Type I Gaucher disease: extraosseous extension of skeletal disease

Objective. To investigate the frequency and morphology of extraosseous extension in patients with Gaucher disease type I. Design and patients. MRI examinations of the lower extremities were analyzed in 70 patients with Gaucher disease type I. Additionally, the thoracic spine and the midface were investigated on MRI in two patients. Results. Four cases are presented in which patients with Gaucher disease type I and severe skeletal involvement developed destruction or protrusion of the cortex with extraosseous extension into soft tissues. In one patient, Gaucher cell deposits destroyed the cortex of the mandible and extended into the masseter muscle. In the second patient, multiple paravertebral masses with localized destruction of the cortex were apparent in the thoracic spine. In the third and fourth patient, cortical destruction with extraosseous tissue extending into soft tissues was seen in the lower limbs. Conclusions. Extraosseous extension is a rare manifestation of Gaucher bone disease. While an increased risk of cancer, especially hematopoietic in origin, is known in patients with Gaucher disease, these extraosseous benign manifestations that may mimic malignant processes should be considered in the differential diagnosis of extraosseous extension into soft tissues. A narrow neck of tissue was apparent in all cases connecting bone and extraosseous extensions. Received: 19 July 1999 Revision requested: 8 September 1999 Revision received: 7 October 1999 Accepted: 14 October 1999     

COMPARATIVE METABOLISM OF LOW CONCENTRATIONS OF BUTADIENE AND ITS MONOEPOXIDE IN HUMAN AND MONKEY HEPATIC MICROSOMES

The chronic (2-yr) inhalation toxicity of 1,3-butadiene (BD), a chemical used in large quantities to make rubber and plastics, differs greatly between mice and rats. Mice develop lung tumors after exposures to concentrations as low as 6.25 ppm, whereas rats develop mammary tumors only after exposures to 1000-8000 ppm BD. Extensive research has been carried out to determine where humans fit into this susceptibility range. Species differences in rates of metabolism of BD have been noted, but inconsistencies in metabolism data from different laboratories and some problems in the fit of physiologically based pharmacokinetic (PBPK) models with experimental data have left uncertainties. The experiments reported here are intended to clarify the issue of human metabolism of BD and to determine if metabolism of BD in cynomolgus monkeys is similar enough to metabolism in humans to use in vivo data from monkeys for PBPK modeling. The results indicate that for the reactions studied (oxidation of BD to the mono- and diepoxide), BD is metabolized substantially the same in monkey and human hepatic microsomes. The human metabolism data agreed with that reported earlier when the in vitro metabolism of BD was studied at low BD concentrations. Finally, BD at high concentrations was found to inhibit the further oxidation of its metabolite, the monoepoxide. Incorporation of this information on the competition between BD and its first oxidation product for CYP2E1 should improve the fit of PBPK models.     

Impact of Multifocality and Multilocation of Positive Surgical Margin After Radical Prostatectomy on Predicting Oncological Outcome

Objective

To assess the impact of focality and location of positive surgical margins (PSM) on long-term outcomes after radical prostatectomy (RP) for prostate cancer (PCa), including biochemical recurrence (BCR), metastasis and overall mortality.