Analysis of image data from the EuroNet PHL-C2 trial indicates a potential reduction in injected F-18 FDG activities in children: a proposal to update the EANM Paediatric Dosage Card.

BACKGROUND: The aim of this work is to provide the currently missing evidence that may allow an update of the Paediatric Dosage Card provided by the European Association of Nuclear Medicine (EANM) for conventional PET/CT systems. METHODS: In a total of 2082 consecutive [18F]FDG-PET scans performed within the EuroNet-PHL-C2 trial, the administered [18F]FDG activity was compared to the activity recommended by the EANM Paediatric Dosage Card. None of these scans had been rejected beforehand by the reference nuclear medicine panel of the trial because of poor image quality. For detailed quality assessment, a subset of 91 [18F]FDG-PET scans, all performed in different patients at staging, was selected according to pre-defined criteria, which (a) included only patients who had received substantially lower activities than those recommended by the EANM Paediatric Dosage Card, and (b) included as wide a range of different PET systems and imaging parameters as possible to ensure that the conclusions drawn in this work are as generally valid as possible. The image quality of the subset was evaluated visually by two independent readers using a quality scoring system as well as analytically based on a volume-of-interest analysis in 244 lesions and the healthy liver. Finally, recommendations for an update of the EANM Paediatric Dosage Card were derived based on the available data. RESULTS: The activity recommended by the EANM Paediatric Dosage Card was undercut by a median of 99.4 MBq in 1960 [18F]FDG-PET scans and exceeded by a median of 15.1 MBq in 119 scans. In the subset analysis (n = 91), all image data were visually classified as clinically useful. In addition, only a very weak correlation (r = 0.06) between activity reduction and tumour-to-background ratio was found. Due to the intended heterogeneity of the dataset, the noise could not be analysed statistically sound as the high range of different imaging variables resulted in very small subsets. Finally, a suggestion for an update of the EANM Paediatric Dosage Card was developed, based on the analysis presented, resulting in a mean activity reduction by 39%. CONCLUSION: The results of this work allow for a conservative update of the EANM Paediatric Dosage Card for [18F]FDG-PET/CT scans performed with conventional PET/CT systems.

The evidence-based role of catecholaminergic PET tracers in Neuroblastoma. A systematic review and a head-to-head comparison with mIBG scintigraphy.

BACKGROUND: Molecular imaging is pivotal in staging and response assessment of children with neuroblastoma (NB). [123I]-metaiodobenzylguanidine (mIBG) is the standard imaging method; however, it is characterised by low spatial resolution, time-consuming acquisition procedures and difficult interpretation. Many PET catecholaminergic radiotracers have been proposed as a replacement for [123I]-mIBG, however they have not yet made it into clinical practice. We aimed to review the available literature comparing head-to-head [123I]-mIBG with the most common PET catecholaminergic radiopharmaceuticals. METHODS: We searched the PubMed database for studies performing a head-to-head comparison between [123I]-mIBG and PET radiopharmaceuticals including meta-hydroxyephedrine ([11C]C-HED), 18F-18F-3,4-dihydroxyphenylalanine ([18F]DOPA) [124I]mIBG and Meta-[18F]fluorobenzylguanidine ([18F]mFBG). Review articles, preclinical studies, small case series (< 5 subjects), case reports, and articles not in English were excluded. From each study, the following characteristics were extracted: bibliographic information, technical parameters, and the sensitivity of the procedure according to a patient-based analysis (PBA) and a lesion-based analysis (LBA). RESULTS: Ten studies were selected: two regarding [11C]C-HED, four [18F]DOPA, one [124I]mIBG, and three [18F]mFBG. These studies included 181 patients (range 5-46). For the PBA, the superiority of the PET method was reported in two out of ten studies (both using [18F]DOPA). For LBA, PET detected significantly more lesions than scintigraphy in seven out of ten studies. CONCLUSIONS: PET/CT using catecholaminergic tracers shows superior diagnostic performance than mIBG scintigraphy. However, it is still unknown if such superiority can influence clinical decision-making. Nonetheless, the PET examination appears promising for clinical practice as it offers faster image acquisition, less need for sedation, and a single-day examination.

EANM procedural recommendations for managing the paediatric patient in diagnostic nuclear medicine.

PURPOSE: The manuscript aims to characterize the principles of best practice in performing nuclear medicine procedures in paediatric patients. The paper describes all necessary technical skills that should be developed by the healthcare professionals to ensure the best possible care in paediatric patients, as it is particularly challenging due to psychological and physical conditions of children. METHODS: We performed a comprehensive literature review to establish the most relevant elements of nuclear medicine studies in paediatric patients. We focused the attention to the technical aspects of the study, such as patient preparation, imaging protocols, and immobilization techniques, that adhere to best practice principles. Furthermore, we considered the psychological elements of working with children, including comforting and distraction strategies. RESULTS: The extensive literature review combined with practical conclusions and recommendations presented and explained by the authors summarizes the most important principles of the care for paediatric patient in the nuclear medicine field. CONCLUSION: Nuclear medicine applied to the paediatric patient is a very special and challenging area, requiring proper education and experience in order to be performed at the highest level and with the maximum safety for the child.

Hyponatremia in childhood urinary tract infection.

Acute urinary tract infection (UTI) is the most common bacterial infection in childhood. Although hyponatremia was described in ~ 2/3 of these children, its clinical significance is still unclear. Herein, we evaluated the prevalence and clinical implications of hyponatremia in children hospitalized with a UTI. Medical records of previously healthy children hospitalized between January 2011 and December 2016 with UTI were retrospectively reviewed. Patients (median age 5.5 months) were divided into two groups according to their sodium levels: normonatremia (Na ≥ 135 mEq/L) and hyponatremia (Na < 135 mEq/L). Hyponatremia diagnosed on admission was found in 114/219 children (49%). Hyponatremic patients experienced a more severe disease manifested by a longer hospital stay (3.8 vs 3.4 days, p = 0.003), a higher prevalence of abnormal findings on renal ultrasound (10 vs 2, p = 0.01), higher C-reactive protein (CRP) levels (8.6 vs 3.4 mg/dl, p = <0.001), and a negative correlation between sodium levels and CRP (r = - 0.38, p < 0.001).Conclusion:Hyponatremia occurs frequently in children hospitalized with UTI and is associated with elevated inflammatory markers and a more severe disease course. What is Known: • Hyponatremia, one of the most common electrolyte abnormalities, occurs in approximately 1/3 of hospitalized children and in 2/3 of children with pyelonephritis. • In certain cases of various medical conditions, hyponatremia has been shown to correlate with disease severity. What is New: • Hyponatremia in hospitalized children with UTI correlates with elevated inflammatory markers and a more severe disease course.

[THE ROLE OF BONE SCINTIGRAPHY IN THE DIAGNOSIS OF CHRONIC RECURRENT MULTIFOCAL OSTEOMYELITIS IN CHILDREN].

INTRODUCTION: This case report presents a teenage girl hospitalized due to fever, left wrist pain and elevated inflammatory markers. These clinical findings, as well as a lytic lesion seen on plain radiographs and MRI in the distal left radius, led to the working diagnosis of acute osteomyelitis. Following 4 weeks of antibiotic therapy, a bone scan was conducted due to inadequate clinical response. It showed additional skeletal lesions and led to the final diagnosis of chronic recurrent multifocal osteomyelitis (CRMO). Treatment was changed to anti-inflammatory medications with a good response. This article presents key features of CRMO and emphasizes the role of skeletal scintigraphy in establishing the diagnosis.

Improved Outcome in Local Ewing Sarcoma With an Intensified Pilot Treatment Protocol SCMCIE 94.

This study evaluated the effect of an intensified pilot protocol, SCMCIE 94, on the outcome of Ewing sarcoma (EWS). The cohort included 121 patients with local or metastatic EWS treated at a tertiary pediatric medical center with the SCMCIE 94 (protocol 3, 1994 to 2011) or an earlier protocol (protocol 2, 1988 to 1994; protocol 1, 1985 to 1988). All protocols included 4 to 6 courses of chemotherapy, radiation, and surgery. Clinical data were collected retrospectively by chart review. Survival rates for protocol 3 were as follows: all patients-5-year event-free survival (EFS): 52.5%±5.6%, 10-year EFS: 49.3%±5.8%, 5-year overall survival (OS): 68.8%±5.3%, and 10-year OS: 51.1%±6.3%; patients with localized disease (any site)-5-year EFS: 63.5%±6.0% and 5-year OS: 77.2%±5.3%; patients with localized extremity disease-5-year EFS: 78.95%±8.3%, 10-year EFS: 68.6%±10.0%, 5-year OS: 90.7%±6.2%, and 10-year OS: 71.1%±11.2%. Protocol 3 was associated with an increase in 10-year EFS of 16% overall and 33% in patients with localized extremity disease compared with protocols 1+2, and a significant improvement in 5-year EFS and OS in patients with any localized disease (P=0.001). No survival benefit was found for metastatic disease. On multivariate analysis, protocol and metastatic disease were significantly independent prognostic factors. The intensified SCMCIE 94 protocol seems to increase survival in patients with localized but not metastatic EWS.

Guidelines on nuclear medicine imaging in neuroblastoma.

Nuclear medicine has a central role in the diagnosis, staging, response assessment and long-term follow-up of neuroblastoma, the most common solid extracranial tumour in children. These EANM guidelines include updated information on 123I-mIBG, the most common study in nuclear medicine for the evaluation of neuroblastoma, and on PET/CT imaging with 18F-FDG, 18F-DOPA and 68Ga-DOTA peptides. These PET/CT studies are increasingly employed in clinical practice. Indications, advantages and limitations are presented along with recommendations on study protocols, interpretation of findings and reporting results.

Validation of the mIBG skeletal SIOPEN scoring method in two independent high-risk neuroblastoma populations: the SIOPEN/HR-NBL1 and COG-A3973 trials.

BACKGROUND: Validation of the prognostic value of the SIOPEN mIBG skeletal scoring system in two independent stage 4, mIBG avid, high-risk neuroblastoma populations. RESULTS: The semi-quantitative SIOPEN score evaluates skeletal meta-iodobenzylguanidine (mIBG) uptake on a 0-6 scale in 12 anatomical regions. Evaluable mIBG scans from 216 COG-A3973 and 341 SIOPEN/HR-NBL1 trial patients were reviewed pre- and post-induction chemotherapy. The prognostic value of skeletal scores for 5-year event free survival (5 yr.-EFS) was tested in the source and validation cohorts. At diagnosis, both cohorts showed a gradual non-linear increase in risk with cumulative scores. Several approaches were explored to test the relationship between score and EFS. Ultimately, a cutoff score of ≤3 was the most useful predictor across trials. A SIOPEN score ≤ 3 pre-induction was found in 15% SIOPEN patients and in 22% of COG patients and increased post-induction to 60% in SIOPEN patients and to 73% in COG patients. Baseline 5 yr.-EFS rates in the SIOPEN/HR-NBL1 cohort for scores ≤3 were 47% ± 7% versus 26% ± 3% for higher scores at diagnosis (p < 0.007) and 36% ± 4% versus 14% ± 4% (p < 0.001) for scores obtained post-induction. The COG-A3973 showed 5 yr.-EFS rates for scores ≤3 of 51% ± 7% versus 34% ± 4% for higher scores (p < 0.001) at diagnosis and 43% ± 5% versus 16% ± 6% (p = 0.004) for post-induction scores. Hazard ratios (HR) significantly favoured patients with scores ≤3 after adjustment for age and MYCN-amplification. Optimal outcomes were recorded in patients who achieved complete skeletal response. CONCLUSIONS: Validation in two independent cohorts confirms the prognostic value of the SIOPEN skeletal score. In particular, patients with an absolute SIOPEN score > 3 after induction have very poor outcomes and should be considered for alternative therapeutic strategies.

Re-evaluation of bone pain in patients with type 1 Gaucher disease suggests that bone crises occur in small bones as well as long bones.

Bone crises in type 1 Gaucher disease are reported in long bones and occasionally in weight bearing bones and other bones, but rarely in small bones of the hands and feet. We retrospectively examined the incidence of bone pain in patients followed at the Rabin Medical Center, Israel, before and following the initiation of enzyme replacement therapy (ERT) and evaluated them for bone crises. Of 100 type I Gaucher disease patients, 30 (30%) experienced one or more bone crises. Small bone crises represented 31.5% of all bone crises and were always preceded by crises in other bones. While the incidence of long bone crises reduced after the initiation of ERT, small bone crises increased. Almost 60% of patients with bone crises were of the N370S/84GG genotype suggesting a greater susceptibility of N370S/84GG patients to severe bone complications. These patients also underwent the greatest number of splenectomies (70.6% of splenectomised patients). Splenectomised patients showed a trend towards increased long and small bone crises after surgery. Active investigation of acute pain in the hands and feet in patients in our cohort has revealed a high incidence of small bone crises. Physicians should consider imaging studies to investigate unexplained pain in these areas.

Prenatal sonographic predictors of postnatal pyeloplasty in fetuses with isolated hydronephrosis.

OBJECTIVE: To define prenatal sonographic predictors of ureteropelvic junction obstruction requiring postnatal pyeloplasty, in fetuses with isolated hydronephrosis. METHODS: Retrospective data on prenatal sonographic parameters were compared between patients who had been diagnosed prenatally with hydronephrosis and either underwent postnatal pyeloplasty for ureteropelvic junction obstruction (n = 39) or were treated conservatively (n = 30). RESULTS: Significant differences between the surgically and conservatively treated patients were found for mean anterior-posterior renal diameter (22.8 ± 8.6 vs 14.2 ± 5.9 mm, respectively, p < 0.0001) and parenchymal thickness (5.9 ± 2.8 vs 8.1 ± 2.6 mm, p = 0.009). Anterior-posterior diameter >14 mm was the best single predictor of the need for surgery (area under the ROC curve, 0.817), with sensitivity 77%, specificity 69%, positive predictive value (PPV) 77% and negative predictive value (NPV) 69% (ß = 1.17, 95%CI = 1.07-1.28, p < 0.001). Mean ratio of anterior-posterior diameter to parenchymal thickness was significantly higher in the postnatal pyeloplasty group (5.4 ± 4.5 vs 2.1 ± 1.4, p = 0.0001). A ratio >2.1 had a sensitivity of 87% and specificity of 65% for the need for surgery (area under the curve 0.822, PPV 79%, NPV 77%; ß = 1.92, 95%CI = 1.16-3.17, p < 0.001). CONCLUSION: In cases of prenatal isolated hydronephrosis, the pelvic anterior-posterior diameter and parenchymal thickness may predict the need for postnatal pyeloplasty. A ratio of >2.1 of pelvic anterior-posterior diameter to parenchymal thickness suggests ureteropelvic junction obstruction and supports the use of more intensive prenatal and postnatal surveillance.

Beyond current guidelines: reduction in minimum administered radiopharmaceutical activity with preserved diagnostic image quality in pediatric hepatobiliary scintigraphy.

PURPOSE: To determine if the minimum administered radiopharmaceutical activity for hepatobiliary scintigraphy can be reduced while preserving diagnostic image quality using enhanced planar processing (EPP). METHODS: A total of 40 infants between 10 and 270 days old (body mass 2.2 - 6.5 kg) had hepatobiliary scintigraphy during the period 2004 - 2010 following the intravenous administration of either (99m)Tc-mebrofenin (18 patients) or (99m)Tc-disofenin (22 patients). Due to the small size of these patients, they all received the minimum administered activity of 18.5 MBq consistent with the North American Consensus Guidelines. Six nuclear medicine physicians subjectively graded the acceptability of the image quality for clinical interpretation using a four-point scale (not acceptable, fair, good, excellent). Each physician independently graded seven image sets including the original study (full activity) and simulated reduced activity studies using binomial subsampling (50% of full activity, 25% of full activity and activity reduced by weight), with and without EPP. RESULTS: For full-activity studies, 98% were deemed acceptable by the six physicians for clinical interpretation. The percentages of acceptable 50% reduced activity studies with and without EPP were not significantly different from the percentage of acceptable full-activity studies (P = 0.193 and P = 0.998, respectively). The percentage of acceptable 25% reduced activity studies without EPP was significantly different from the percentage of acceptable full-activity studies (P < 0.001); however, this difference vanished when EPP was applied (P = 0.482). The activity reduced by weight ranged from 1.85 to 4.81 MBq (10% to 26% of full dose) and the percentages of acceptable studies with and without EPP were significantly different from the percentage of acceptable full-activity studies (P < 0.001 and P = 0.02, respectively). CONCLUSION: Clinically interpretable hepatobiliary scintigraphy images can be obtained in infants when the minimum administered activity is substantially reduced. Without EPP, clinically acceptable images may be produced with a reduction of 50%, and with EPP, a reduction of 75% or more may be possible.

[Guidelines for wise utilization of knee imaging].

BACKGROUND: The knee is a complex structure afflicted with diverse pathologies. Correct management of knee complaints demands wise utilization of imaging modalities, considering their accuracy in the specific clinical situation, the patient's safety and availability and financial issues. Some of these considerations are universal, while others are local, depending on medical and insurance systems. There is controversy and unclearness regarding the best imaging modality in different clinical situations. PURPOSE: To develop clinical guidelines for utilizing knee imaging. METHODS: Leading physicians in specialties associated with knee disease and imaging were invited to participate in a panel on the guidelines. Controversies were settled in the main panel or in sub-panels. RESULTS: The panel agreed on the principles in choosing from the various modalities, primarily medical accuracy, followed by patient safety, availability and cost. There was agreement that the physician is responsible to choose the most appropriate diagnostic tool, consulting, when necessary, on the advantages, limitations and risks of the various imaging modalities. A comprehensive table was compiled with the importance of the different imaging modalities in various clinical situations. DISCUSSION AND SUMMARY: For the first time, Israeli guidelines on wise utilization of knee imaging are presented. They take into consideration the clinical situations and also availability and financial issues specific to Israel. These guidelines will serve physicians of several disciplines and medical insurers to improve patient management efficiently.

Pediatric Nephro-Urology: Overview and Updates in Diuretic Renal Scans and Renal Cortical Scintigraphy.

Nuclear medicine offers several diagnostic scans for the evaluation of congenital and acquired conditions of the kidneys and urinary track in children. Tc-99m-MAG 3 diuretic renal scans are most commonly used in the evaluation and follow up of urinary track dilatations. They provide functional information on the differential renal function and on drainage quality which is allows distinction between obstructed and non-obstructed kidneys and the need for surgical correction vs conservative management in kidneys with impaired drainage. Standardized imaging and processing protocols are essential for correct interpretation and for meaningful comparisons between follow up scans. Different approaches and conceptions led to some contradicting recommendations between SNMMI and EANM guidelines on diuretic renography in children which caused confusion and to the emergence of self-made institutional protocols. In Late 2018 the two societies published joint procedural guidelines on diuretic renography in infants and children which hopefully will end the confusion. Tc-99m DMSA scans provide important information about the function of the renal cortex allowing detection of acute pyelonephritis, renal scars dysplasia and ectopy as well as accurate determination of the differential renal function. They are commonly used in the evaluation of children with urinary tract infections and affect clinical management. A standardized imaging and processing protocol improves the diagnostic accuracy of these studies. SPECT or pinhole images should be a routine part of the imaging protocol. This is one of the recommendations in the new EANM and SNMMI procedural guidelines for renal cortical scintigraphy in children available online on the SNMMI website and is under publication. This article provides an overview on the clinical role of diuretic renography and cortical scintigraphy in children and describes the imaging protocols focusing on the new recommendations in the procedural guidelines.

SNMMI Procedure Standard/EANM Practice Guideline on Pediatric 18F-FDG PET/CT for Oncology 1.0.

PREAMBLEThe Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional nonprofit medical association founded in 1985 to facilitate communication worldwide among individuals pursuing clinical and academic excellence in nuclear medicine. SNMMI and EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine.The SNMMI and EANM will periodically put forth new standards/guidelines for nuclear medicine practice to help advance the science of nuclear medicine and improve service to patients. Existing standards/guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each standard/guideline, representing a policy statement by the SNMMI/EANM, has undergone a thorough consensus process, entailing extensive review. The SNMMI and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging requires particular training and skills, as described in each document. These standards/guidelines are educational tools designed to assist practitioners in providing appropriate and effective nuclear medicine care for patients. These guidelines are consensus documents, and are not inflexible rules or requirements of practice. They are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, the SNMMI and the EANM cautions against the use of these standards/guidelines in litigation in which the clinical decisions of a practitioner are called into question.The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that action differing from what is laid out in the standards/guidelines, standing alone, is below standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the standards/guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the standards/guidelines.The practice of medicine involves not only the science, but also the art of dealing with the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible for general guidelines to consistently allow for an accurate diagnosis to be reached or a particular treatment response to be predicted. Therefore, it should be recognized that adherence to these standards/guidelines will not ensure a successful outcome. All that should be expected is that the practitioner follows a reasonable course of action, based on their level of training, the current knowledge, the available resources, and the needs/context of the particular patient being treated.PET and computerized tomography (CT) have been widely used in oncology. 18F-FDG is the most common radiotracer used for PET imaging. The purpose of this document is to provide imaging specialists and clinicians guidelines for recommending, performing, and interpreting 18F-FDG PET/CT in pediatric patients in oncology. There is not a high level of evidence for all recommendations suggested in this paper. These recommendations represent the expert opinions of experienced leaders in this field. Further studies are needed to have evidence-based recommendations for the application of 18F-FDG PET/CT in pediatric oncology. These recommendations should be viewed in the context of good practice of nuclear medicine and are not intended to be a substitute for national and international legal or regulatory provisions.

Detecting lumbar lesions in 99m Tc-MDP SPECT by deep learning: Comparison with physicians.

PURPOSE: 99m Tc-MDP single-photon emission computed tomography (SPECT) is an established tool for diagnosing lumbar stress, a common cause of low back pain (LBP) in pediatric patients. However, detection of small stress lesions is complicated by the low quality of SPECT, leading to significant interreader variability. The study objectives were to develop an approach based on a deep convolutional neural network (CNN) for detecting lumbar lesions in 99m Tc-MDP scans and to compare its performance to that of physicians in a localization receiver operating characteristic (LROC) study. METHODS: Sixty-five lesion-absent (LA) 99m Tc-MDP studies performed in pediatric patients for evaluating LBP were retrospectively identified. Projections for an artificial focal lesion were acquired separately by imaging a 99m Tc capillary tube at multiple distances from the collimator. An approach was developed to automatically insert lesions into LA scans to obtain realistic lesion-present (LP) 99m Tc-MDP images while ensuring knowledge of the ground truth. A deep CNN was trained using 2.5D views extracted in LP and LA 99m Tc-MDP image sets. During testing, the CNN was applied in a sliding-window fashion to compute a 3D "heatmap" reporting the probability of a lesion being present at each lumbar location. The algorithm was evaluated using cross-validation on a 99m Tc-MDP test dataset which was also studied by five physicians in a LROC study. LP images in the test set were obtained by incorporating lesions at sites selected by a physician based on clinical likelihood of injury in this population. RESULTS: The deep learning (DL) system slightly outperformed human observers, achieving an area under the LROC curve (AUCLROC ) of 0.830 (95% confidence interval [CI]: [0.758, 0.924]) compared with 0.785 (95% CI: [0.738, 0.830]) for physicians. The AUCLROC for the DL system was higher than that of two readers (difference in AUCLROC [ΔAUCLROC ] = 0.049 and 0.053) who participated to the study and slightly lower than that of two other readers (ΔAUCLROC  = -0.006 and -0.012). Another reader outperformed DL by a more substantial margin (ΔAUCLROC  = -0.053). CONCLUSION: The DL system provides comparable or superior performance than physicians in localizing small 99m Tc-MDP positive lumbar lesions.

Asplenia and functional hyposplenism in autoimmune polyglandular syndrome type 1.

Asplenia was diagnosed in four patients with autoimmune polyendocrine syndrome type-I (APS-I): two children, aged 2-4 years, from the same family and two adults, the father of the two children and his cousin. We have observed a worsening in splenic function in the children during a follow-up of a few years. Patients with APS-I should be evaluated for splenic function, since splenic dysfunction has important therapeutic implications, especially in children.

SCMCIE94: an intensified pilot treatment protocol known to be associated with cure in CD 56-negative non-pelvic isolated Ewing sarcoma (EWS) is also associated with no early relapses in non-metastatic extremity EWS.

PURPOSE: We report the unexpected absence of early relapse (before 30 months) in 24 consecutive patients with isolated limb primary Ewing sarcoma treated with an intensified pilot protocol, SCMCIE94. METHODS: Clinical data for the study were collected retrospectively from the patient files. The protocol included 6 courses of chemotherapy, split radiation, and limb salvage surgery. This SCMCIE94 protocol had been used in almost all the patients described in an earlier report, in whom those with non-pelvic isolated tumors and low/absent CD56 expression in Ewing sarcoma tumor cells were all long-term survivors. RESULTS: The 5-year (10-year) event-free survival rate for the patients with isolated limb primary Ewing sarcoma was 78.95 ± 8.3% (68.6 ± 10.0%) and the overall survival rate was 90.7 ± 6.2% (71.1 ± 11.2%). There were no relapses before 30 months in any of these patients. CONCLUSION: The intensified SCMCIE94 pilot protocol has been shown previously to cure patients with localized CD56-negative non-pelvic Ewing sarcoma. The present study shows that among all patients with localized extremity disease who were treated with this protocol, there were no cases of early relapse. Although our cohort was small, the difference in results from studies using other protocols is so striking, that it would seem reasonable to assume it is attributable to the changes made in the protocol itself rather than risk factors. Late relapses of isolated limb CD56-positive Ewing sarcoma suggest minimal residual disease warranting additional therapeutic approaches such as autologous stem cell rescue after Busulfan Melfelan.

[Acne--merely a cosmetic problem? Acne associated musculoskeletal syndromes].

Acne can be associated with severe musculoskeletal and constitutional symptoms. This is a case history of a 15 year-old boy with severe acne, treated with isotretinoin, who was admitted because of high fever and weight loss of 3 weeks duration. His complaints were of severe chest and back pain, and inability to walk. His laboratory results revealed elevated erythrocyte sedimentation rate and C-reactive protein. On a pelvic radiograph bilateral sacroiliitis was noticed. Radionuclide bone scan revealed increased uptake in the right sacroiliac joint, in small vertebral bodies and sternum. A diagnosis of acne-associated musculoskeletal syndrome was made and the patient was treated with high dose steroids. His symptoms resolved and his acne improved. This case report sheds light on the relationship between acne and associated musculoskeletal syndromes. Physicians should be aware of this association in order to provide prompt and efficient treatment.