia. The diagnostic approach to ischemic cardiomyopathy with the correct sequence of performed diagnostic imaging led to the presumptive identification of a rare syndrome.

Cystic fibrosis: a surgical matter?

BACKGROUND: Gastroesophageal reflux disease (GERD) is very common in patients with chronic lung diseases. We evaluated the incidence of GERD in young patients with cystic fibrosis (CF) and defined the characteristics of gastroesophageal reflux episodes analyzed by pH-multichannel intraluminal impedance (pH-MII) and esophagogastric scintigraphy. PATIENTS AND METHODS: Since 2010, 31 patients with CF underwent pH-MII. Scintigraphy and upper endoscopy were performed in positive GERD patients. Forced expiratory volume in 1 second (FEV1%) predicted was detected. RESULTS: pH-MII was positive in 17/31 (54.8%) patients (mean age: 12.4 years; range: 4-17 years). pH monitoring detected an average of 64.6 acid reflux events 4.4 episodes >5 minutes in duration. The DeMeester score was 38.5. Impedance identified a mean number of reflux episodes of 66 (65.2% acid; 32% weakly acidic; 2.8% nonacidic), 28% of which reached the proximal esophagus. Esophageal transit and gastric emptying were delayed in 6/13 (46.1%) and in 5/15 (33.3%) cases, respectively. No differences were found in lung function between positive and negative GERD patients (P=0.88). CONCLUSIONS: Pediatric patients with CF have a high incidence of GERD with acidic events. These patients should be investigated with pH-MII and scintigraphy in order to make an early diagnosis and determine the most appropriate follow-up.

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.

Congenital hyperinsulinism and glucose hypersensitivity in homozygous and heterozygous carriers of Kir6.2 (KCNJ11) mutation V290M mutation: K(ATP) channel inactivation mechanism and clinical management.

OBJECTIVE: The ATP-sensitive K(+) channel (K(ATP)) controls insulin secretion from the islet. Gain- or loss-of-function mutations in channel subunits underlie human neonatal diabetes and congenital hyperinsulinism (HI), respectively. In this study, we sought to identify the mechanistic basis of K(ATP)-induced HI in two probands and to characterize the clinical course. RESEARCH DESIGN AND METHODS: We analyzed HI in two probands and characterized the course of clinical treatment in each, as well as properties of mutant K(ATP) channels expressed in COSm6 cells using Rb efflux and patch-clamp methods. RESULTS: We identified mutation V290M in the pore-forming Kir6.2 subunit in each proband. In vitro expression in COSm6 cells supports the mutation resulting in an inactivating phenotype, which leads to significantly reduced activity in intact cells when expressed homomerically, and to a lesser extent when expressed heteromerically with wild-type subunits. In one heterozygous proband, a fluoro-DOPA scan revealed a causal focal lesion, indicating uniparental disomy with loss of heterozygosity. In a second family, the proband, homozygous for the mutation, was diagnosed with severe diazoxide-unresponsive hypersinsulinism at 2 weeks of age. The patient continues to be treated successfully with octreotide and amlodipine. The parents and a male sibling are heterozygous carriers without overt clinical HI. Interestingly, both the mother and the sibling exhibit evidence of abnormally enhanced glucose tolerance. CONCLUSIONS: V290M results in inactivating K(ATP) channels that underlie HI. Homozygous individuals may be managed medically, without pancreatectomy. Heterozygous carriers also show evidence of enhanced glucose sensitivity, consistent with incomplete loss of K(ATP) channel activity.