(LUẬN án TIẾN sĩ) nghiên cứu giá trị của beta hCG tự do và hCG toàn phần huyết thanh trong bệnh nguyên bào nuôi

BỘ GIÁO DỤC VÀ ĐÀO TẠO BỘ Y TẾ TRƯỜNG ĐẠI HỌC Y HÀ NỘI MAI TRỌNG DŨNG NGHIÊN CỨU GIÁ TRỊ CỦA BETA HCG TỰ DO VÀ HCG TOÀN PHẦN HUYẾT THANH TRONG BỆNH NGUYÊN BÀO NUÔI LUẬN ÁN TIẾN SĨ Y HỌC HÀ NỘI - 2022 LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com BỘ GIÁO DỤC VÀ ĐÀO TẠO BỘ Y TẾ TRƯỜNG ĐẠI HỌC Y HÀ NỘI MAI TRỌNG DŨNG NGHIÊN CỨU GIÁ TRỊ CỦA BETA HCG TỰ DO VÀ HCG TOÀN PHẦN HUYẾT THANH TRONG BỆNH NGUYÊN BÀO NUÔI Chuyên ngành : Sản Phụ khoa Mã số : 9720105 LUẬN ÁN TIẾN SĨ Y HỌC Người hướng dẫn khoa học: PGS.TS Phạm Huy Hiền Hào HÀ NỘI - 2022 LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com LỜI CAM ĐOAN Tôi Mai Trọng Dũng, nghiên cứu sinh khóa 35, Trường Đại học Y Hà Nội, chuyên ngành Sản Phụ khoa xin cam đoan: Đây luận án thân trực tiếp thực hướng dẫn Thầy: PGS.TS Phạm Huy Hiền Hào Cơng trình khơng trùng lặp với nghiên cứu khác công bố Việt Nam Các số liệu thông tin nghiên cứu hồn tồn xác, trung thực khách quan, xác nhận chấp thuận sở nơi nghiên cứu Tơi xin hồn toàn chịu trách nhiệm trước pháp luật cam kết Hà Nội, ngày tháng năm 2022 Người viết cam đoan Mai Trọng Dũng LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com DANH MỤC CÁC CHỮ VIẾT TẮT αhCG Alpha Human Chorionic Gonadotropin hCG Beta Human Chorionic Gonadotropin AUC Diện tích đường cong (Area Under the Curve) CDKN1C Cyclin-dependent kinase inhibitor 1C CIA Chemiluminescent Immuno Assay CRP C – reactive protein CT Chửa trứng CTBP Chửa trứng bán phần CTHT Chửa trứng hoàn toàn CTXN Chửa trứng xâm nhập E2 Estradiol ECL Electrode Chemi Luminescence EIA Enzyme immunoassays ELISA Enzyme-linked Immunosorbent assay FIGO International Federation of Gynecology and Obstetrics FRHM Familial Recurrent Hydatidiform Moles FSH Follicle Stimulating Hormone GPH Glycoprotein Hormone Hb Haemoglobin HCG Human Chorionic Gonadotropin HCG-H Human Chorionic Gonadotropin Hyperglycosylated HPL Human Placental Lactogen IA Immunofluorescence assays IPL Imprinted in placenta and liver IS International Standard LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com ISOBM International Society of Oncology and Biomarkers ITA Invasive trophoblast antigen IU International Unit KHDC3L KH Domain Containing Like LH Hormone Luteinizing Max Giá trị lớn Min Giá trị nhỏ mMoM Mean multiple of the median NLRP7 NACHT, LRR and PYD domains-containing protein PIGF Placenta growth factor PLAP Placental alkaline phosphatase RIA Radioimmunoassay ROC Receiver Operating Characteristic sFlt1 Soluble fms-like tyrosine kinase-1 T4 Thyroxine TGFβ Transforming growth factor beta TSH Thyroid-stimulating hormone UNBN U nguyên bào nuôi VEGF Vascular endothelial growth factor WHO World Health Organization ± SD Trung bình ± Độ lệch chuẩn (Mean ± Standard Deviation) LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com MỤC LỤC LỜI CAM ĐOAN DANH MỤC CÁC CHỮ VIẾT TẮT MỤC LỤC DANH MỤC BẢNG DANH MỤC BIỂU ĐỒ DANH MỤC HÌNH ĐẶT VẤN ĐỀ CHƯƠNG 1: TỔNG QUAN TÀI LIỆU 1.1 Tổng quan bệnh nguyên bào nuôi 1.1.1 Phân loại mô bệnh học bệnh nguyên bào nuôi 1.1.2 Tính chất di truyền bệnh nguyên bào nuôi 1.1.3 Chẩn đốn bệnh ngun bào ni 10 1.1.4 Điều trị bệnh nguyên bào nuôi 12 1.1.5 Theo dõi sau điều trị 14 1.2 Đặc điểm cấu trúc chức sinh học hCG 15 1.2.1 Cấu trúc phân tử hCG 16 1.2.2 Chuyển hóa hCG 19 1.3 Chức sinh học hCG thai nghén 20 1.3.1 Chức sinh học phân tử hCG thông thường 21 1.3.2 Chức sinh học hCG-H 22 1.3.3 Chức sinh học βhCG tự 23 1.3.4 Chức sinh học hCG tuyến yên 24 1.4 Các phương pháp xét nghiệm hCG 25 1.4.1 Xét nghiệm hCG phương pháp sinh vật 25 1.4.2 Xét nghiệm hCG phương pháp miễn dịch 25 1.4.3 Tính đặc hiệu ứng dụng phương pháp xét nghiệm 30 1.5 Các vấn đề tồn chẩn đốn tiên lượng bệnh ngun bào ni kết số nghiên cứu liên quan đến βhCG tự do, hCG toàn phần huyết 32 LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com Chương 2: ĐỐI TƯỢNG VÀ PHƯƠNG PHÁP NGHIÊN CỨU 35 2.1 Đối tượng nghiên cứu 35 2.1.1 Tiêu chuẩn lựa chọn 35 2.1.2 Tiêu chuẩn loại trừ 36 2.1.3 Tiêu chuẩn chẩn đoán u nguyên bào nuôi sau chửa trứng 37 2.1.4 Tiêu chuẩn khỏi bệnh theo dõi sau nạo trứng 37 2.2 Phương pháp nghiên cứu 37 2.2.1 Thiết kế nghiên cứu 37 2.2.2 Cỡ mẫu nghiên cứu 37 2.2.3 Phương pháp tiến hành nghiên cứu 39 2.2.4 Thu thập thông tin cho nghiên cứu 42 2.2.5 Xét nghiệm βhCG tự hCG nguyên vẹn huyết 44 2.2.6 Tính nồng độ hCG tồn phần tỷ lệ βhCG tự do/hCG toàn phần huyết 46 2.3 Phương pháp phân tích xử lý số liệu 46 2.4 Vấn đề đạo đức nghiên cứu 47 Chương 3: KẾT QUẢ NGHIÊN CỨU 48 3.1 Một số đặc điểm nhóm nghiên cứu 48 3.1.1 Một số đặc điểm nhóm chửa trứng 48 3.1.2 Đặc điểm nhóm đối chứng 59 3.2 Kết mục tiêu 60 3.2.1 Giá trị loại hCG huyết chửa trứng 61 3.2.2 Giá trị loại hCG huyết chửa thường 62 3.2.3 Giá trị loại hCG huyết u nguyên bào nuôi 62 3.2.4 So sánh giá trị hCG huyết nhóm 63 3.3 Kết mục tiêu 76 CHƯƠNG 4: BÀN LUẬN 79 4.1 Bàn luận số đặc điểm nhóm nghiên cứu 79 4.1.1 Bàn luận số đặc điểm nhóm chửa trứng 79 4.1.2 Đặc điểm nhóm đối chứng 97 4.2 Bàn luận mục tiêu nghiên cứu 98 LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com 4.2.1 Giá trị loại hCG huyết chửa trứng 98 4.2.2 Giá trị loại hCG huyết chửa thường 103 4.2.3 Giá trị loại hCG huyết u nguyên bào ni 105 4.2.4 Bàn luận vai trị βhCG tự do, hCG nguyên vẹn, hCG toàn phần tỷ lệ βhCG tự do/hCG toàn phần huyết chẩn đoán phân biệt chửa trứng, chửa thường, u nguyên bào nuôi 109 4.3 Bàn luận mục tiêu 127 KẾT LUẬN 136 KIẾN NGHỊ 138 CÁC BÀI BÁO CÓ LIÊN QUAN ĐẾN NỘI DUNG LUẬN ÁN TÀI LIỆU THAM KHẢO PHỤ LỤC LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com DANH MỤC BẢNG Bảng 1.1 Bảng 3.1 Bảng 3.2 Bảng 3.3 Bảng 3.4 Bảng 3.5 Bảng 3.6 Bảng 3.7 Bảng 3.8 Bảng 3.9 Bảng 3.10 Bảng 3.11 Bảng 3.12 Bảng 3.13 Bảng 3.14 Bảng 3.15 Bảng 3.16 Bảng 3.17 Bảng 3.18 Bảng 3.19 Bảng 3.20 Bảng 3.21 Bảng 3.22 Bảng 3.23 Bảng 3.24 Bảng 4.1 Chẩn đoán UNBN dựa vào giới hạn tối đa nồng độ βhCG huyết hàng tuần nghiên cứu Phạm Huy Hiền Hào 2004 13 Đặc điểm nhóm tuổi loại chửa trứng 49 Đặc điểm tuổi thai chẩn đoán chửa trứng 50 Một số đặc điểm lâm sàng chẩn đoán chửa trứng 51 Đặc điểm nồng độ Hb với loại chửa trứng 52 Kết βhCG huyết chẩn đoán chửa trứng 53 Phương pháp loại bỏ chửa trứng 54 Tỷ lệ biến chứng u nguyên bào nuôi chửa trứng 54 Một số yếu tố lâm sàng có liên quan đến biến chứng u nguyên bào nuôi 56 Liên quan nồng độ Hb biến chứng u nguyên bào nuôi 57 Liên quan βhCG huyết biến chứng u ngun bào ni 58 Các đặc điểm nhóm thai thường 59 Các đặc điểm nhóm u ngun bào ni đối chứng 59 Nguồn gốc xuất phát phương pháp chẩn đoán u ngun bào ni nhóm đối chứng 60 Giá trị loại hCG huyết chửa trứng 61 Giá trị loại hCG huyết chửa thường 62 Giá trị loại hCG huyết u nguyên bào nuôi 62 So sánh giá trị hCG huyết chửa trứng hoàn toàn chửa trứng bán phần 63 So sánh giá trị trung bình hCG huyết chửa trứng với chửa thường 65 So sánh giá trị trung vị hCG chửa trứng với chửa thường 66 So sánh tỷ lệ βhCG tự do/hCG toàn phần huyết chửa trứng hoàn toàn u nguyên bào nuôi 71 So sánh tỷ lệ βhCG tự do/hCG toàn phần huyết chửa trứng bán phần u nguyên bào nuôi 72 So sánh tỷ lệ βhCG tự do/hCG toàn phần huyết chửa trứng chung u nguyên bào nuôi 73 So sánh tỷ lệ βhCG tự do/hCG toàn phần huyết chửa thường u nguyên bào nuôi 74 Liên quan giá trị hCG với biến chứng u nguyên bào nuôi 76 Giá trị tỷ lệ phần hCG huyết theo nghiên cứu Cole năm 2009 104 LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com DANH MỤC BIỂU ĐỒ Biểu đồ 3.1 Biểu đồ 3.2 Biểu đồ 3.3 Biểu đồ 3.4 Phân loại chửa trứng hoàn toàn bán phần 48 Thời gian nồng độ βhCG âm tính theo loại chửa trứng 55 Thời gian xuất u nguyên bào nuôi 55 Biểu diễn đường cong ROC giá trị hCG huyết chẩn đoán phân biệt chửa trứng hoàn toàn chửa trứng bán phần 64 Biểu đồ 3.5 Biểu diễn đường cong ROC giá trị hCG huyết chẩn đoán phân biệt chửa trứng hoàn toàn chửa thường 67 Biểu đồ 3.6 Biểu diễn đường cong ROC giá trị hCG huyết chẩn đoán phân biệt chửa trứng bán phần chửa thường 68 Biểu đồ 3.7 Biểu diễn đường cong ROC giá trị hCG huyết chửa trứng chung chửa thường 69 Biểu đồ 3.8 Biểu diễn đường cong ROC tỷ lệ βhCG tự do/hCG tồn phần huyết chẩn đốn phân biệt CTHT UNBN 71 Biểu đồ 3.9 Biểu diễn đường cong ROC tỷ lệ βhCG tự do/hCG toàn phần huyết chẩn đoán phân biệt CTBP UNBN 72 Biểu đồ 3.10 Biểu diễn đường cong ROC tỷ lệ βhCG tự do/hCG toàn phần huyết chẩn đoán phân biệt chửa trứng u nguyên bào nuôi 73 Biểu đồ 3.11 Biểu diễn đường cong ROC tỷ lệ βhCG tự do/hCG toàn phần huyết chẩn đoán phân biệt chửa thường u nguyên bào nuôi 75 Biểu đồ 3.12 Biểu diễn đường cong ROC giá trị hCG huyết chửa trứng có biến chứng khơng có biến chứng 77 LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com 59 60 61 62 63 64 65 66 67 68 69 Cole LA Hyperglycosylated hCG Placenta 2007;28(10):977-986 Sturgeon CM, McAllister EJ Analysis of hCG: clinical applications and assay requirements Annals of clinical biochemistry 1998;35(4):460-491 Stenman UH, Tiitinen A, Alfthan H, et al The classification, functions and clinical use of different isoforms of HCG Hum Reprod Update 2006;12(6):769-784 Cole LA Immunoassay of human chorionic gonadotropin, its free subunits, and metabolites Review Clinical chemistry 1997;43(12):2233–2243 Korhonen J, Alfthan H, Ylöstalo P, et al Disappearance of human chorionic gonadotropin and its α- and β-subunits after term pregnancy Clinical chemistry 1997;43(11):2155-2163 Cole LA Antibodies and hCG tests Human Chorionic Gonadotropin (hCG) 2nd ed Massachusetts:Elsevier Publishers; 2015:313-321 Shi QJ, Lei ZM, Rao CV, et al Novel role of human chorionic gonadotropin in differentiation of human cytotrophoblasts Endocrinology 1993;132(3):1387-1395 Cronier L, Bastide B, Herve JC, et al Gap junctional communication during human trophoblast differentiation: influence of human chorionic gonadotropin Endocrinology 1994;135(1):402-408 Cole LA, Shahabi S, Oz UA, et al Hyperglycosylated human chorionic gonadotropin (invasive trophoblast antigen) immunoassay: A new basis for gestational Down syndrome screening Clinical chemistry 1999;45(12):2109-2119 Cole LA, Dai D, Butler SA, et al Gestational trophoblastic diseases: Pathophysiology of hyperglycosylated hCG Gynecol Oncol 2006;102(2):145-150 Handschuh K, Guibourdenche J, Tsatsaris V, et al Human chorionic gonadotropin produced by the invasive trophoblast but not the villous trophoblast promotes cell invasion and is down-regulated by peroxisome proliferator-activated receptor-gamma Endocrinology 2007;148(10):5011-5119 LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com 70 71 72 73 74 75 76 77 78 79 Cole LA Structures of hCG free α-subunit and free β-subunit Human Chorionic Gonadotropin (hCG) 2nd ed Massachusetts:Elsevier Publishers; 2015:51-57 Cole LA New discoveries on the biology and detection of human chorionic gonadotropin Reproductive biology and endocrinology : RB&E 2009;7:8 doi:10.1186/1477-7827-7-8 Cole LA The hCG assay or pregnancy test Clin Chem Lab Med 2012;50(4):617-630 Nguyễn Thế Khánh, Phạm Tử Dương Chẩn đốn có thai Xét nghiệm sử dụng lâm sàng Hà Nội: Nhà xuất Y học; 2001:311-340 Cole LA Assays and Antibodies Human Chorionic Gonadotropin (hCG) 2nd ed Massachusetts:Elsevier Publishers; 2015:311-340 Cole LA Human chorionic gonadotropin tests Expert review of molecular diagnostics 2009;9(7):721-747 Cole LA Problems with today’s hCG pregnancy tests Human Chorionic Gonadotropin (hCG) 2nd ed Massachusetts:Elsevier Publishers; 2015:323-334 Burns C, Moore M, Sturgeon C, et al WHO International Collaborative Study of the proposed 5th International Standard for Chorionic Gonadotrophin WHO/BS/09.2107 Expert committee on biological standardization, Geneva, 19 – 23 October 2009 Available at: https://apps.who.int/iris/handle/10665/70154 Accessed October 2009 Moore M, Partridge K, Cowper B, et al Proposed 6th WHO International Standard for human chorionic gonadotrophin WHO/BS/2020.2395 Expert committee on biological standardization, Geneva, 19 – 23 October 2020 Available at: https://www.who.int/publications/m/item/WHOBS2020.2395 Accessed October 2020 Gnoth C, Johnson S Strips of Hope: Accuracy of Home Pregnancy Tests and New Developments Geburtshilfe und Frauenheilkunde 2014;74(7):661-669 LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com 80 81 82 83 84 85 86 87 88 89 Berger P, Lapthorn AJ Standardization of Epitopes for Human Chorionic Gonadotropin (hCG) Immunoassays Current medicinal chemistry 2016;23(30):3481-3494 Shiefa S, Amargandhi M, Bhupendra J, Moulali S, Kristine T First Trimester Maternal Serum Screening Using Biochemical Markers PAPP-A and Free beta-hCG for Down Syndrome, Patau Syndrome and Edward Syndrome Indian J Clin Biochem 2013;28(1):3-12 Duc HN, van Trommel NE, Sweep FC, et al Clinical utility of hyperglycosylated hCG in serum taken before hydatidiform mole evacuation to predict persistent trophoblastic disease The International journal of biological markers 2006;21(1):45-49 Toriola AT, Tolockiene E, Schock H, et al Free beta-human chorionic gonadotropin, total human chorionic gonadotropin and maternal risk of breast cancer Future Oncol 2014;10(3):377-384 Acevedo HF, Tong JY, Hartsock RJ Human chorionic gonadotropinbeta subunit gene expression in cultured human fetal and cancer cells of different types and origins Cancer 1995;76(8):1467-1475 Bagshawe KD Choriocarcinoma: A model for tumour markers Acta Oncologica 2009;31(1):99-106 Gaspard UJ, Reuter AM, Deville JL, et al Serum concentration of human chorionic gonadotropin and its alpha and beta subunits Trophoblastic tumours Clinical endocrinology 1980;13(4):319-329 Vartiainen J, Alfthan H, Lehtovirta P, et al Elevated hCG and a high proportion of hCGbeta in serum preceding the diagnosis of trophoblastic disease by seven months Bjog 2002;109(5):589-590 Khosravirad A, Zayeri F, Baghestani AR, et al Predictive Power of Human Chorionic Gonadotropin in Post-Molar Gestational Trophoblastic Neoplasia: A Longitudinal Roc Analysis International Journal of Cancer Management 2017;10(9) doi:10.5812/ijcm.9015 Mai Trọng Dũng Nhận xét chẩn đoán chửa trứng Bệnh viện Phụ Sản Trung ương năm 2017 Tạp chí Phụ sản 2018;16(01):127-131 LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com 90 91 92 93 94 95 96 97 98 99 Mai Trọng Dũng Khảo sát giá trị beta hCG tự hCG toàn phần huyết bệnh lý chửa trứng Tạp chí Phụ Sản 2019;16(03):62-67 Mai Trọng Dũng, Phạm Huy Hiền Hào Vai trò loại hCG huyết chẩn đoán phân biệt chửa trứng hồn tồn chửa trứng bán phần Tạp chí Y học Việt Nam 2020;497(1):252-257 Mai Trọng Dũng, Phạm Huy Hiền Hào Vai trò loại hCG huyết tiên lượng biến chứng u nguyên bào nuôi từ chửa trứng Tạp chí Y Dược học 2020;7:116-122 Mai Trọng Dũng, Phạm Huy Hiền Hào Giá trị beta hCG tự huyết chửa trứng, chửa thường u ngun bào ni Tạp chí Nghiên cứu Y học 2021;1:198-206 Mangili G, Giorgione V, Gentile C, et al Hydatidiform mole: agerelated clinical presentation and high rate of severe complications in older women Acta Obstet Gynecol Scand 2014;93(5):503-507 Usui H, Qu J, Sato A, et al Gestational Trophoblastic Neoplasia From Genetically Confirmed Hydatidiform Moles: Prospective Observational Cohort Study Int J Gynecol Cancer 2018;28(9):1772-1780 Cowans NJ, Suonpaa M, Kouru H, et al Evaluation of a dried blood spot assay to measure prenatal screening markers pregnancy-associated plasma protein a and free beta-subunit of human chorionic gonadotropin Clinical chemistry 2013;59(6):968-975 Stenman UH Standardization of assays for human chorionic gonadotropin Clinical chemistry 2004;50(5):798-800 Dương Thị Cương Gestational trophoblastic disease in Vietnam prevalence, clinical features, management Int J Gynaecol Obstet 1998;60(1):131 Nguyễn Quốc Tuấn Nghiên cứu số đặc điểm thường gặp bệnh nhân chửa trứng yếu tố liên quan đến biến chứng Luận án Tiến sĩ Y học Trường Đại học Y Hà Nội, Hà Nội 2003 LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com 100 Nguyễn Văn Thắng Thực trạng bệnh u nguyên bào nuôi Bệnh viện Phụ Sản Trung ương hiệu giải pháp quản lý bệnh nhân cộng đồng Luận án Tiến sĩ Y học Học viện Quân Y, Hà Nội 2020 101 Lelic M, Fatusic Z, Iljazovic E, et al Challenges in the Routine Praxis Diagnosis of Hydatidiform Mole: a Tertiary Health Center Experience Med Arch 2017;71(4):256-260 102 Eagles N, Sebire NJ, Short D, et al Risk of recurrent molar pregnancies following complete and partial hydatidiform moles Human reproduction (Oxford, England) 2015;30(9):2055-2063 103 Soto-Wright V, Bernstein M, Goldstein DP, et al The changing clinical presentation of complete molar pregnancy Obstetrics & Gynecology 1995;86(5):775-779 104 Wolfberg AJ, Berkowitz RS, Goldstein DP, et al Postevacuation hCG levels and risk of gestational trophoblastic neoplasia in women with complete molar pregnancy Obstetrics and gynecology 2005;106(3):548-552 105 Mulisya O, Roberts DJ, Sengupta ES, et al Prevalence and Factors Associated with Hydatidiform Mole among Patients Undergoing Uterine Evacuation at Mbarara Regional Referral Hospital Obstet Gynecol Int 2018;9561413 doi:10.1155/2018/9561413 106 Al-Talib AA Clinical presentation and treatment outcome of molar pregnancy: Ten years experience at a Tertiary Care Hospital in Dammam, Saudi Arabia J Family Community Med 2016;23(3):161-165 107 Joneborg U, Marions L Current Clinical Features of Complete and Partial Hydatidiform Mole in Sweden The Journal of reproductive medicine 2014;59:51-55 108 Garcia M, Romaguera RL, Gomez-Fernandez C A Hydatidiform Mole in a Postmenopausal Woman Archives of Pathology & Laboratory Medicine 2004;128(9):1039-1042 109 El-Agwany AS, Rady HA, Hegab HM Complete Molar Pregnancy in Postmenopausal Woman Indian J Surg Oncol 2017;8(2):185-187 LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com 110 Fisher R, Hodges M, Newlands E Familial recurrent hydatidiform mole: A review The Journal of reproductive medicine 2004;49:595-601 111 Karimi-Zarchi M, Mortazavizadeh MR, Soltani-Gerdefaramrzi M, et al Investigation of Risk Factors, Stage and Outcome in Patients with Gestational Trophoblastic Disease since 2001 to 2011 in Iran-Yazd International journal of biomedical science : IJBS 2015;11(4):166-172 112 Trần Thị Phương Mai Bệnh nguyên bào nuôi thai nghén Bệnh học ung thư Phụ khoa Hà Nội: Nhà xuất Y học; 2005:124-153 113 Lertkhachonsuk A-A Complete hydatidiform mole Change in profile over three decades The Journal of reproductive medicine 2012;57:470-474 114 Sun SY, Melamed A, Joseph NT, et al Clinical Presentation of Complete Hydatidiform Mole and Partial Hydatidiform Mole at a Regional Trophoblastic Disease Center in the United States Over the Past Decades Int J Gynecol Cancer 2016;26(2):367-370 115 Mangili G, Garavaglia E, Cavoretto P, et al Clinical presentation of hydatidiform mole in northern Italy: has it changed in the last 20 years? Am J Obstet Gynecol 2008;198(3):302 e1-302e4 doi:10.1016/j.ajog.2007.09.036 116 Igwegbe A, Eleje G Hydatidiform mole: A Review of Management Outcomes in a Tertiary Hospital in South-East Nigeria Ann Med Health Sci Res 2013;3(2):210-214 117 Zhao P, Chen Q, Lu W Comparison of different therapeutic strategies for complete hydatidiform mole in women at least 40 years old: a retrospective cohort study BMC Cancer 2017;17(1):733 doi:10.1186/s12885-017-3749-8 118 Ocheke AN, Musa J, Uamai AO Hydatidiform mole in Jos, Nigeria Nigerian Medical Journal 2011;52(4):223-226 119 WHO Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity Vitamin and Mineral Nutrition Information System World Health Organization website; 2011 Available at: https://www.who.int/vmnis/indicators/haemoglobin/en/ Accessed 2011 LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com 120 121 122 123 124 125 126 127 128 129 Feltmate CM, Batorfi J, Fulop V, et al Human chorionic gonadotropin follow-up in patients with molar pregnancy: a time for reevaluation Obstetrics & Gynecology 2003;101(4):732-736 Seckin KD, Baser E, Yeral I, et al The impact of ultrasonographic lesion size and initial human chorionic gonadotropin values on treatment success in cases with complete hydatidiform mole European review for medical and pharmacological sciences 2013;17(24):3381-3384 Cavaliere A, Ermito S, Dinatale A, et al Management of molar pregnancy Journal of prenatal medicine 2009;3(1):15-17 Soper JT, Mutch DG, Schink JC, American College of O, Gynecologists Diagnosis and treatment of gestational trophoblastic disease: ACOG Practice Bulletin No 53 Gynecol Oncol 2004;93(3):575-585 Cole LA hCG, the wonder of today's science Reproductive biology and endocrinology : RB&E 2012;10:24 doi:10.1186/1477-7827-10-24 Giorgione V, Bergamini A, Cioffi R, et al Role of Surgery in the Management of Hydatidiform Mole in Elderly Patients: A SingleCenter Clinical Experience Int J Gynecol Cancer 2017;27(3):550-553 Ilancheran A, Ratnam SS The role of surgery in the treatment of trophoblastic disease International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 1980;18(4):237-239 Soma H, Takayama M, Saito T, Isaka K Management of Hydatidiform Mole in Women over 45 Years Old* Asia-Oceania Journal of Obstetrics and Gynaecology 1983;9(4):393-398 Bahar AM, el-Ashnehi MS, Senthilselvan A Hydatidiform mole in the elderly: hysterectomy or evacuation? Int J Gynaecol Obstet Jul 1989;29(3):233-238 Zhao P, Lu Y, Huang W, et al Total hysterectomy versus uterine evacuation for preventing post-molar gestational trophoblastic neoplasia in patients who are at least 40 years old: a systematic review and meta-analysis BMC Cancer 2019;19(1):13 doi:10.1186/s12885018-5168-x LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com 130 Pisal N, North C, Tidy J, Hancock B Role of hysterectomy in management of gestational trophoblastic disease Gynecol Oncol 2002;87(2):190-192 131 Doll KM, Soper JT The role of surgery in the management of gestational trophoblastic neoplasia Obstetrical & gynecological survey 2013;68(7):533-542 132 Brown J, Naumann RW, Seckl MJ, Schink J 15years of progress in gestational trophoblastic disease: Scoring, standardization, and salvage Gynecol Oncol 2017;144(1):200-207 133 Berkowitz RS, Goldstein DP, Horowitz NS Presentation and management of molar pregnancy Gestational Trophoblastic Disease 4th edition ISSTD website; 2015 Available at: https://isstd.org/membership-isstd-2020/gtd-book Accessed September, 2015 134 Eysbouts Y, Brouwer R, Ottevanger P, et al Serum Human Chorionic Gonadotropin Normogram for the Detection of Gestational Trophoblastic Neoplasia Int J Gynecol Cancer Jun 2017;27(5):1035-1041 135 Braga A, Maesta I, Matos M, Elias KM, Rizzo J, Viggiano MG Gestational trophoblastic neoplasia after spontaneous human chorionic gonadotropin normalization following molar pregnancy evacuation Gynecol Oncol 2015;139(2):283-287 136 Coyle C, Short D, Jackson L, et al What is the optimal duration of human chorionic gonadotrophin surveillance following evacuation of a molar pregnancy? A retrospective analysis on over 20,000 consecutive patients Gynecol Oncol 2018;148(2):254-257 137 Wolfberg AJ, Growdon WB, Feltmate CM, et al Low risk of relapse after achieving undetectable HCG levels in women with partial molar pregnancy Obstetrics and gynecology Aug 2006;108(2):393-396 138 Bakhtiyari M, Mirzamoradi M, Kimyaiee P, et al Postmolar gestational trophoblastic neoplasia: beyond the traditional risk factors Fertil Steril 2015;104(3):649-654 LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com 139 Schmitt C, Doret M, Massardier J, et al Risk of gestational trophoblastic neoplasia after hCG normalisation according to hydatidiform mole type Gynecol Oncol 2013;130(1):86-89 140 Smith HO, Hilgers RD, Bedrick EJ, et al Ethnic differences at risk for gestational trophoblastic disease in New Mexico: A 25-year populationbased study Am J Obstet Gynecol 2003;188(2):357-366 141 Bracken MB, Brinton LA, Hayashi K Epidemiology of hydatidiform mole and choriocarcinoma Epidemiologic reviews 1984;6:52-75 142 Lurain JR Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole Am J Obstet Gynecol 2010;203(6):531-539 143 Pradjatmo H, Dasuki D, Dwianingsih EK, et al Malignancy risk scoring of hydatidiform moles Asian Pac J Cancer Prev 2015;16(6):2441-2445 144 Garner EI, Goldstein DP, Feltmate CM, et al Gestational trophoblastic disease Clinical obstetrics and gynecology 2007;50(1):112-122 145 Kim S, Kang W, Choi H The role of hCG ratio in weeks after evacuation of complete mole for predictor of persistent gestational trophoblastic neoplasia Gynecologic Oncology 2012;125:S26 doi:10.1016/j.ygyno.2011.12.044 146 Montz FJ, Schlaerth JB, Morrow CP The natural history of theca lutein cysts Obstetrics and gynecology 1988;72(2):247-251 147 Zhang L, Xie Y, Zhan L The potential value of red blood cell distribution width in patients with invasive hydatidiform mole J Clin Lab Anal 2019;33(4):e22846 doi:10.1002/jcla.22846 148 Kim BW, Cho H, Kim H, et al Human chorionic gonadotrophin regression rate as a predictive factor of postmolar gestational trophoblastic neoplasm in high-risk hydatidiform mole: a case-control study Eur J Obstet Gynecol Reprod Biol 2012;160(1):100-105 LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com 149 Wolfberg AJ, Feltmate C, Goldstein DP,et al Low risk of relapse after achieving undetectable HCG levels in women with complete molar pregnancy Obstetrics and gynecology 2004;104(3):551-554 150 Vree M, van Trommel N, Kenter G, et al The influence of lung metastases on the clinical course of gestational trophoblastic neoplasia: a historical cohort study BJOG 2016;123(11):1839-1845 151 Khazaeli MB, Buchina ES, Pattillo RA, et al Radioimmunoassay of free ß-subunit of human chorionic gonadotropin in diagnosis of highrisk and low-risk gestational trophoblastic disease American Journal of Obstetrics and Gynecology 1989;160(2):444-449 152 Fan C, Goto S, Furuhashi Y, Tomoda Y Radioimmunoassay of the serum free beta-subunit of human chorionic gonadotropin in trophoblastic disease J Clin Endocrinol Metab 1987;64(2):313-318 153 Cole LA Positive hCG tests Human Chorionic Gonadotropin (hCG) 2nd ed Massachusetts:Elsevier Publishers; 2015:291-309 154 Harvey RA, Pursglove HD, Schmid P, et al Human chorionic gonadotropin free beta-subunit measurement as a marker of placental site trophoblastic tumors The Journal of reproductive medicine 2008;53(8):643-648 155 Tang YP, Wu YS, Yin AH, et al Determination of median levels of the free beta subunit of human chorionic gonadotropin in women from Mainland China using a new time-resolved fluoroimmunoassay Clin Chem Lab Med 2010;48(1):109-114 156 Montagnana M, Trenti T, Aloe R, et al Human chorionic gonadotropin in pregnancy diagnostics Clin Chim Acta 2011;412(17-18):1515-1520 157 Cole LA, Khanlian SA, Muller CY, et al Gestational trophoblastic diseases: Human chorionic gonadotropin-free beta-subunit, a reliable marker of placental site trophoblastic tumors Gynecol Oncol 2006;102(2):160-164 LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com 158 Fowler DJ, Lindsay I, Seckl MJ, et al Routine pre-evacuation ultrasound diagnosis of hydatidiform mole: experience of more than 1000 cases from a regional referral center Ultrasound Obstet Gynecol 2006;27(1):56-60 159 Sebire NJ, Rees H, Paradinas F, et al The diagnostic implications of routine ultrasound examination in histologically confirmed early molar pregnancies Ultrasound Obstet Gynecol 2001;18(6):662-665 160 Kimiaee P, Ashrafi-vand S, Mansournia MA, et al Predictive values of different forms of human chorionic gonadotropin in postmolar gestational trophoblastic neoplasia Int J Gynecol Cancer 2014;24(9):1715-1722 161 Vetter V Management of gestational trophoblastic disease JAAPA : official journal of the American Academy of Physician Assistants 2013;26(3):31-35 162 Lybol C, Sweep FC, Ottevanger PB, et al Linear regression of postevacuation serum human chorionic gonadotropin concentrations predicts postmolar gestational trophoblastic neoplasia Int J Gynecol Cancer 2013;23(6):1150-1156 163 Hotakainen K, Ljungberg B, Paju A, et al The free beta-subunit of human chorionic gonadotropin as a prognostic factor in renal cell carcinoma British journal of cancer 2002;86(2):185-189 164 Li J, Yin M, Song W, et al B Subunit of Human Chorionic Gonadotropin Promotes Tumor Invasion and Predicts Poor Prognosis of Early-Stage Colorectal Cancer Cell Physiol Biochem 2018;45(1):237-249 165 Lempiainen A, Stenman UH, Blomqvist C, et al Free beta-subunit of human chorionic gonadotropin in serum is a diagnostically sensitive marker of seminomatous testicular cancer Clinical chemistry 2008;54(11):1840-1843 LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com 166 Froeling FEM, Ramaswami R, Papanastasopoulos P, et al Intensified therapies improve survival and identification of novel prognostic factors for placental-site and epithelioid trophoblastic tumours British journal of cancer Feb 22 2019;doi:10.1038/s41416-019-0402-0 167 Khazaeli MB, Hedayat MM, Hatch KD, et al Radioimmunoassay of free beta-subunit of human chorionic gonadotropin as a prognostic test for persistent trophoblastic disease in molar pregnancy Am J Obstet Gynecol 1986;155(2):320-324 LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com Phụ lục PHỤ LỤC 1.Chuyển đổi đơn vị kết βhCG tự do, hCG nguyên vẹn huyết chửa trứng (n = 191) Giá trị βhCG tự huyết Loại hCG X ± SD (Min - Max) Trung vị (Tứ phân vị) βhCG tự (ng/ml) βhCG tự (nmol/l) βhCG tự (ng/ml) βhCG tự (nmol/l) 529,4 ± 472,3 22,6 ± 20,1 362 15,4 (21,1 – 1991,1) (0,9 – 84,8) (55,9 – 1758,3) (2,4 – 74,9) CTBP 174,0 ± 183,4 (2,6 – 918) 7,4 ± 7,8 (0,1 – 39,1) 122,1 (12,1 – 678,7) 5,2 (0,5 – 28,9) Chửa trứng chung 432,6 ± 443,0 (2,6 – 1991,1) 18,4 ± 18,9 (0,1 – 84,8) 294,1 (24,6 – 1580,6) 12,5 (1,0 – 67,3) Loại chửa trứng CTHT Giá trị hCG nguyên vẹn huyết Loại hCG X ± SD Trung vị (Min - Max) (Tứ phân vị) Loại chửa trứng HCG nguyên vẹn (IU/L) CTHT 260.974 ± 241.073 (13.526 - 1.430.298) 750,1 ± 692,9 175.209 (38,9 - 4110,8) (34.553 – 774.627) 503,6 (99,3 – 2226,3) CTBP 127.543 ± 116.910 (1392 - 92.589) 366,6 ± 336,0 (4,0 - 1703,1) 107.492 (11.760 – 435.516) 308,9 (33,8 – 1251,7) Chửa trứng chung 224.647 ± 222.319 (1392 - 1.430.298) 645,7 ± 639,0 (4,0 - 4110,8) 148.239 (19.384 – 709.213) 426,0 (55,7 – 2038,3) HCG nguyên vẹn (nmol/l) HCG nguyên vẹn (IU/L) HCG nguyên vẹn (nmol/l) LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com Phụ lục PHỤ LỤC Chuyển đổi đơn vị kết βhCG tự do, hCG nguyên vẹn huyết nhóm đối chứng 2.1 Giá trị hCG huyết chửa thường (n=86) Giá trị βhCG tự huyết X ± SD Trung vị (Min – Max) (Tứ phân vị) βhCG tự (ng/ml) 71,2 ± 47,6 (8,7 - 270,6) βhCG tự βhCG tự βhCG tự (nmol/l) (ng/ml) (nmol/l) 3,0 ± 2,0 58,0 2,5 (0,4 – 11,5) (23,0 – 183,4) (1,0 – 7,8) Giá trị hCG nguyên vẹn huyết X ± SD Trung vị (Min - Max) (Tứ phân vị) HCG nguyên vẹn HCG nguyên vẹn HCG nguyên vẹn HCG nguyên vẹn (IU/L) (nmol/l) (IU/L) (nmol/l) 103.930 ± 46.601 298,7 ± 133,9 97.644 280,6 (20.404 - 259.960) (58,6 – 747,1) (41.354 - 202.917) (118,9 – 583,2) 2.2 Giá trị βhCG tự huyết nhóm u ngun bào ni (n=33) Giá trị βhCG tự huyết X ± SD (Min - Max) Trung vị (Tứ phân vị) βhCG tự (ng/ml) 121,7 ± 154,7 (0,14 – 508,0) βhCG tự βhCG tự βhCG tự (nmol/l) (ng/ml) (nmol/l) 5,2 ± 6,6 53,1 2,3 (0,01 – 21,6) (0,2 – 494,0) (0,01 – 21,04) Giá trị hCG nguyên vẹn huyết X ± SD Trung vị (Min - Max) (Tứ phân vị) HCG nguyên vẹn HCG nguyên vẹn HCG nguyên vẹn HCG nguyên vẹn (IU/L) (nmol/l) (IU/L) (nmol/l) 47.403 ± 89.489 (10,6 – 390.030) 136,2 ± 257,2 (0,03 – 1121,0) 8.328 (65 – 321.122) 23,9 (0,2 – 922,9) LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com Savage PM, Sita-Lumsden Dickson S, et al The relationship of maternal age to molar pregnancy incidence, risks for chemotherapy and subsequent pregnancy outcome JA, Obstet Gynaecol May 2013;33(4):406-11 doi:10.3109/01443615.2013.771159 Hào PHH trò beta hCG huyết theo dõi sauTD-7 nạo trứng, điều trị uYVai nguyên bào nuôi số yếu tố liên quan đến tái phát Luận án Tiến sĩsecond học 2004:Trường Đại học Yfor Hà Nội Berger P, Paus E, Hemken PM, et al Candidate epitopes for measurement of hCG and molecules: the second ISOBM workshop Tumour biology :related the journal of the International Society Oncodevelopmental Biology and Medicine Dec 2013;34(6):4033-57 doi:10.1007/s13277-013-0994-6 Benn PA Advances in prenatal screening Down syndrome: I general principles and trimester testing Clin Chim Acta Sep 2002;323(1-2):116 doi:10.1016/s0009-8981(02)00186-9 van Trommel NE, Sweep FC, Schijf CP, Massuger LF, Thomas CM Diagnosis of hydatidiform mole and persistent trophoblastic disease: diagnostic accuracy ofchorionic total chorionic gonadotropin (hCG), free hCG {alpha}and {beta}-subunits, and their ratios J and Endocrinol Oct 2005;153(4):565-75 Ozturk M, Berkowitz R,human Goldstein D, Bellet D, Wands JR.inGynecology Differential production of human gonadotropin and free subunits gestational trophoblastic disease American Journal of Obstetrics 1988/01/01/ 1988;158(1):193-198 doi:https://doi.org/10.1016/00029378(88)90809-5 BERKOWITZ R,doi:10.1530/eje.1.01997 OZTURK M, GOLDSTEIN D,Eur BERNSTEIN M,Serum HILL L, WANDS JR Human Chorionic Gonadotropin and FreeDecember Subunits' Levels in Patients With Partial and Complete Hydatidiform Moles Obstetrics & Gynecology 1989;74(2):212-216 Tempfer C, Horn LC, Ackermann S, et al Gestational and Nongestational Trophoblastic Disease Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry No 032/049, 2015) Geburtshilfe und Frauenheilkunde Feb 2016;76(2):134-144 doi:10.1055/s0041-111788 Genest DR, Laborde O, Berkowitz RS, Goldstein DP, Bernstein MR, Lage J A clinicopathologic study ofby 153 cases complete hydatidiform mole (1980-1990): histologic grade lacks prognostic significance Obstetrics and gynecology Sep 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exaggerated form of “syncytial endometritis” simulating malignant tumor Cancer 1976;38(3):1214-1226 doi:doi:10.1002/10970142(197609)38:33.0.CO;2-J 16 Stevens FT, Katzorke N, C, et al Gestational Trophoblastic Disorders: An Update inY 2015 Geburtshilfe Frauenheilkunde Octa 2015;75(10):1043-1050 doi:10.1055/s-0035-1558054 17 Hamazaki S, Nakamoto S,Tempfer Okino T, et Curtin al.und Epithelioid trophoblastic tumor: morphological and immunohistochemical study of three lung lesions Human pathology Nov 1999;30(11):1321-7 18 Fisher RA, Povey S, Jeffreys AJ, Martin CA, Patel I, Lawler SD Frequency of heterozygous complete hydatidiform moles, estimated by locusspecific minisatellite and chromosome-specific probes Human genetics Jun 1989;82(3):259-63 19 Kovacs BW, Shahbahrami B, Tast DE, JP Molecular genetic analysis of complete hydatidiform moles Cancer genetics andas cytogenetics Jul 15 1991;54(2):143-52 20 Golubovsky MD Postzygotic diploidization of triploids a Obstetrics source of unusual cases of mosaicism, chimerism and twinning Human Reproduction 2003;18(2):236-242 doi:10.1093/humrep/deg060 21 Szulman AE, Surti U The1978/07/15/ syndromes of hydatidiform mole:AE I Cytogenetic and morphologic correlations American Journal of and Gynecology 1978;131(6):665-671 doi:https://doi.org/10.1016/0002-9378(78)90829-3 22 Jacobs PA, Hunt PA, MatsuuraA JS, WILSON CC, SZULMAN Complete and partial hydatidiform mole in Hawaii: cytogenetics, morphology and epidemiology BJOG: An International Journal of Obstetrics & Gynaecology 1982;89(4):258-266 doi:doi:10.1111/j.14710528.1982.tb04693.x 23 Zaragoza MV, Surti U, Redline RW, Millie E, Chakravarti A, Hassold TJ Parental origin and phenotype of triploidy in spontaneous abortions: predominance of diandry and association with the partial hydatidiform mole Am J Hum Genet Jun 2000;66(6):1807-20 doi:10.1086/302951 24 Joergensen MW, Niemann I, Rasmussen AA, et al Triploid pregnancies: genetic and clinical features of 158 cases Am J Obstet 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reproduction and genetics Oct 1996;13(9):739-44 29 Zhang P, McGinniss MJ, Sawai S, Benirschke K Diploid/triploid mosaic placenta with fetus Towards A better understanding of 'partial moles' human development Nov 2000;60(1):1-11 30 Castrillon DH, Sun D, Weremowicz S, Fisher RA, Crum CP, Genest DR Discrimination of complete hydatidiform mole from its mimics by immunohistochemistry of the paternally imprinted gene product p57KIP2 The American journal of surgical OctSeckl 2001;25(10):1225-30 31 Saxena A, Frank D, Panichkul P, Kaur Van den Veyver IB, Tycko B,Sep-Oct Thaker H The product of the imprinted gene IPL marks human villous cytotrophoblast and isL, lost infrom complete mole Placenta 2003;24(8-9):835-42 32 Fisher RA, Tommasi A, Short D, B, MJ, Sebire NJ Clinical utility selective molecular genotyping for diagnosis of partial hydatidiform mole; aofNov retrospective study apathology regional trophoblastic disease unit J Clin Pathol 2014;67(11):980-4 doi:10.1136/jclinpath-2014-202517 33 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beta-subunit of human chorionic gonadotropin asBritish aprognostic prognostic test for persistent trophoblastic disease inHatch molar pregnancy Am J etObstet Aug 1986;155(2):320-4 TÀI LIỆU THAM KHẢO ENDNOTE (KHÔNG IN) LUAN VAN CHAT LUONG download : add luanvanchat@agmail.com ... nguyên vẹn, hCG toàn phần tỷ lệ ? ?hCG tự do /hCG toàn phần huyết bệnh nguyên bào nuôi, chửa thường Xác định giá trị ? ?hCG tự do, hCG nguyên vẹn, hCG toàn phần tỷ lệ ? ?hCG tự do /hCG toàn phần huyết tiên... bán phần u nguyên bào nuôi 72 So sánh tỷ lệ ? ?hCG tự do /hCG toàn phần huyết chửa trứng chung u nguyên bào nuôi 73 So sánh tỷ lệ ? ?hCG tự do /hCG toàn phần huyết chửa thường u nguyên bào. .. ? ?hCG tự hCG ngun vẹn sau tính tốn giá trị hCG tồn phần tỷ lệ ? ?hCG tự do /hCG tồn phần huyết Mục tiêu nhóm nghiên cứu là: - Xác định trị số ? ?hCG tự do, hCG nguyên vẹn, hCG toàn phần tỷ lệ ? ?hCG tự