Amifostine (Ethyol) as modulator of hepatic and biliary toxicity from intraarterial hepatic chemoembolization: results of a phase I study.

BACKGROUND/AIMS: Hepatic and biliary toxicity are still significant problems after intraarterial hepatic chemoembolization for liver metastases from large bowel cancers. In about 30-60% of the patients hepatic and biliary toxicity are the limiting aspects of intraarterial hepatic chemoembolization and exclude a lot of patients from a repeated beneficial treatment. Amifostine (Ethyol) is a prodrug that must be dephosphorylated to the free thiol in which form it can detoxify free oxygen radicals generated by radiation, hypoxia and by drugs such anthracyclines, platinum analogues and alkylating agents. Amifostine as inactive prodrug is primarily metabolized at the tissue site by membrane alkaline phosphatase, which is highly active in the cell membranes of normal endothelial cells and biliary tree cells but not in the cell membranes and neovascular capillaries of tumor. When dephosphorylated to WR-1065, amifostine is rapidly taken up into normal liver cells by a carrier-mediated facilitated diffusion transport process. The resulting high thiol content in normal liver tissue (biliary cells and hepatocytes) compared with the negligible concentration in liver metastases from large bowel cancers probably provides for selective drug resistance to intraarterial hepatic chemoembolization protecting normal tissue and allowing full therapeutic effect on tumor. METHODOLOGY: From May 1997 we planned a phase I study in patients receiving intraarterial hepatic chemoembolization for liver metastases from large bowel cancers. We started at 200 mg/m2 dissolved in 250 cc of normal saline given in 15 min in the intrahepatic artery 20 min before an intraarterial hepatic chemoembolization consisting of mitomycin 10 mg/m2, epirubicin-50, cisplatin-60 diluted in 10 mL of contrast media, mixed in 15 mL of lipiodol UF followed by a gelfoam powder solution until stagnation of the flow. The escalating dose, every 3 patients, was: 200 mg/m2, 250 mg/m2, 300 mg/m2, 350 mg/m2. RESULTS: Toxicity has been observed at 350 mg/m2: 1 patient reported transient hypotension (Blood pressure 70/50 mm Hg), 1 patient had skin flushing and dyspnoea. 300 mg/m2 are well tolerated and seem to reduce the level of transaminases, lactic acid dehydrogenase, and gamma-glutamyl transferase. Also the duration of necrotic damage, always observed after intraarterial hepatic chemoembolization, seems shorter compared with historical controls. CONCLUSIONS: Amifostine can be certainly administered at 300 mg/m2 as intraarterial infusion and could be a significant step to ameliorate the therapeutic ratio of intraarterial hepatic chemoembolization.

[The disease of beta 2-amyloid deposition in the differential diagnosis of juxta-articular subchondral geode lesions]. / La malattia da depositi di beta-2 amiloide nella diagnosi differenziale delle lesioni geodiche subcondrali iuxta-articolari.

Beta-2 amyloidosis deposition is a new type of amyloidosis recently observed in long-term hemodialysis patients. One of the major osteoarticular complications of this disease is the appearance of subchondral bone cysts. In this paper the radiologic features of such radiolucencies are described and the criteria are outlined of the differential diagnosis from the geodes found in other arthropathies or para-physiologic conditions. The importance of the status of the joint space is stressed: on the basis of its patterns, arthropathies may be grouped as follows: inhomogeneous space narrowing in degenerative arthritis; homogeneous space narrowing in inflammatory arthritis; normal or nearly normal joint space if there is no/not-prevalent involvement of articular cartilage.

["Cupid's bow" contour of the lumbar vertebrae]. / Il profilo ad "arco di Cupido" delle vertebre lombari.

The cortical margin of the inferior end plate of lumbar vertebral bodies, in the frontal projection, frequently simulates the curvature of a bow, aimed cephalad. On lateral view, the two concavities are superimposed and lie in the posterior portion of the vertebral body. The aspect, called "Cupid's bow" must be considered a normal anatomic variant and should not be confused with diseases affecting the spine. The incidence and degree of the finding are discussed.