title: Administration of bisphosphonates for malignant hepatic tumor with hypercalcemia.
abstract: OBJECTIVE
  Hypercalcemia is a paraneoplastic syndrome that is a serious condition requiring urgent treatment. We administered alendronate to hypercalcemia patients with advanced cancer with metastasized liver tumors or hepatocellular carcinoma (HCC) and then evaluated the mechanism and anticancer function of this compound.
  
  
  METHODS
  We retrospectively studied 17 patients with hypercalcemia associated with metastatic liver tumor or HCC. Alendronate (10mg) was administered via the intravenous route for patients with metastatic liver tumor (n=12) and via the hepatic artery for patients with HCC (n=5).
  
  
  RESULTS
  Intravenous administration of alendronate resulted in decrease in serum calcium levels in all patients. The serum levels of tumor markers also decreased in 66.7% (8/12) of these patients. After intra-arterial alendronate administration, the serum calcium and parathyroid hormone-related protein levels decreased in all the patients. The serum levels of tumor markers such as AFP and PIVKA-II were decreased in 80% (4/5) of these patients. Electron microscopic examination of the resected hepatic tumor revealed an increase in the vascularization and formation of apoptotic vesicles in the vascular endothelial cells.
  
  
  CONCLUSIONS
  Alendronate is effective not only for controlling hypercalcemia but also for directly enhancing the apoptosis of HCC cells.
authors.affiliation: Department of Surgery, Yokohama Central Hospital, Yokohama, Japan. ooida.takatsugu@yokochu.jp
authors.forename: Takatsugu
authors.initials: T
authors.lastname: Oida
authors.forename: Kenji
authors.initials: K
authors.lastname: Mimatsu
authors.forename: Hisao
authors.initials: H
authors.lastname: Kano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawasaki
authors.forename: Youichi
authors.initials: Y
authors.lastname: Kuboi
authors.forename: Nobutada
authors.initials: N
authors.lastname: Fukino
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Kida
authors.forename: Sadao
authors.initials: S
authors.lastname: Amano
mesh_terms: D000368:Aged; D019386:Alendronate / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000097:blood; D002118:Calcium / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000150:complications* / Q000601:surgery / Q000648:ultrastructure; D004164:Diphosphonates / Q000008:administration & dosage*; D005260:Female; D006498:Hepatectomy; D006499:Hepatic Artery; D006801:Humans; D006934:Hypercalcemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008113:Liver Neoplasms / Q000097:blood / Q000150:complications* / Q000556:secondary / Q000601:surgery / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D010257:Paraneoplastic Syndromes / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D012189:Retrospective Studies; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D004164:Diphosphonates; D002118:Calcium; D019386:Alendronate