Disseminated neuroblastoma in the nude rat. A xenograft model of human malignancy.

BACKGROUND: The overall survival of children with neuroblastoma remains less than 30% due to disease dissemination at the time of diagnosis. An animal model of neuroblastoma, with characteristics similar to those observed clinically in children, would be beneficial to investigations into the diverse biology of this tumor. The purpose of this study was (1) to develop a model of disseminated neuroblastoma in the nude rat by intracardiac injection of neuroblastoma cells derived from cell lines with different N-myc copy numbers; (2) to investigate the effect of age on tumor growth and dissemination; and (3) to assess progression of disease radiologically and correlate with autopsy findings. METHODS: Nude rats (n = 38), 5-13 weeks of age, underwent intracardiac injection of the human neuroblastoma cell lines IMR-32 with amplified N-myc oncogene and SKNSH with 1 N-myc copy. The animals were observed for at least six weeks for the development of tumor. Twelve rodents injected with IMR-32 cells underwent imaging studies including magnetic resonance imaging (MRI), skeletal radiographs, and indium-111(IN-111)-diethylenetriamine penta-acetic acid-D-Phe1-octreotide scintigraphy. Autopsies with standardized microscopic examinations were performed on all animals. RESULTS: Most of the nude rats (95%) developed neuroblastoma following intracardiac injection of neoplastic cells. Disseminated tumor was evident in 66% of animals. Anatomic sites of neuroblastoma growth were similar to those observed clinically in children, including adrenal glands, paraspinal ganglia, bone, bone marrow, and skin, but no tumor was identified in the liver. Disseminated disease occurred in more animals injected with IMR-32 (78% of animals) than with SKNSH cells (34% of animals) (P < 0.05). Tumor spread appeared to be age dependent; only rodents 5-8 weeks old at the time of injection developed disseminated disease when compared with animals 9 weeks of age or older (P < 0.0001). Radioreceptor scintigraphy demonstrated only pericardial tumor; MRI identified pericardial, adrenal gland, and subcutaneous neoplasms; only skeletal radiographs detected neuroblastoma in cortical bone. CONCLUSIONS: (1) Following intracardiac injection of human neuroblastoma cell lines into nude rats, a xenograft model of disseminated disease develops that closely parallels the malignant process in children. (2) Tumor dissemination is associated with the cell line that demonstrates N-myc amplification and with young age of the recipient at the time of injection. (3) Tumor growth and dissemination may be assessed radiologically. (4) This model of human malignancy may offer an opportunity to investigate the pathophysiologic mechanisms underlying tumor development and dissemination in advanced stage neuroblastoma.

Use of computed tomography in evaluation of acute respiratory distress in a 4.5-month-old with bronchogenic cyst.

A 4.5-month-old female presented with stridor and acute respiratory distress. Chest radiographs showed hyperinflation of the left lung. Computed tomography of the chest demonstrated a small bronchogenic cyst not clearly identified by other methods.

Parenteral nutrition with associated cholelithiasis: another iatrogenic disease of infants and children.

During the past decade, 246 infants and children treated at the Columbus Children's Hospital have required more than 4 weeks of parenteral nutrition (PN). Of the 178 survivors, 70 returned for evaluation. Sixty-eight either had adequate visualization of the gallbladder by ultrasound or had previous gallbladder surgery (39%). Of 68 children who did not survive, complete postmortem examinations or ultrasound studies were available for 16 (24%). A diagnosis of cholelithiasis was established in 11 of the 84 studied patients (13%). Six of these children (55%) have required cholecystectomy for relief of chronic abdominal pain, pancreatitis, or empyema of the gallbladder. One additional infant underwent cholecystostomy. Two of the four remaining patients are asymptomatic, one has episodes of abdominal colic, and one child expired of chronic hepatic insufficiency as a result of PN-associated cholestasis. Risk factors that predisposed these children to cholelithiasis included short bowel syndrome, lack of an ileocecal valve, and an increased number of abdominal operative procedures (P less than .05). Patients with biliary calculi also had a longer duration of parenteral feeding, and a higher incidence of both PN-associated cholestasis and necrotizing enterocolitis. The intergroup differences for these characteristics, however, did not achieve statistical significance. On the basis of this information, routine ultrasound examinations of the gallbladder are recommended for children maintained on PN for longer than 30 days. All patients presenting with abdominal pain who previously received PN should also be evaluated. Early elective cholecystectomy is suggested for children who develop PN-associated cholelithiasis.

Radiographic identification of ingested disc batteries.

Recently, the hazards posed by the accidental ingestion and impaction of small disc batteries have been widely publicized in the medical and lay press. These foreign bodies, when lodged in the esophagus, leak a caustic solution of 26 to 45% sodium or potassium hydroxide which can cause a burn injury to the esophagus in a very short period of time. Because of the considerable clinical morbidity and mortality from this foreign body, it becomes imperative for the radiologist to quickly and accurately identify disc batteries on plain radiographs. This communication offers a series of radiologic signs important in the identification of disc batteries. When viewed in an anterior projection, disc batteries demonstrate a double density shadow due to the bilaminar structure of the battery. On lateral view, the edges of most disc batteries are round and again present a step-off at the junction of the cathode and anode. These findings are differentiated from the more common esophageal foreign body of a coin which does not have a double density on frontal projection, has a much sharper edge and no visible step-off.

Diffuse hemangiomatosis of the colon.

We report extensive colonic hemangiomatosis in two young adults. In the first, the hemangioma contiguously involved the entire colon. In the second, a large venous angioma affected the bladder, rectosigmoid, and descending colon. Venous angioma, a variant of hemangioma, is frequently confused with cavernous hemangioma because of their similar histologic appearance. The angiographic features, however, may enable a more accurate preoperative diagnosis and prevent unwarranted biopsy. We review and put into perspective pertinent previous reports of cavernous and venous angioma.

Secondary ossification center of transverse process: a bone-scan normal variant.

This report describes the bone-scan appearance of significantly increased activity in a lumbar transverse process of a 15-year-old boy; we believe it represents a normal variant related to the secondary ossification center.

Mediastinal extramedullary plasmacytoma.

An asymptomatic 65-year-old woman was found to have a mediastinal mass on routine chest x-ray examination. The initial diagnosis of aneurysm of the thoracic aorta was excluded by a thoracic aortogram, and a plasmacytoma was discovered at exploratory operation.

Lymphocele: an unusual mass in the right upper quadrant.

A patient with a palpable right upper abdominal mass eight years after cholecystectomy was found to have a subhepatic lymphocele. Although this is an uncommon location, the presence of a sonolucent mass in an area of previous surgery suggests lymphocele.

Traumatic lumbar artery-inferior vena cava fistula.

A case is presented of a young man with small bowel and colon perforations secondary to an anterior abdominal knife wound who on followup examination had a lumbar artery-inferior vena cava fistula. This was closed successfully 8 weeks postinjury.

Decreased lung perfusion due to broncholithiasis.

Two patients each with symptoms of an endobronchial lesion showed decreased unilateral lung perfusion upon radionuclide imaging. Chest films were normal except for hilar lymph node calcifications. Bronchography and tomography revealed compression and obstruction of the bronchial tree by the calcified lymph nodes, accounting for the patients' symptoms. Incomplete bronchial obstruction or collateral air drift accounted for the normal appearance of the lungs on the PA chest films.

Erosion of the scapula by a benign lipoma: computed tomography diagnosis.

A lipoma eroding the scapula is diagnosed by computed tomography.

Hindgut duplication with rectovaginal fistula.

Complete colon duplication is an extremely rare congenital anomaly that occasionally presents diagnostic problems. This report presents a 23-year-old black woman with complete duplication of the colon and distal ileum, with termination of 1 colon into the vagina.