An orthotopic metastatic prostate cancer model in SCID mice via grafting of a transplantable human prostate tumor line

Metastasis is the major cause of prostate cancer deaths and there is a need for clinically relevant in vivo models allowing elucidation of molecular and cellular mechanisms underlying metastatic behavior. Here we describe the development of a new in vivo model system for metastatic prostate cancer. Pieces of prostate cancer tissue from a patient were grafted in testosterone-supplemented male NOD-SCID mice at the subrenal capsule graft site permitting high tumor take rates. After five serial transplantations, the tumor tissues were grafted into mouse prostates. Resulting tumors and suspected metastatic lesions were subjected to histopathological and immunohistochemical analysis. Samples of metastatic tissue were regrafted in mouse anterior prostates and their growth and spread examined, leading to isolation from lymph nodes of a metastatic subline, PCa1-met. Orthotopic grafting of PCa1-met tissue in 47 hosts led in all cases to metastases to multiple organs (lymph nodes, lung, liver, kidney, spleen and, notably, bone). Histopathological analysis showed strong similarity between orthotopic grafts and their metastases. The latter were of human origin as indicated by immunostaining using antibodies against human mitochondria, androgen receptor, prostate-specific antigen and Ki-67. Spectral karyotyping showed few chromosomal alterations in the PCa1-met subline. This study indicates that transplantable subrenal capsule xenografts of human prostate cancer tissue in NOD-SCID mice can, as distinct from primary cancer tissue, be successfully grown in the orthotopic site. Orthotopic xenografts of the transplantable tumor lines and metastatic sublines can be used for studying various aspects of metastatic prostate cancer, including metastasis to bone.     

Neonatal adrenal congestion: a sonographic-pathologic correlation

We reviewed the clinical, sonographic and pathologic findings in eight neonates in whom diffuse enlargement and abnormal echogenicity of the adrenal glands was documented sonographically. Four of the patients suffered from perinatal asphyxia and two others required mechanical ventilation for other reasons. Six patients died and one suffers from severe development delay, cerebral palsy and failure to thrive. Sonographically, the glands were enlarged, their surface was smooth and there was loss of the central echogenic stripe. Diffuse sinusoidal congestion was found histologically in all five in whom autopsies were performed. These sonographic findings represent part of the spectrum of adrenal changes in neonatal asphyxia and other causes of perinatal stress, and may be associated with poor outcome because of other sequelae of asphyxia. Received: 12 March 1998 Accepted: 8 June 1998     

Microvillous Inclusion Disease: Report of a Case with Atypical Features

Microvillous inclusion disease is a rare lethal disorder characterized by intractable, severe, watery diarrhea beginning in early infancy. The underlying defect is thought to be an autosomal recessive genetic abnormality resulting in defective brush-border assembly and differentiation. Normally, this diagnosis is easily established through the electron microscopic demonstration of characteristic microvilli-lined inclusions lying within the apical cytoplasm of surface enterocytes. In a small number of patients appearing to have microvillous inclusion disease it has not proven possible to demonstrate the typical inclusions. The existence of another entity, termed intestinal microvillous dystrophy, has been proposed to account for such occurrences. This assertion was founded in large part upon the observation that the few subjects studied all displayed a slightly atypical clinical presentation. The case now being presented exhibited the morphologic features ascribed to intestinal microvillous dystrophy but had a clinical presentation that was entirely typical of microvillous inclusion disease. It serves thus to conceptually unite intestinal microvillous dystrophy with microvillous inclusion disease.     

Gastral antral biopsy in the differentiation of pediatric colitides

OBJECTIVES: Differentiation of Crohn's disease (CD) from ulcerative colitis (UC) is problematic, primarily when inflammation is confined to the colon. In a historical cohort study, we evaluated the usefulness of baseline gastric antral biopsies in the differentiation of pediatric chronic colitides. METHODS: During initial investigation for suspected inflammatory bowel disease, 39 children and adolescents with colitis but normal small bowel radiography underwent pretreatment upper endoscopy concurrently with colonoscopy. Two reviewers assigned a colonoscopic diagnosis (colonic CD, UC, or indeterminate colitis) based on the macroscopic and microscopic appearances of the colonic mucosa. Antral histological findings were compared between groups using Fisher's exact test. RESULTS: Five (14%) of colonoscopic diagnoses (four indeterminate, one UC) were changed to CD by the finding of granulomatous inflammation in antral biopsies. Nonspecific antral gastritis was found in similar proportions of children and adolescents with Crohn's colitis and UC (92% vs 75%). Focal antral gastritis was more common in patients with Crohn's colitis than UC (52% vs 8%). CONCLUSIONS: Nonspecific antral gastritis is common in all forms of chronic colitis. Nevertheless, upper gastrointestinal endoscopy with biopsy is useful in the differentiation of inflammatory bowel disease confined to the colon, particularly when colonoscopic findings are indeterminate.     

Pathological Features of Multiple Endocrine Neoplasia Type IIb in Childhood

The features of two patients with multiple endocrine neoplasia type IIb are described. Patient 1, a 9-year-old boy with marfanoid features, presented with chronic constipation and failure to thrive since infancy. Patient 2, a 12-year-old boy with marfanoid features, presented with a five-year history of persistent cervical lymphadenopathy. In patient 1, the myenteric and submucosal nerve plexuses at all levels of the small and large intestines were comprised of diffusely disorganized, hyperplastic, mature ganglion cells and nonmyelinated nerve fibers. Nerve plexus dissection with morphometric analysis showed marked thickening of the myenteric plexus with a quantitative increase in neural tissue. Patient 2 had a submucosal neuroma of the tongue. Both patients had occult medullary thyroid carcinoma, and patient 2 had cervical lymph node metastases. Both neoplasms showed positive staining for cytokeratin, carcinoembryonic antigen, calcitonin, bombesin, chromogranin, serotonin, and Leu 7. Electron microscopy showed membrane-bound, intermediate-sized, dense-core neurosecretory granules in tumor cells. In patient 2, calcitonin-positive amyloid was present with localization of calcitonin by immunoelectron microscopy to cytoplasmic secretory granules and to extracellular amyloid fibrils. These cases illustrate the potential for missed or delayed diagnosis in multiple endocrine neoplasia syndromes.     

Liver disease in neonatal lupus erythematosus

We report the cases of neonatal lupus erythematosus associated with significant hepatic involvement in three living infants and in one infant who died 3 hours after delivery. The three living infants had neonatal cholestasis as a major component of their clinical findings. Pathologic changes included giant cell transformation, ductal obstruction, and extramedullary hematopoiesis. Liver involvement has been noted incidentally in children with neonatal lupus erythematosus, but it has generally been attributed to hemodynamic compromise as a result of congenital heart block or systemic toxic reactions. We speculate that neonatal hepatitis proceeding to hepatic fibrosis may occur in neonatal lupus erythematosus, analogous to the occurrence of "idiopathic" congenital heart block. The neonatal hepatitis associated with neonatal lupus erythematosus is a form distinguishable from the "idiopathic" group. Liver involvement may be more common than was previously recognized, and prospective studies to look for maternal autoantibodies in idiopathic neonatal liver disease should be undertaken.     

Biliary disease in metachromatic leukodystrophy

Pediatric Radiology - This paper illustrates the previously unreported sonographic changes in the biliary tract in metachromatic leukodystrophy (MLD). Gallbladder wall thickening due to sulfatide...     

Reye's syndrome: preservation of mitochondrial enzymes in brain and muscle compared with liver.

The activities of five mitochondrial enzymes tested in liver from patients with Reye's syndrome were measured. Citrate synthase, glutamic dehydrogenase, succinic dehydrogenase, pyruvate carboxylase, and pyruvate dehydrogenase were all outside of the range shown by control samples and well below them in activity. The activity of two extramitochondrial enzymes, glucose-6-phosphatase, which is a microsomal enzyme, and fructose-1,6-diphosphatase, which is a soluble enzyme, were in the normal range in samples from Reye's syndrome patients. In both muscle and brain the activities of the mitochondrial enzyme, citrate synthase, glutamic dehydrogenase, and succinic dehydrogenase were all within the control range. Pyruvate dehydrogenase was found to be normal in muscle from these patients.