The paediatric thymus: recognising normal and ectopic thymic tissue.

The appearance of the paediatric thymus changes as the normal process of thymic involution occurs. Thymic tissue may be orthotopic within the anterior mediastinum or ectopically located along the course of its embryological development. The variable appearance of orthotopic and ectopic thymic tissue in children on imaging studies may lead to misinterpretation of the normal thymus as pathology. Recognition of normal thymic tissue can mitigate unnecessary further diagnostic testing and patient anxiety. In this review, we discuss the embryological development and anatomical variants of normal thymus, and demonstrate the multimodality imaging features of the normal thymus in children, including positron-emission tomography, and diffusion-weighted imaging and in- and opposed-phase imaging on magnetic resonance imaging. We demonstrate the normal thymus mimicking pathological processes and discuss features that distinguish normal thymus, including thymic rebound hyperplasia, from pathology.

EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment.

BACKGROUND: Four international study groups undertook a large study in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based on histological response. PATIENTS AND METHODS: Patients with resectable osteosarcoma aged ≤40 years were treated with the MAP regimen, comprising pre-operatively of two 5-week cycles of cisplatin 120 mg/m(2), doxorubicin 75 mg/m(2), methotrexate 12 g/m(2) × 2 (MAP) and post-operatively two further cycles of MAP and two cycles of just MA. Patients were randomised after surgery. Those with ≥10% viable tumour in the resected specimen received MAP or MAP with ifosfamide and etoposide. Those with <10% viable tumour were allocated to MAP or MAP followed by pegylated interferon. Longitudinal evaluation of quality of life was undertaken. RESULTS: Recruitment was completed to the largest osteosarcoma study to date in 75 months. Commencing March 2005, 2260 patients were registered from 326 centres across 17 countries. About 1334 of 2260 registered patients (59%) were randomised. Pre-operative chemotherapy was completed according to protocol in 94%. Grade 3-4 neutropenia affected 83% of cycles and 59% were complicated by infection. There were three (0.13%) deaths related to pre-operative chemotherapy. At definitive surgery, 50% of patients had at least 90% necrosis in the resected specimen. CONCLUSIONS: New models of collaboration are required to successfully conduct trials to improve outcomes of patients with rare cancers; EURAMOS-1 demonstrates achievability. Considerable regulatory, financial and operational challenges must be overcome to develop similar studies in the future. The trial is registered as NCT00134030 and ISRCTN 67613327.

Anatomical distribution of vertebral fractures: comparison of pediatric and adult spines.

SUMMARY: We compared the distribution of vertebral fractures in adults and children and found that fractures occurred in different locations in the two age groups. This likely relates to the different shape of the immature spine. INTRODUCTION: We hypothesized that the anatomical distribution of vertebral fractures (VF) would be different in children compared to adults. METHODS: We compared the distribution of VF defined using the Genant semi-quantitative method (GSQ method) in adults (N = 221; 545 fractures) and in children early in the course of glucocorticoid therapy (N = 44; 94 fractures). RESULTS: The average age in the adult cohort was 62.9 years (standard deviation (SD), 13.4 years), 26% was male, the mean lumbar spine Z-score was -1.0 (SD, 1.5), and the corresponding T-score was -2.4 (SD, 1.4). The pediatric cohort median age was 7.7 years (range, 2.1-16.6 years), the mean lumbar spine Z-score was -1.7 (SD, 1.5), 52% was male, and disease categories were acute lymphoblastic leukemia (66%), rheumatological conditions (21%), and nephrotic syndrome (14%). The VF distribution was biphasic in both populations, but the peaks differed in location. In adults, the peaks were at T7/T8 and at T12/L1. In children, the focus was higher in the thoracic spine, at T6/T7, and lower in the lumbar spine, at L1/L2. When children were assessed in two age-defined sub-groups, a biphasic VF distribution was seen in both, but the upward shift of the thoracic focus to T6 was observed only in the older group, with the highest rates of fracture present between ages 7 and 10 years. CONCLUSIONS: These results suggest that the anatomical distribution of VF differs between children and adults, perhaps relating to the different shape of the immature spine, notably the changing ratio of kyphosis to lordosis.

Nuclear medicine topics in pediatric musculoskeletal disease: techniques and applications.

Musculoskeletal scintigraphy has excellent sensitivity for the evaluation of benign disease in children. Using illustrative cases, a spectrum of techniques and applications of nuclear medicine studies for benign bone diseases are presented. An approach to the use and evaluation of bone density evaluation in children also is discussed.

Wound healing: captopril, an angiogenesis inhibitor, and Staphylococcus aureus peptidoglycan.

BACKGROUND: Captopril, an angiotensin-converting enzyme inhibitor, used for treating hypertension and heart failure, inhibits angiogenesis in the corneas of rats in response to basic fibroblast growth factor, slows the growth of experimental tumors in rats, and leads to the regression of Kaposi's sarcoma. Because angiogenesis is key to wound healing, we hypothesized that captopril would impair wound healing. We hypothesized also that because local application at operation of Staphylococcus aureus peptidoglycan (SaPG) increases angiogenesis and accelerates wound healing in rats, SaPG would prevent or ameliorate the postulated captopril-impaired wound healing. MATERIALS AND METHODS: In each experiment, rats were divided randomly into two groups: one drinking tap water, and the other, tap water containing 0.5 mg captopril/ml. All ate chow and drank ad libitum, pre-operatively (4-12 days) and postoperatively (7 days). In experiments 1 and 2, bilateral paravertebral 5.5-cm skin incisions were made aseptically (intraperitoneal sodium pentobarbital), and closed with interrupted No. 35 stainless-steel sutures. On one side, the wound was immediately inoculated with 157 microliter pyrogen-free isotonic saline and on the other side the wound was inoculated with 157 microliter saline containing 4.7 mg SaPG (860 microgram SaPG/cm incision). In the third experiment, polyvinyl alcohol (PVA) sponges (16-17 mg dry wt each) containing either 50 microliter saline or 0.5 mg SaPG in 50 microliter saline were implanted subcutaneously, two on each side, via 1-cm incisions closed with a single suture. In the fourth experiment, 5.5-cm bilateral skin incisions and subcutaneous implantation of PVA sponges were done as described but all sites were instilled with saline only. All rats were euthanized (CO(2) asphyxia) 7 days postoperatively. RESULTS: Wound breaking strength (WBS) of the saline-treated incisions was significantly higher (P < 0.001) in captopril-treated rats than in controls (172 +/- 13 g vs 105 +/- 6 g) in experiment 1 and higher, but not significantly in captopril-treated rats in experiment 2 (153 +/- 8 g vs 114 +/- 6 g) (PNS). SaPG inoculation of the incisions increased WBS significantly in both control and captopril-treated rats: 187 +/- 11 g vs 105 +/- 6 g (P < 0.001) and 283 +/- 16 g vs 172 +/- 13 g (P < 0.001), respectively, in experiment 1, and 217 +/- 13 g vs 114 +/- 6 g (P < 0.0001) (controls) and 266 +/- 17 g vs 153 +/- 8 g (captopril-treated rats) (P < 0.0001) in experiment 2. In experiment 3, subcutaneous PVA saline-inoculated sponge reparative tissue hydroxyproline (OHP) content was similar in control and captopril-treated rats, and SaPG inoculation increased reparative tissue OHP significantly in both groups: 2458 +/- 218 microgram/100 mg dry sponge vs 3869 +/- 230 microgram/100 mg (P < 0.001) (controls) and 2489 +/- 166 microgram/100 mg vs 4176 +/- 418 microgram/100 mg (P < 0.001) (captopril-treated rats). Histologically, angiogenesis and reparative tissue collagen were similar in control and captopril-treated rats, in both saline-inoculated and SaPG-inoculated sponges. In experiment 4 (all incisions and subcutaneous PVA sponges were saline-inoculated), there was no significant difference in WBS between control and captopril-treated rats (107 +/- 6 g vs 96 +/- 5 g, NS). PVA sponge reparative tissue OHP was significantly higher in captopril-treated rats: 3698 +/- 170 microgram/100 mg dry sponge vs 2534 +/- 100 microgram/100 mg (P < 0.0001). CONCLUSION: Unexpectedly, in four experiments, captopril did not inhibit WBS or PVA sponge reparative tissue angiogenesis or collagen accumulation; in fact, WBS was increased significantly in one of three experiments, and PVA sponge reparative tissue OHP was increased significantly in one of two experiments. Also, captopril did not interfere with the wound healing-accelerating effect of SaPG.

Laparoscopy as a cause of a false-positive Meckel's scan.

A new cause of a false-positive result of a Meckel's scan is reported. An 11-year-old girl had a 3-week history of constant right lower quadrant pain that was initially managed by laparoscopic appendectomy. A repeated laparoscopy for persistent pain was nondiagnostic. A missed Meckel's diverticulum was considered as the cause of this pain, which prompted a Meckel scan. This scan revealed a periumbilical focus of activity that was interpreted as a Meckel's diverticulum attached to the anterior abdominal wall by a band. The laparotomy showed no Meckel's diverticulum. The false-positive result of the Meckel scan may be the result of inflammation from the periumbilical laparoscopic port site.

The DMSA scan in paediatric urinary tract infection.

The objective of the present paper was to review the use of the dimercaptosuccinic acid (DMSA) scan in urinary tract infection at British Columbia's Children's Hospital to determine the frequency of cortical defects and the association between vesico-ureteric reflux and the presence of cortical defects in children with urinary tract infection. A total of 129 consecutive children with a urinary tract infection referred for a DMSA scan in a 2-year period (January 1992-January 1994) were retrospectively studied. The results were analysed in terms of kidneys, and the incidence of cortical defects was determined. Eighty-eight patients (68%) had a radiographic micturating cysto-urethrogram within 6 months of the DMSA scan, and in this group the relationship of defects with vesico-ureteric reflux was determined. Overall, 81/258 (31%) of kidneys had a cortical defect on a DMSA scan. Of those who had a micturating cysto-urethrogram, 53/176 (30%) kidneys had vesico-ureteric reflux, and of those that had reflux, 21/53 (40%) had a cortical defect on a DMSA scan. In the group of children without reflux, 38/123 (31%) had a cortical defect. Renal cortical scan defects are common findings in paediatric urinary infection, and frequently occur in the absence of vesico-ureteric reflux. These defects represent either established scars or acute pyelonephritis that can proceed to scarring. The micturating cysto-urethrogram alone is insufficient as a screening modality to identify those kidneys at risk of renal scarring.

Hepatobiliary scintigraphy in children.

Hepatobiliary scintigraphy using iminodiacetic (IDA) radiopharmaceuticals provides clinically useful information on the function of the biliary tract in a variety of pathological processes in children, including neonatal jaundice, gallbladder dysfunction, trauma, and liver transplantation. Phenobarbital premedication (5 mg/kg per day for a minimum of 5 days in divided doses) is used in infants who are being examined for neonatal jaundice to increase the accuracy of 99mTc-IDA scintigraphy in differentiating extrahepatic biliary atresia from neonatal hepatitis. Biliary atresia can be ruled out in an infant if a patent biliary tree is shown with passage of activity into the bowel. If no radiopharmaceutical is noted in the bowel on imaging up to 24 hours, distinction between severe hepatocellular disease and biliary atresia cannot be made. The literature reports 91% accuracy, 97% sensitivity, and 82% specificity for hepatobiliary imaging in the diagnosis of biliary atresia. The impairment of both intrahepatic and extrahepatic biliary drainage is an important cause of liver disease in cystic fibrosis. Hepatobiliary scintigraphy in cystic fibrosis has shown characteristic patterns of dilatation of mainly the left hepatic duct, narrowing of the distal common bile duct, gallbladder dysfunction, and delayed bowel transit. Cholecystitis in children may be acalculous. Sensitivity and specificity for the scintigraphic diagnosis of acute acalculous cholecystitis is reported to range from 68% to 93% and 38% to 93%, respectively. Cholescintigraphy in a suspected bile leak provides information generally not available with other techniques, except for direct cholangiography. If the amount of intraperitoneal accumulation of the tracer is greater than that entering the gastrointestinal tract, surgery is usually indicated. Hepatobiliary imaging in children who have undergone liver transplantation will assess graft vascularity, parenchymal function, biliary drainage, presence of a leak, and obstruction.

Obstructive lung disease in children after allogeneic bone marrow transplantation: evaluation with high-resolution CT.

OBJECTIVE: Obstructive lung disease is a major complication of bone marrow transplantation related to graft-versus-host disease. The purpose of this study was to determine the usefulness of high-resolution CT to evaluate obstructive lung disease occurring in children after bone marrow transplantation. MATERIALS AND METHODS: Ten high-resolution CT scans of the lungs were obtained in seven children who developed chronic obstructive lung disease after bone marrow transplantation. All seven patients had chronic graft-versus-host disease. Spirometry, the gold standard test, confirmed airflow obstruction in each case, five prior to high-resolution CT. Two patients were too young to have spirometry until 10 and 15 months respectively after successful high-resolution CT. Selected images from these studies were randomized with similar images from five control subjects and reviewed blindly. All images from scans in patients with obstructive lung disease were analyzed retrospectively for parenchymal hypoattenuation, bronchial dilatation, bronchial wall thickening, and abnormal parenchymal opacity. Expiratory air-trapping was assessed on cine high-resolution CT done in four cases. RESULTS: Three blinded observers each correctly identified all five controls among 15 high-resolution CT examinations. No scan from a patient with obstructive lung disease was considered normal. Areas of parenchymal hypoattenuation affected 35 of 35 lobes of the lung. Expiratory air-trapping was shown by cine high-resolution CT. Subsegmental or segmental bronchial dilatation was seen in 23 of 25 lobes in five patients. Bronchial wall thickening was not a prominent feature. Increasing abnormality was demonstrated in three patients on follow-up high-resolution CT. The high-resolution CT abnormalities were similar to those reported in patients with bronchiolitis obliterans. CONCLUSION: High-resolution CT of the lungs can show extensive abnormality in children who develop chronic obstructive lung disease after bone marrow transplantation. High-resolution CT is a useful noninvasive technique in the evaluation of this disease.

Thallium-201 for oncological imaging in children.

Many pediatric centers are beginning to accumulate a large experience in the use of thallium-201 (201Tl) imaging with 201Tl requires a state-of-the-art high-resolution gamma camera computer system with single photon emission computed tomography (SPECT) capability and a physician-directed tailored examination. Tumor imaging with 201Tl, with its multifactorial localization mechanisms that are different from those for gallium-67, offers a distinct advantage over gallium tumor imaging with a short total imaging time. Tumors are variable in avidity and intensity of thallium uptake. Primary and metastatic disease can be detected with 201Tl scintigraphy. Baseline pretreatment determination of thallium avidity is crucial to its efficacy in therapeutic response assessment. Adjunctive SPECT imaging provides greater sensitivity for lesion detection and direct comparison of physiology (thallium uptake) with anatomy (computed tomography and magnetic resonance imaging). The sensitivity and specificity for detection of pediatric brain tumors has been reported as 77% and 93%, respectively. Thallium-201 brain SPECT also provides a less expensive and more readily available alternative to positron emission tomography for assessing the functional state of pediatric brain tumors. Extremity osteogenic sarcoma and Ewing's sarcoma have 100% sensitivity for 201Tl uptake pretreatment. Early results confirm an association between 201Tl uptake and histological tumor response. The determination of residual/recurrent disease versus thymic rebound and other nonneoplastic change in thallium-avid lymphoma, rhabdomyosarcoma, and germ cell tumors that involve the thorax can be confirmed with a 201Tl SPECT examination. Soft-tissue tumors elsewhere in the body may be detected with 201Tl scintigraphy. Thallium-201 does not exhibit 100% specificity for tumors. False-positive 201Tl uptake has been seen in histiocytosis X, benign bone tumors, stress fractures, and inflammation.

Lung volumes, mechanics, and perfusion after pulmonary resection in infancy.

Partial pulmonary resection in early childhood is well tolerated. Although long-term outcome has been described in several follow-up studies, almost no information is available on postoperative lung perfusion. We studied 14 patients 3 to 20 years (mean, 11.6 years) after they underwent partial pulmonary resection at 1 week to 30 months of age (mean, 6.8 months). We examined development, pulmonary function, endurance, radiographs and ventilation-perfusion scans. We used predicted pulmonary function test values, which were corrected for the relative amount of lung removed and called predicted-corrected values. We hypothesized that the remaining lung would have altered ventilation-perfusion characteristics. We found no abnormalities in the patients' physical development. Most children had abnormal regional ventilation, but normal equilibration occurred; five patients had gas retention; all had decreased perfusion to the area of resection; nine patients showed ventilation-perfusion mismatch characterized by dead-space ventilation. Lung volumes were within the predicted range in 12 patients. Residual volume and functional residual capacity were larger than predicted-corrected values in most patients but residual volume in relation to total lung capacity was at or below normal in 6 of 11 and did not correlate with the amount of lung removed. Most patients had prolonged expiratory flows. We conclude that lung resection in early childhood leads to good functional recovery. However, decreased expiratory flows, regional ventilation abnormalities, and decreased perfusion suggest dysplastic parenchyma and vascular bed in the area of resection.

Preliminary report: imaging of Kaposi sarcoma and lymphoma in AIDS with indium-111-labelled liposomes.

Kaposi sarcoma and malignant lymphoma were successfully imaged with high purity liposomes containing indium-111 in two patients with AIDS. Gamma camera images of the patient with Kaposi sarcoma showed four discrete lesions along the left foot and calf with no foci along the right foot, and no uptake into clinically enlarged but non-neoplastic lymph nodes. The spread of the Kaposi sarcoma was proximal along the leg. The neoplastic cervical lymph nodes in the second patient who had large-cell diffuse intermediate grade lymphoma were also imaged successfully. Since Kaposi sarcoma and lymphoma frequently involve occult sites, liposome imaging may prove useful in the diagnosis and management of these diseases.

Neonatal renomegaly.

A retrospective clinical review was done to study the value of ultrasound and renography in the investigation of 100 neonates with renomegaly. Abnormalities in 73 patients were detected antenatally with ultrasonography. Of the neonates 47 had lower urinary tract pathological conditions and ultrasound was more than 90 per cent accurate in identifying the accompanying ureteral dilatation. A total of 53 neonates had upper tract anomalies (ureteropelvic junction obstruction or cystic dysplasia). With ultrasonography the degree of pyelocaliectasis in patients with ureteropelvic junction obstruction was classified as mild (22 units), moderate (13) or severe (7). Initial treatment and followup were reviewed to study the clinical course of neonates with mild to moderate degrees of pyelocaliectasis followed nonoperatively, and to determine whether the diuretic renogram had a predictive role in identifying which kidneys were most likely to deteriorate.

The immotile cilia syndrome: radiological manifestations.

The immotile cilia syndrome (ICS) is an uncommon disorder characterized by specific and genetically determined defects of cilia that cause upper and lower respiratory disease. We reviewed the radiographic patterns in 30 patients who had ICS (15 females, 15 males) and ranged in age from newborn to 26 years. Except for two neonates, sinusitis and otitis were present in all patients. Chest radiographic abnormalities, universally present, included bronchial wall thickening, hyper-inflation, segmental atelectasis or consolidation, and segmental bronchiectasis. Situs inversus, present in 50% (7 females, 8 males), was not an essential part of this disorder. Radiologically, the disease progresses from bronchial wall thickening with or without hyperinflation, to increasing hyperinflation plus parenchymal changes including segmental atelectasis, consolidation, and bronchiectasis. There is also a predilection for anatomic middle lobe abnormalities. The radiological appearance and clinical state have similarities to cystic fibrosis, although they are less severe and less progressive. ICS should be considered in the differential diagnosis of slowly progressive chronic lung disease, sinusitis, and otitis.