Faculty Bibliography

Acinar cell carcinoma (ACC) is a rare tumor that constitutes 1% of pancreatic neoplasms. ACC is defined as a carcinoma exhibiting pancreatic enzyme production by neoplastic cells. Clinical presentation is usually related to either local spread or metastasis. In this Radiology-Pathology Conference, the clinical presentation and imaging findings of a patient with ACC of the pancreas, along with the differential diagnosis, are reviewed.

In the pediatric population, clear cell meningiomas are more frequently intracranial than intraspinal in location. Tumors recur in up to 40% of cases within 15 postoperative months and are often managed with repeated resection with or without radiation therapy. The management strategy for adults with clear cell meningiomas involving the lumbar spinal canal (cauda equina) is less clearly defined. A 41-year-old woman presented with mild, right greater than left, lower extremity paresis. An enhanced magnetic resonance (MR) scan revealed a homogeneously enhancing intradural lesion filling the spinal canal at the L3-L4 level. Preoperative noncontrast MR studies of the brain and cervical and thoracic spine were negative. An L2-L5 laminectomy was performed for gross total excision of the intradural lesion, which was adherent to one nerve root of the cauda equina. Frozen-section diagnosis confirmed clear cell tumor. Differential diagnoses included meningioma versus renal cell carcinoma. Negative postoperative chest, abdominal, and pelvic computed tomography studies ruled out tumor of renal cell origin. Enhanced MR studies of the neuraxis proved negative. Consultations with multiple oncologists and radiation therapists recommended neither radiation nor chemotherapy following this initial surgery. She remains disease-free 1 year postoperatively. The high recurrence rate for clear cell meningiomas in children requires repeated tumor resection with or without secondary radiation therapy. Following gross total resection of lumbar tumors in adults, reserving radiation therapy for secondary recurrences provides optimal management.

This study assesses the vulnerability of fetal guinea pig heart to metabolic changes during acute nonlethal in utero hypoxia. Guinea pigs (50-55 days gestation) were exposed to 7% O2 for 2 h and room air for 4 h. Fetal hearts were harvested before hypoxia, at the end of hypoxia, and 4 h after hypoxia, and analyzed for: apoptosis (TUNEL), histology, lipid peroxidation and ATP. A group of posthypoxic dams was taken to gestation. Within 48 h postpartum, the function of neonatal hearts was tested and cerebral histology examined. Fetal heart ATP was decreased by 27% at the end of hypoxia and by 32% 4 h after hypoxia. The lipid peroxides, 4-hydroxynonenal and malondialdehyde, were decreased by 37 and 46%, respectively, by 4 h after hypoxia. The apoptotic index increased from 2% in prehypoxic hearts to 8.4% by 4 h after hypoxia. Fetal heart morphology was unremarkable. Postpartum neonatal cardiac function was not affected and cerebral histology was unremarkable. These results support the conclusion that nonlethal in utero hypoxia has acute effects on the fetal heart but no persistent cardiac or cerebral effects in the postpartum neonate

Despite the widespread use of exogenous surfactant, acute and chronic lung injury continues to be a major cause of morbidity in preterm infants. CC10 is a protein produced by Clara cells that inhibits phospholipase A2 and has anti-inflammatory and antifibrotic properties. We studied whether intratracheal (IT) recombinant human Clara cell protein (rhCC10) could safely minimize lung injury in a newborn piglet model of acute lung injury. Twenty-nine newborn piglets were given Survanta and then ventilated for 48 h receiving the following: room air (group 1); 100% O2 (group 2); or 100% O2 and 25, 5, or 1 mg/kg (groups 3, 4, and 5, respectively) of IT rhCC10 (diluted to 2 mL/kg with saline) at time 0. Laboratory studies, oxygen ratios, static pressure-volume curves, bronchoalveolar lavage (for inflammatory markers), and histologic analyses were performed over the 48-h study period. Pulmonary compliance and oxygenation were significantly improved in animals receiving 5 mg/kg IT rhCC10 compared with room air and 100% O2 controls (p < 0.004 and p < 0.05, respectively, ANOVA). Reductions in inflammatory markers were seen in animals receiving rhCC10, although changes did not reach statistical significance. No significant toxicity was noted. rhCC10 appeared safe and improved pulmonary function in this newborn piglet model of hyperoxic lung injury. We speculate that rhCC10 may represent a promising therapy for the prevention of lung injury in preterm infants.

To study the influence of cAMP on cellular responses to nerve growth factor (NGF) and to use elevation of intracellular cAMP to probe the NGF mechanism, cultured PC12 pheochromocytoma cells were exposed to forskolin and cholera toxin. As in other cell types, the latter agents greatly increased PC12 cell cAMP levels. Such treatment also brought about a reversible, dose-dependent suppression of NGF-promoted regeneration of neurites. In support of the role of cAMP in this effect, regeneration blockage by forskolin was potentiated by phosphodiesterase inhibitors. When tested on NGF-stimulated initiation of process outgrowth, cholera toxin and forskolin exerted a dual effect. As in previous studies, these drugs, when applied along with NGF, significantly enhanced the initial formation of short cytoplasmic extensions. However, after approximately 3 d of NGF exposure, at which time such extensions begin to acquire the morphological and ultrastructural features of neurites, these agents suppressed process outgrowth. That is, the neurites were fewer in number, significantly less branched, and much shorter than in control cultures. Such changes also occurred when these drugs were added to cultures that had been pretreated with NGF alone. Whereas forskolin and cholera toxin affect the formation and regeneration of neurites, these drugs did not interfere with the short-latency, transient changes in surface morphology that are triggered by NGF, nor did they inhibit transcription-dependent priming. In contrast, the rapidly occurring NGF-induced phosphorylation of tyrosine hydroxylase was suppressed. Moreover, forskolin and cholera toxin rapidly and selectively blocked the NGF-promoted phosphorylation of a set of microtubule-associated proteins known as chartins. Previous observations have suggested a causal relationship between NGF-induced chartin microtubule-associated protein phosphorylation and the formation and outgrowth of neurites. This is supported by the present data and provides a possible mechanism whereby elevated cAMP may interfere with neurite growth and regeneration.