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• W3113171624 abstract "Samuels LD, Grosfeld JL, Kartha M. Radiation hepatitis in children. J Pediatr 1971;78:68-73. Fifty years ago, liver toxicity from radiation therapy was considered a rare phenomenon, as hepatic radioresistance was a broadly accepted principle. This misguided tenet was based on faulty assumptions that hepatocytes were inherently protected in that they existed mainly in interphase of the cell cycle and that radiation primarily affected the bile ducts.1Alati T. Van Cleeff M. Strom S.C. Jirtle R.L. Radiation sensitivity of adult human parenchymal hepatocytes.Radiat Res. 1988; 115: 152-160Crossref PubMed Scopus (28) Google Scholar The first reports of radiation hepatitis in children, now known as radiation-induced liver disease (RILD), emerged in the 1960s. In 1971, Samuels et al in The Journal described 2 cases of severe liver damage, detected on radioisotope scans and characterized acutely by severe interstitial hemorrhage and congestion and chronically by fibrosis and atrophy following hepatic radiation exposure.2Samuels L.D. Grosfeld J.L. Kartha M. Radiation hepatitis in children.J Pediatr. 1971; 78: 68-73Abstract Full Text PDF PubMed Scopus (5) Google Scholar Today, RILD is a commonly recognized subacute form of liver injury resulting from radiation therapy. Both “classic” and “non-classic” forms are described, the former presenting within 4 months of radiation therapy with hepatomegaly, anicteric ascites, and isolated alkaline phosphatase elevation.3Munoz-Schuffenegger P. Ng S. Dawson L.A. Radiation-induced liver toxicity.Semin Radiat Oncol. 2017; 27: 350-357Crossref PubMed Scopus (30) Google Scholar This is thought to be due to a veno-occlusive process, morphologically characterized by complete obliteration of central vein lumina by erythrocytes trapped in a dense network of reticulin and collagen fibers. Centrilobular hepatocytes are largely absent, a presumed result of hypoxic injury.4Fajardo L.F. Colby T.V. Pathogenesis of veno-occlusive liver disease after radiation.Arch Pathol Lab Med. 1980; 104: 584-588PubMed Google Scholar Non-classic RILD, although more common, is less understood mechanistically but may involve the loss of regenerating hepatocytes and reactivation of underlying liver diseases such as viral hepatitis in select populations.5Guha C. Kavanagh B.D. Hepatic radiation toxicity: avoidance and amelioration.Semin Radiat Oncol. 2011; 21: 256-263Crossref PubMed Scopus (131) Google Scholar Non-classic RILD most commonly manifests as a general decline in liver function, markedly elevated aminotransferase levels (≥5 × upper limit of normal), or jaundice within 3 months of radiation therapy.3Munoz-Schuffenegger P. Ng S. Dawson L.A. Radiation-induced liver toxicity.Semin Radiat Oncol. 2017; 27: 350-357Crossref PubMed Scopus (30) Google Scholar To date, no pharmacotherapy is available that specifically targets mechanisms driving RILD development, and treatment is aimed at symptom control and supportive care. In this sense, little has changed since the report of Samuels et al. Where advancements are evident concern the general recognition of RILD and hepatic protective strategies that likely would have prevented, or ameliorated, the condition. Neither case described was affected by diseases that required direct hepatic radiation exposure. As such, modern practice would have implemented radiation-minimization strategies to protect the liver. Still, even if the cases had required direct liver radiation, for example, hepatocellular carcinoma or metastasis, current understanding of dose–toxicity relationships and advances in the planning and delivery of radiation therapy now enable more tightly focused administration to minimize the risk. Despite advances, RILD remains a limitation of the use of radiation therapy. Increased awareness and improved implementation of technical and clinical measures that abate the chance of RILD are critical in guiding patient selection and toxicity minimization strategies; however, treatment stratagems are lacking. Although the patients in the report by Samuels et al would likely have been spared the development of RILD, future efforts aimed to identify novel therapeutics for treatment are critical to optimize care for children at risk for RILD development." @default.
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• W3113171624 title "50 Years Ago in T J P" @default.
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