Paolo Tomà

Bronchioloalveolar carcinoma arising in congenital cystic adenomatoid malformation in a child: A case report and review on malignancies originating in congenital cystic adenomatoid malformation

A type I congenital cystic adenomatoid malformation (CCAM) in the left lower lobe was removed from a 11‐year‐old boy with a 3‐month history of recurrent pneumonia. As incidental finding, a bronchioloalveolar carcinoma (BAC) was found in the lung parenchyma adjacent to the cyst. A left lower lobectomy was performed. At 18 months after surgery the patient is well and free of neoplastic disease. To the best of our knowledge, this association has not been reported previously in a pediatric patient. Malignancies complicating CCAM are rarely seen, but have been reported in adults. Including our case, eight cases of BAC and five cases of rhabdomyosarcoma (RMS) in association with CCAM have been reported so far. As CCAM can host metaplastic mucous cells, primitive mesenchymal cells and differentiated but poorly organized striated muscle fibers, it has been proposed that CCAM may act as a predisposing condition for oncogenesis. Our experience adds further support that CCAM can act as a premalignant lesion. Previous reports of both BAC and RMS in asymptomatic CCAM suggest prompt resection shortly after diagnosis. Pediatr. Pulmonol. 1998; 25:62–66.

A Prospective Study on the Epidemiology of Febrile Episodes during Chemotherapy-Induced Neutropenia in Children with Cancer or after Hemopoietic Stem Cell Transplantation

BACKGROUND The purpose of our study was to evaluate the incidence and clinical characteristics of febrile episodes during neutropenia following chemotherapy in children with cancer. PATIENTS AND METHODS A prospective, 3-year single-center observational study of periods of neutropenia was performed. Epidemiology and clinical diagnoses of febrile episodes occurring during the neutropenic periods were evaluated, taking into consideration different categories of anticancer treatment based on the type of tumor and phase of therapy. RESULTS A total of 703 febrile episodes were observed during 614 (34%) of 1792 neutropenic periods (34%), for a total of 28,001 days at risk, accounting for a rate of 0.76 episodes per 30 days at risk. The highest proportions of neutropenic periods with primary febrile episodes were observed after autologous hemopoietic stem cell transplantation (58%), aggressive treatment for acute leukemia or non-Hodgkin lymphoma (48%), and allogeneic hemopoietic stem cell transplantation (44%); the lowest proportion (9%) was observed during maintenance chemotherapy for acute leukemia (P<.001). The most frequent clinical diagnosis was fever of unknown origin (in 79% of cases), followed by bacteremia (10%); invasive mycosis was diagnosed in only 2% of cases. CONCLUSIONS The overall incidence of febrile neutropenia and severe infectious complications in children with cancer is low, with differences according to the aggressiveness of chemotherapy. This fact must be considered when designing clinical trials on the management of infectious complications in children with cancer.

Treatment of EBV-Related Post-Renal Transplant Lymphoproliferative Disease with a Tailored Regimen Including EBV-Specific T Cells

The treatment of EBV‐associated post‐transplant lymphoproliferative disease (PTLD) poses a considerable challenge. Efforts have been made to define regimens based on combination of the available therapeutic agents, chosen and tailored on a patient‐by‐patient basis, with the aim of augmenting event‐free patient and graft survival. Recently, autologous EBV‐specific cytotoxic T‐lymphocytes (CTL) have proved effective in enhancing EBV‐specific immune responses and reducing viral load in organ transplant recipients with active infection. We investigated the use of a tailored combined approach including autologous EBV‐specific CTL for the treatment of EBV‐related PTLD developing after pediatric kidney transplantation.

Synovial and inflammatory diseases in childhood: role of new imaging modalities in the assessment of patients with juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) represents a group of heterogeneous diseases characterized by a chronic inflammatory process primarily targeting the synovial membrane. A persistent synovitis is associated with an increased risk of osteocartilaginous damage.With the advent of effective structure-modifying treatment for JIA, it may be possible to significantly reduce or even completely prevent structural damage and associated functional disability. The trend towards early suppression of inflammation, in order to prevent erosive disease, shifts the emphasis away from conventional radiographic detectable structural damage to the slightest traces of early joint damage, and drives the need for alternative imaging techniques more sensitive in detecting early signs of disease activity and damage. In this regard MRI and US are playing an increasing role in the evaluation of arthritic joints.This article will review the key aspects of the current status and recent important advances of imaging techniques available to investigate the child with rheumatic disease, briefly discussing conventional radiography, and particularly focusing on MRI and US. In this era of advancing imaging technology, knowledge of the relative values of available imaging techniques is necessary to optimize the management of children with JIA.

Localized resectable neuroblastoma: results of the second study of the Italian Cooperative Group for Neuroblastoma.

PURPOSE To optimize treatment for children with localized resectable neuroblastoma in 21 Italian institutions using a common protocol based on previous experience. PATIENTS AND METHODS Between January 1985 and December 1992, 152 children aged 0 to 15 years with nondisseminated neuroblastoma were entered onto this study following complete resection of tumor without tumor rupture (TR) (stage 1), or resection with minimal tumor residue, and/or tumor infiltration of regional lymph nodes (LN+), and/or TR (stage 2). Of 144 assessable children, 69 were classified as having stage 1 disease and 75 as stage 2. Of stage 2 children, 49 had low-risk (LR) characteristics (age, 0 to 11 months or 1 to 15 years but negative lymph nodes and no TR). Stage 1 and stage 2 LR children did not receive adjuvant therapy. The remaining 26 stage 2 children had high-risk (HR) characteristics (age, 1 to 15 years with LN+ and/or TR) and received adjuvant chemotherapy for 6 months. RESULTS Of 144 children, three died of therapy-related complications and 19 relapsed, of whom six died of disease. The estimated 5-year overall survival (OS) rate was 93% and the event-free survival (EFS) rate was 83%. Of 69 stage 1 children, one died postoperatively and five relapsed (one local and four disseminated, two of whom died), for 94% OS and 90% EFS rates. Of 49 stage 2 LR children, six relapsed (four local and two disseminated); relapses occurred in five of 20 infants with LN+, in one of four infants with TR, and in none of the remaining 25 children. One child died of disease and one of toxicity, for 96% OS and 85% EFS rates. Of 26 stage 2 HR children, eight relapsed (three of 20 with LN+, three of four with TR, and two of two with LN+ and TR), of whom three died of disease and one of toxicity, for 87% OS and 61% EFS rates. CONCLUSION Our data confirm the overall good prognosis of children with localized resectable neuroblastoma. LN+ and TR predisposed to relapse at all ages, but infants tended to have a less aggressive course after relapse. Stage 1 and 2 LR children had 94% and 96% OS rates, respectively, which justifies a policy of no adjuvant chemotherapy. Eight of 26 children with stage 2 HR relapsed despite 6 months of chemotherapy; for these children, more intensive chemotherapy may be required.

Dynamic contrast-enhanced magnetic resonance imaging in the assessment of disease activity in patients with juvenile idiopathic arthritis

OBJECTIVE To determine the capability and reliability of dynamic contrast-enhanced MRI (DCE-MRI) in the assessment of disease activity in juvenile idiopathic arthritis (JIA). METHODS DCE-MRI of the clinically more affected wrist or hip joints was undertaken in 21 patients, coupled with standard clinical assessment and biochemical analysis. Synovial inflammation was assessed by computing the maximum level of synovial enhancement (ME), the maximum rate of enhancement (MV) and the rate of early enhancement (REE) from the enhancement curves generated from region of interest independently delineated by two readers in the area of the ME. Correlations between dynamic parameters and clinical measures of disease activity, and static MRI synovitis score were investigated. RESULTS In patients with wrist arthritis, REE correlated with the wrist swelling score (r(s) = 0.72), ESR (r(s) = 0.69), pain assessment scale (r(s) = 0.63) and childhood HAQ (r(s) = 0.60). In patients with hip arthritis, ME correlated with the hip limitation of motion (r(s) = 0.69). Static MRI synovitis score based on post-gadolinium enhancement correlated with MV (r(s) = 0.63) in patients with wrist arthritis and with ME (r = 0.68) in those with hip arthritis. The inter-reader agreement assessed by intra-class correlation coefficient (ICC) for ME, MV and REE (ICC = 0.98, 0.97 and 0.84, respectively) was excellent. CONCLUSIONS DCE-MRI represents a promising method for the assessment of disease activity in JIA, especially in patients with wrist arthritis. As far as we know, this study is the first to demonstrate the feasibility, reliability and construct validity of DCE-MRI in JIA. These results should be confirmed in large-scale longitudinal studies in view of its further application in therapeutic decision making and in clinical trials.

Development and preliminary validation of a paediatric-targeted MRI scoring system for the assessment of disease activity and damage in juvenile idiopathic arthritis

Objectives To develop and validate a paediatric-targeted MRI scoring system for the assessment of disease activity and damage in juvenile idiopathic arthritis (JIA). To compare the paediatric MRI score with the adult-designed. Outcome Measures in Rheumatology Clinical Trials—Rheumatoid Arthritis MRI Score (RAMRIS), whose suitability for assessing growing joints was tested. Methods In 66 patients with JIA the clinically more affected wrist was studied. Thirty-nine patients had a 1-year MRI follow-up. Two readers independently assigned the paediatric score and the RAMRIS to all studies. Validation procedures included analysis of reliability, construct validity and responsiveness to change. A reduced version of the bone erosion score was also developed and tested. Results The paediatric score showed an excellent reproducibility (interclass correlation coefficient >0.9). The interobserver agreement of RAMRIS was moderate for bone erosions and excellent for bone marrow oedema (BMO). The paediatric score and RAMRIS provided similar results for construct validity. The responsiveness to change of the paediatric score was moderate for synovitis and bone erosion, and poor for BMO and did not improve when RAMRIS was applied. The reduced version of the bone erosion was valuable for the assessment of joint damage, and provided time-saving advantages. Conclusion The results demonstrate that the paediatric MRI score is a reliable and valid method for assessing disease activity and damage in JIA. Unexpectedly, the RAMRIS provides acceptable suitability for use in the paediatric age group. Further work, especially in a longitudinal setting, is required before defining the most suitable MRI scale for assessing growing joints.

Performance of the galactomannan antigen detection test in the diagnosis of invasive aspergillosis in children with cancer or undergoing haemopoietic stem cell transplantation

Serum galactomannan (GM) antigen detection is not recommended for defining invasive aspergillosis (IA) in children undergoing aggressive chemotherapy or allogeneic haemopoietic stem cell transplantation (HSCT). The ability of the GM test to identify IA in children was retrospectively evaluated in a cohort of children. Test performance was evaluated on samples that were collected during 195 periods at risk of IA. Proven IA was diagnosed in seven periods, all with positive GM test results (true positives, 4%), and possible IA was diagnosed in 15 periods, all with negative GM test results (false negatives, 8%). The test result was positive with negative microbiological, histological and clinical features in three periods (false positives, 1%), and in 170 periods it was negative with negative microbiological, histological and clinical features (true negatives, 87%). The sensitivity was 0.32 and the specificity was 0.98; the positive predictive value was 0.70 and the negative predictive value was 0.92. The efficiency of the test was 0.91, the positive likelihood ratio was 18.3, and the negative likelihood ratio was 1.4. The probability of missing an IA because of a negative test result was 0.03. Test performance proved to be better during at-risk periods following chemotherapy than in periods following allogeneic HSCT. The GM assay is useful for identifying periods of IA in children undergoing aggressive chemotherapy or allogeneic HSCT.

Hennekam syndrome presenting as nonimmune hydrops fetalis, congenital chylothorax, and congenital pulmonary lymphangiectasia

We report a female infant with congenital lymphedema, facial anomalies, intestinal lymphangiectasia consistent with a diagnosis of Hennekam syndrome. At birth the patient presented with severe respiratory distress due to nonimmune hydrops fetalis, a congenital chylothorax (CC), and pulmonary lymphangiectasia. Hydrops fetalis may be present in newborns with the Hennekam syndrome. Lymphoscintigraphy can be useful in explaining pleural‐pulmonary involvement of this generalized lymph vessel malformation syndrome.

CT and MRI of paediatric Crohn disease.

Over the past two decades there has been considerable evolution in cross-sectional imaging modalities for the evaluation of Crohn disease (CD) in children. CT and MRI have contributed to conventional techniques so that now radiology has an even greater role in the management of CD, monitoring disease progression and detecting complications. The role of CT and MRI, their limitations, and the various imaging features that the radiologist should be aware of are discussed in this review.