Mervyn D. Cohen

Imatinib mesylate for plexiform neurofibromas in patients with neurofibromatosis type 1: a phase 2 trial

BACKGROUND Plexiform neurofibromas are slow-growing chemoradiotherapy-resistant tumours arising in patients with neurofibromatosis type 1 (NF1). Currently, there are no viable therapeutic options for patients with plexiform neurofibromas that cannot be surgically removed because of their proximity to vital body structures. We undertook an open-label phase 2 trial to test whether treatment with imatinib mesylate can decrease the volume burden of clinically significant plexiform neurofibromas in patients with NF1. METHODS Eligible patients had to be aged 3-65 years, and to have NF1 and a clinically significant plexiform neurofibroma. Patients were treated with daily oral imatinib mesylate at 220 mg/m(2) twice a day for children and 400 mg twice a day for adults for 6 months. The primary endpoint was a 20% or more reduction in plexiform size by sequential volumetric MRI imaging. Clinical data were analysed on an intention-to-treat basis; a secondary analysis was also done for those patients able to take imatinib mesylate for 6 months. This trial is registered with ClinicalTrials.gov, number NCT01673009. FINDINGS Six of 36 patients (17%, 95% CI 6-33), enrolled on an intention-to-treat basis, had an objective response to imatinib mesylate, with a 20% or more decrease in tumour volume. Of the 23 patients who received imatinib mesylate for at least 6 months, six (26%, 95% CI 10-48) had a 20% or more decrease in volume of one or more plexiform tumours. The most common adverse events were skin rash (five patients) and oedema with weight gain (six). More serious adverse events included reversible grade 3 neutropenia (two), grade 4 hyperglycaemia (one), and grade 4 increases in aminotransferase concentrations (one). INTERPRETATION Imatinib mesylate could be used to treat plexiform neurofibromas in patients with NF1. A multi-institutional clinical trial is warranted to confirm these results. FUNDING Novartis Pharmaceuticals, the Indiana University Simon Cancer Centre, and the Indiana University Herman B Wells Center for Pediatric Research.

CT with a Computer-Simulated Dose Reduction Technique for Detection of Pediatric Nephroureterolithiasis: Comparison of Standard and Reduced Radiation Doses

OBJECTIVE The purpose of this study was to compare the diagnostic capabilities of standard- and reduced-dose CT in the detection of nephroureterolithiasis in children. MATERIALS AND METHODS Forty-five patients 20 years old or younger divided into two groups weighing 50 kg or less and more than 50 kg underwent unenhanced 16-MDCT in the evaluation of acute flank pain. An investigational computer-simulated tube current reduction tool was used to produce additional 80- and 40-mA examination sets (total number of image sets=135). Three independent blinded readers ranked random images for stones (confidence scale, 1-5, least to most), hydronephrosis, noise-based image quality, and presence of nonrenal lesions. RESULTS Compared with the standard tube current used for the original CT scans, there was no significant reduction (p=0.37) in detection of renal stones at the 80-mA setting (mean dose reduction, 67%; range, 43-81%); and at the 40-mA setting (mean dose reduction, 82%; range, 72-90%), the detection rate was significantly lower (p=0.05). At the 40-mA setting, there was no significant difference among the children weighing 50 kg or less (p=0.4). Detection of ureteral stones and hydronephrosis was not significantly different at 80 and 40 mA; however, disease frequency was low, and no definite conclusion can be made. CONCLUSION Simulated dose reduction is a useful tool for determining diagnostic thresholds for MDCT detection of renal stones in children. Use of the 80-mA setting for all children and 40 mA for children weighing 50 kg or less does not significantly affect the diagnosis of pediatric renal stones.

Imaging of Children with Cancer

Provides detailed descriptions of tumours in children, encompassing pathology, clinical presentation, imaging studies, differential diagnoses and treatment. Each chapter describes the tumours of a specific body system. Central nervous system (CNS) tumours are also discussed.

The Fontan Procedure: Anatomy, Complications, and Manifestations of Failure

The Fontan procedure refers to any operation that results in the flow of systemic venous blood to the lungs without passing through a ventricle. It is performed to treat several complex congenital heart abnormalities including tricuspid atresia, pulmonary atresia with intact ventricular septum, hypoplastic left heart syndrome, and double-inlet ventricle. The original Fontan procedure included direct anastomosis of the right atrium to the main pulmonary artery; however, multiple modifications have been employed. Creation of Fontan circulation is palliative in nature, with good results in patients with ideal hemodynamics and substantial morbidity and mortality in those with poor hemodynamics. Complications of Fontan circulation include exercise intolerance, ventricular failure, right atrium dilatation and arrhythmia, systemic and hepatic venous hypertension, portal hypertension, coagulopathy, pulmonary arteriovenous malformation, venovenous shunts, and lymphatic dysfunction (eg, ascites, edema, effusion, protein-losing enteropathy, and plastic bronchitis). Magnetic resonance imaging is best for postoperative evaluation of patients who underwent the Fontan procedure, and cardiac transplantation remains the only definitive treatment for those with failing Fontan circulation.

Gastric tube placement in young children.

In this study, the internal position of a nasogastric/orogastric tube was determined in 72 children, prior to an abdominal radiograph, by measuring CO2 and pH and bilirubin of tube aspirate. Fifteen of the 72 tubes (20.8%) were incorrectly placed on radiograph. Using the suggested adult cutoff of pH 5, pH of aspirate correctly predicted misplacement outside the stomach in 7/28 (25%) of children and correctly predicted correct placement in the stomach in 34 of 40 children (85%). Using the suggested adult cutoff of bilirubin ≥ 5 mg/dL, bilirubin monitoring failed to identify either of two incorrectly placed tubes. In this study, using an algorithm of assuming stomach placement if the pH of aspirate is ≤ 5 and obtaining an abdominal radiograph when either no aspirate is obtained or the pH is >5 would have resulted in 92% accuracy. Alternatively, obtaining an abdominal radiograph would result in nearly 100% accuracy.

The Detection of Pulmonary Metastases by Helical Ct: A Clinicopathologic Study in Dogs

PURPOSE We sought to determine the accuracy of helical CT in the detection of pulmonary metastases. METHOD Four anesthetized dogs with metastatic osteosarcoma underwent helical CT with a collimation of 5 mm, a pitch of 2, and a reconstruction interval of 5 mm. All macroscopically evident metastases were recorded at autopsy. CT images were independently reviewed by 10 radiologists and compared with pathologic results. Alternate slices in the dog with the most metastases were microscopically examined in their entirety. RESULTS Pathologic examination of the lungs revealed 132 macroscopically evident pulmonary metastases, of which 74 (56%) were detected by at least one reader. Forty-four of the 99 (44%) metastases of < or = 5 mm in diameter were detected by at least one reader compared with 30 of 33 (91%) metastases of > 5 mm in diameter (p < 0.0001). The 10 readers reported a total of 107 false positives. Complete microscopy of alternate slices in the dog with the most metastases (n = 68) revealed an additional 38 micrometastases of < or = 3 mm in diameter. None of the 32 micrometastases of < or = 1 mm were detected by CT. CONCLUSION Helical CT has some limitations in the detection of pulmonary metastases.

Improving clinical histories on radiology requisitions

PURPOSE The Health Care Financing Administration (HCFA) regards billing for radiologic examinations without an appropriate indication as unlawful, and both the referring physician and the radiologist are liable. HCFA regulations are interpreted as requiring that all requisitions for radiologic examinations include a current diagnosis and appropriate indication for the study. The purpose of this investigation was to determine the rates at which requisitions currently meet these criteria and to assess the effectiveness of a simple intervention designed to improve them. MATERIALS AND METHODS One hundred fifty consecutive chest radiography requisitions were examined to determine the rate at which current diagnoses and appropriate indications were present. An intervention was then implemented that included a month-long effort to inform referring physicians and radiologists of HCFA regulations, followed by a 1-week period during which requested examinations were not performed unless accompanied by a clinical diagnosis and appropriate indication. Another 150 consecutive chest radiography requisitions were then assessed to determine the effect of the intervention. A 3-month follow-up sample of a third set of 150 consecutive requisitions was then obtained. RESULTS The intervention produced a 69% decrease in the rate at which current diagnoses were missing from requisitions, and a 61% decrease in the corresponding rate for appropriate indications. Both results are significant with chi2 analysis at the P = .001 level. After 3 months with no additional intervention, rates decayed back toward baseline, with only a 35% remaining decrease for current diagnosis and an 18% decrease for appropriate indication. CONCLUSION The intervention performed in this study significantly reduces the rate of noncompliance with HCFA regulations. However, this improvement decays over time if it is not reinforced.

Magnetic Resonance Differentiation of Acute and Chronic Osteomyelitis in Children

A comparison has been made of the MRI findings of 17 studies in 16 patients with osteomyelitis: eight studies were performed in patients with acute osteomyelitis, six in chronic and three in healed osteomyelitis. Soft tissues, cortex and marrow were assessed in all patients. The best predictors of acute osteomyelitis were poorly defined soft tissue planes, absence of cortical thickening, and a poor interface between normal and diseased marrow. In contrast, chronic osteomyelitis was suggested by the presence of well-defined soft tissue abnormality, thickened cortex, and a relatively good interface between normal and diseased marrow. The appearance of osteomyelitis did not vary in different anatomic sites.

Osteomyelitis and pyogenic infection of the sacroiliac joint. MRI findings and review.

Acute pyogenic sacroiliac joint infection and osteomyelitis of adjacent bones often present with severe, poorly localized lower back, pelvic or hip pain. Five cases of sacroiliac joint infection or sacroiliac bone osteomyelitis were evaluated by MRI. MRI may be a helpful diagnostic tool to evaluate early changes of infection in the sacroiliac area. It is very sensitive for detecting bone marrow abnormalities; however, it is nonspecific and can not accurately differentiate osteomyelitis from sacroiliitis.

ALARA, Image Gently and CT-induced cancer

The term As Low As Reasonably Achievable (ALARA) goes back to articles in 1980, 1986 and 1999 [1–3]. In 2001, a group of inspired pediatric radiologists introduced the ALARA concept into routine clinical radiology practice [4–7]. The ALARA and the Image Gently campaigns have been very successful in achieving their goals of reducing unnecessary imaging and radiation exposure, inspiring the development of new technology, and expanding our understanding of measuring radiation dose in humans [6–15]. ALARA and Image Gently evolved from a belief that even if the true cancer risks of X-ray imaging were not known, a cautious approach of minimizing radiation was sensible. Althoughmost radiologists believe the cancer risks frommedical imaging are extremely small, if they exist at all, the media and some medical journals have so magnified and advertised this cancer risk that some patients and referring physicians may be avoiding medically indicated CT scans (Table 1). The objectives of this article are to make radiologists aware of the extensive adverse publicity that CT has received in respected media (television and newspapers) and in publications from non-radiologists. My hope is that, with this knowledge, pediatric radiologists can improve the care of their patients by being prepared to address questions from parents and referring physicians with honest reassuring answers. I will review and critique many of the misleading conclusions regarding cancer risk from CT that have appeared in the media and some journals. I will also review the historical background that led to a belief that data on the cancer incidence from the survivors of the atom bombs in Japan can be extrapolated back in a linear fashion to calculate the cancer risk from tiny radiation doses. This belief that no threshold exists for cancer risk from radiation is termed the linear no threshold theory. With new data from atom bomb survivors, this linear no threshold theory is being seriously challenged [16–20]. Finally, I will discuss recent epidemiological studies that have linked CT to cancer. These studies must be interpreted with great caution. I will provide the pediatric radiologist with information regarding real weaknesses in these studies that they can share with patients, parents and referring physicians.