title: Decreased risk of cholangiocarcinogenesis following repeated cycles of Opisthorchis viverrini infection-praziquantel treatment: Magnetic Resonance Imaging (MRI) and histopathological study in a hamster model.
abstract: It has been suggested that repeated infection of Opisthorchis viverrini followed by repeated treatment with praziquantel (PZQ) increases risk of development of cholangiocarcinoma (CCA). Evidence for the prediction has accumulated based on findings of indirect approaches involving molecular changes and epidemiological trends. By contrast, here we directly monitored the impact of repeated liver fluke infection and treatment with PZQ on cholangiocarcinogenesis in a rodent model of human opisthorchiasis, using magnetic resonance imaging (MRI) and histopathology. Twenty five Syrian golden hamsters were assigned to five treatment groups: 1) infection with O. viverrini (OV group), 2) treatment with the carcinogen N-nitrosodimethylamine (NDMA) at 12.5ppm (DMN), 3) O. viverrini infection in tandem with NDMA (OD), 4) O. viverrini infection, NDMA, and treatment with PZQ (ODP), and 5) uninfected, untreated control. The repeated infections were established by intragastric inoculation of 50 metacercariae of O. viverrini to the OV, OD and ODP hamsters at weeks 0, 5 and 10. PZQ at 300mg/kg body weight was given to each hamster of the ODP group on weeks 4, 9 and 13 (four weeks after each infection). Imaging by MRI was undertaken on weeks 5, 10 and 14 (i.e. one week after each PZQ treatment). MRI revealed that the ODP hamsters did not develop CCA, whereas necropsy at week 40 revealed CCA in hamsters of the OD and DMN groups. Findings for histopathology and for proliferating cell nuclear antigen index conformed to the MRI findings. In overview, and notwithstanding that the immune response of individual hosts may play roles in cholangiocarcinogenesis, three cycles of the infection with O. viverrini followed treatment of the infection with PZQ did not increase the risk of bile duct cancer in this hamster model of liver fluke infection-induced CCA.
authors.affiliation: Department of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Petcharakorn
authors.initials: P
authors.lastname: Hanpanich
authors.affiliation: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian liver fluke disease), Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Thewarach
authors.initials: T
authors.lastname: Laha
authors.affiliation: Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian liver fluke disease), Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Banchob
authors.initials: B
authors.lastname: Sripa
authors.affiliation: Department of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian liver fluke disease), Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Eimorn
authors.initials: E
authors.lastname: Mairiang
authors.affiliation: Graduate School, Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Piya
authors.initials: P
authors.lastname: Sereerak
authors.affiliation: Graduate School, Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Songkaid
authors.initials: S
authors.lastname: Upontain
authors.affiliation: Department of Veterinary Anatomy, Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Prasarn
authors.initials: P
authors.lastname: Tangkawattana
authors.affiliation: Department of Microbiology, Immunology & Tropical Medicine, Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, United States.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Brindley
authors.affiliation: Department of Veterinary Pathobiology, Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian liver fluke disease), Khon Kaen University, Khon Kaen 40002, Thailand. Electronic address: sirikach@kku.ac.th.
authors.forename: Sirikachorn
authors.initials: S
authors.lastname: Tangkawattana
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000469:parasitology*; D063646:Carcinogenesis / Q000187:drug effects*; D018281:Cholangiocarcinoma / Q000469:parasitology*; D006224:Cricetinae; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008647:Mesocricetus; D009889:Opisthorchiasis / Q000150:complications / Q000188:drug therapy* / Q000469:parasitology; D009891:Opisthorchis / Q000502:physiology*; D011223:Praziquantel / Q000627:therapeutic use*; D012306:Risk
chemical_list: D000871:Anthelmintics; D011223:Praziquantel
keywords: Cholangiocarcinoma; Hamster; MRI; Opisthorchis; Praziquantel; Repeated infection