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Wang MD, Wang BD, Diao YK, Li C, Yao LQ, Liu H, Zeng YY, Chen Z, Wu H, Xu XF, Gu LH, Xu JH, Yin DX, Li YC, Chen FJ, Kow AWC, Pawlik TM, Shen F, Yang T. Tumour Biology Characteristics Score Based on AFP and PIVKA-II Predicts Recurrence and Survival After Curative Resection for Hepatocellular Carcinoma: A Multicentre Cohort Study. J Gastrointest Surg 2025:102038. [PMID: 40157713 DOI: 10.1016/j.gassur.2025.102038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2025] [Revised: 03/03/2025] [Accepted: 03/22/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND Current hepatocellular carcinoma (HCC) staging systems lack comprehensive assessment of tumour biological characteristics. This study aimed to develop and validate a tumour biology characteristics score (TBCS) based on alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) to predict long-term oncologic outcomes after HCC resection. METHODS In this multicentre retrospective cohort study, patients who underwent curative resection for HCC between June 2018 and December 2022 were included. TBCS (range 2-6 points) was calculated by combining preoperative AFP (<20, 20~199, ≥200ng/mL) and PIVKA-II (<40, 40~399, ≥400 mAU/mL) levels. Patients were stratified into low (2 points), medium (3~4 points), and high (5~6 points) TBCS groups. The primary outcomes were recurrence-free survival (RFS) and overall survival (OS). RESULTS A total of 695 patients were analysed; the low, medium, and high TBCS groups comprised 132 (19.0%), 233 (33.5%), and 330 (47.5%) patients, respectively. 5-year RFS was 30.4%, 14.7%, and 9.7%, while 5-year OS was 42.1%, 35.5%, and 23.5% for low, medium, and high TBCS groups, respectively (both P<0.001). Multivariate analysis identified TBCS as an independent predictor of both RFS (medium TBCS: HR 1.583, 95% CI 1.219-2.057, P=0.001; high TBCS: HR 1.895, 95% CI 1.473-2.438, P<0.001) and OS (high TBCS: HR 1.781, 95% CI 1.353-2.343, P<0.001). CONCLUSIONS The novel TBCS combining AFP and PIVKA-II effectively stratified HCC patients into distinct prognostic groups after curative-intent resection, independently predicting both RFS and OS. This score may help identify high-risk patients for more intense postoperative recurrence surveillance, as well as receipt of adjuvant therapies.
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Affiliation(s)
- Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Bai-Dong Wang
- Second Military Medical University (Naval Medical University), Shanghai, China
| | - Yong-Kang Diao
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Lan-Qing Yao
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Han Liu
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Centre, First Hospital of Jilin University, Changchun, Jilin, China
| | - Yong-Yi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fujian, China
| | - Zhong Chen
- Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Han Wu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Xin-Fei Xu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Li-Hui Gu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Jia-Hao Xu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Dong-Xu Yin
- School of Public Health, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Yu-Chen Li
- Department of Graduate, Bengbu Medical University, Bengbu, Anhui, China
| | - Fu-Jie Chen
- Department of Graduate, Bengbu Medical University, Bengbu, Anhui, China
| | - Alfred Wei Chieh Kow
- Division of Hepatopancreaticobiliary Surgery and Liver Transplantation, Department of Surgery, National University Health System Singapore, Singapore
| | - Timothy M Pawlik
- Department of Surgery, Ohio State University, Wexner Medical Centre, Columbus, OH, United States
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China; Eastern Hepatobiliary Clinical Research Institute, Third Affiliated Hospital of Naval Medical University, Shanghai, China.
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China; School of Public Health, Hangzhou Medical College, Hangzhou, Zhejiang, China; Department of Graduate, Bengbu Medical University, Bengbu, Anhui, China; Eastern Hepatobiliary Clinical Research Institute, Third Affiliated Hospital of Naval Medical University, Shanghai, China.
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Nakagawa S, Hayashi H, Itoyama R, Kitano Y, Mima K, Okabe H, Baba H. BALAD score predicts the recurrence and survival in the patients who underwent initial hepatectomy for HCC. Surg Oncol 2024; 55:102097. [PMID: 39029425 DOI: 10.1016/j.suronc.2024.102097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 06/03/2024] [Accepted: 06/28/2024] [Indexed: 07/21/2024]
Abstract
BACKGROUNDS Several studies have indicated that BALAD score which includes the HCC tumor markers of HCC, AFP, AFP-L3%, DCP, and serum albumin and bilirubin value were good predictors of HCC patients for all treatment modalities. In this study, we aim to clarify the impact of BALAD score as the prognostic factor for HCC patients after curative surgery. METHODS This study investigated 578 patients who underwent hepatectomy for HCC between January 2003 and May 2013. Cumulative recurrence rate, overall survival (OS), and clinicopathological parameters were analyzed according to the level of BALAD score. RESULTS In patients with higher BALAD score, recurrence rate and OS was poor (p = 0.0015 and p < 0.0001, respectively). Multivariate analyses revealed independent risk factors for recurrence to be male (hazard ratio [HR] 1.52, P = 0.011), HCV-antibody positive (HR 1.33, P = 0.019), multiple tumors (HR 2.16, P < 0.0001), microvascular invasion (HR 1.45, P = 0.0035) and higher BALAD score (RR 1.70, P = 0.015). The independent risk factors for OS were multiple tumors (HR 1.52, P = 0.014), microvascular invasion (HR 1.53, P = 0.012), and higher BALAD score (RR 2.51, P = 0.0012). CONCLUSION BALAD score is associated with high recurrence rate and poor overall survival of the patients who underwent curative liver resection for HCC.
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Affiliation(s)
- Shigeki Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-0811, Japan.
| | - Hiromitsu Hayashi
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-0811, Japan
| | - Rumi Itoyama
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-0811, Japan
| | - Yuki Kitano
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-0811, Japan
| | - Kosuke Mima
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-0811, Japan
| | - Hirohisa Okabe
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-0811, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-0811, Japan
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Kato H, Hayami S, Ueno M, Suzaki N, Nakamura M, Yoshimura T, Miyamoto A, Shigekawa Y, Okada K, Miyazawa M, Kitahata Y, Ehata S, Hamamoto R, Yamaue H, Kawai M. Histone methyltransferase SUV420H1/KMT5B contributes to poor prognosis in hepatocellular carcinoma. Cancer Sci 2024; 115:385-400. [PMID: 38082550 PMCID: PMC10859612 DOI: 10.1111/cas.16038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 10/15/2023] [Accepted: 11/20/2023] [Indexed: 02/13/2024] Open
Abstract
Hepatocellular carcinoma (HCC) has a high rate of recurrence and poor prognosis, even after curative surgery. Multikinase inhibitors have been applied for HCC patients, but their effect has been restricted. This study aims to clarify the clinical impact of SUV420H1/KMT5B, one of the methyltransferases for histone H4 at lysine 20, and elucidate the novel mechanisms of HCC progression. We retrospectively investigated SUV420H1 expression using HCC clinical tissue samples employing immunohistochemical analysis (n = 350). We then performed loss-of-function analysis of SUV420H1 with cell cycle analysis, migration assay, invasion assay and RNA sequence for Gene Ontology (GO) pathway analysis in vitro, and animal experiments with xenograft mice in vivo. The SUV420H1-high-score group (n = 154) had significantly poorer prognosis for both 5-year overall and 2-year/5-year disease-free survival than the SUV420H1-low-score group (n = 196) (p < 0.001 and p < 0.05, respectively). The SUV420H1-high-score group had pathologically larger tumor size, more tumors, poorer differentiation, and more positive vascular invasion than the SUV420H1-low-score group. Multivariate analysis demonstrated that SUV420H1 high score was the poorest independent factor for overall survival. SUV420H1 knockdown could suppress cell cycle from G1 to S phase and cell invasion. GO pathway analysis showed that SUV420H1 contributed to cell proliferation, cell invasion, and/or metastasis. Overexpression of SUV420H1 clinically contributed to poor prognosis in HCC, and the inhibition of SUV420H1 could repress tumor progression and invasion both in vitro and in vivo; thus, further analyses of SUV420H1 are necessary for the discovery of future molecularly targeted drugs.
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Affiliation(s)
- Hirotaka Kato
- Second Department of Surgery, School of MedicineWakayama Medical UniversityWakayamaJapan
| | - Shinya Hayami
- Second Department of Surgery, School of MedicineWakayama Medical UniversityWakayamaJapan
| | - Masaki Ueno
- Second Department of Surgery, School of MedicineWakayama Medical UniversityWakayamaJapan
| | - Norihiko Suzaki
- Second Department of Surgery, School of MedicineWakayama Medical UniversityWakayamaJapan
| | - Masashi Nakamura
- Second Department of Surgery, School of MedicineWakayama Medical UniversityWakayamaJapan
| | - Tomohiro Yoshimura
- Second Department of Surgery, School of MedicineWakayama Medical UniversityWakayamaJapan
| | - Atsushi Miyamoto
- Second Department of Surgery, School of MedicineWakayama Medical UniversityWakayamaJapan
| | - Yoshinobu Shigekawa
- Second Department of Surgery, School of MedicineWakayama Medical UniversityWakayamaJapan
| | - Ken‐Ichi Okada
- Second Department of Surgery, School of MedicineWakayama Medical UniversityWakayamaJapan
| | - Motoki Miyazawa
- Second Department of Surgery, School of MedicineWakayama Medical UniversityWakayamaJapan
| | - Yuji Kitahata
- Second Department of Surgery, School of MedicineWakayama Medical UniversityWakayamaJapan
| | - Shogo Ehata
- Department of Pathology, School of MedicineWakayama Medical UniversityWakayamaJapan
| | - Ryuji Hamamoto
- Division of Medical AI Research and DevelopmentNational Cancer Center Research InstituteTokyoJapan
| | - Hiroki Yamaue
- Second Department of Surgery, School of MedicineWakayama Medical UniversityWakayamaJapan
| | - Manabu Kawai
- Second Department of Surgery, School of MedicineWakayama Medical UniversityWakayamaJapan
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Zhou Z, Liu J, Xu X. A commentary on 'Prothrombin induced by vitamin K Absence-II versus alpha-fetoprotein in detection of both resectable hepatocellular carcinoma and early recurrence after curative liver resection: a retrospective cohort study' ( Int J Surg 2022;105:106843). Int J Surg 2023; 109:3656-3658. [PMID: 36906781 PMCID: PMC10651297 DOI: 10.1097/js9.0000000000000119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 11/10/2022] [Indexed: 03/13/2023]
Affiliation(s)
- Zheyu Zhou
- Department of General Surgery, Nanjing Drum Tower Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Graduate School of Peking Union Medical College
| | - Jinsong Liu
- School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine
| | - Xiaoliang Xu
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
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Tanaka K, Tsuji K, Hiraoka A, Tada T, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Ishikawa T, Tajiri K, Ochi H, Toyoda H, Ogawa C, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Naganuma A, Kosaka H, Matono T, Kuroda H, Yata Y, Ohama H, Tada F, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Yokohama K, Nishikawa H, Imai M, Koizumi Y, Nakamura S, Iijima H, Kaibori M, Hiasa Y, Kumada T. Usefulness of Tumor Marker Score for Predicting the Prognosis of Hepatocellular Carcinoma Patients Treated with Atezolizumab Plus Bevacizumab: A Multicenter Retrospective Study. Cancers (Basel) 2023; 15:4348. [PMID: 37686624 PMCID: PMC10486534 DOI: 10.3390/cancers15174348] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Accepted: 08/28/2023] [Indexed: 09/10/2023] Open
Abstract
AIM This study aimed to evaluate the ability of a previously reported tumor marker (TM) score involving alpha-fetoprotein (AFP), fucosylated AFP (AFP-L3), and des gamma-carboxy prothrombin (DCP) as TMs in predicting the prognosis and therapeutic efficacy in hepatocellular carcinoma (HCC) patients administered atezolizumab plus bevacizumab (Atez/Bev) as first-line treatment. MATERIALS/METHODS The study period covered September 2020 to December 2022 and involved 371 HCC patients treated with Atez/Bev. The values of the TMs AFP, AFP-L3, and DCP were measured upon introducing Atez/Bev. Elevations in the values of AFP (≥100 ng/mL), AFP-L3 (≥10%), and DCP (≥100 mAU/mL) were considered to indicate a positive TM. The number of positive TMs was summed up and used as the TM score, as previously proposed. Hepatic reserve function was assessed using the modified albumin-bilirubin grade (mALBI). Predictive values for prognosis were evaluated retrospectively. RESULTS A TM score of 0 was shown in 81 HCC patients (21.8%), 1 in 110 (29.6%), 2 in 112 (29.9%), and 3 in 68 (18.3%). The median overall survival (OS) times for TM scores 0, 1, 2, and 3 were not applicable [NA] (95% CI NA-NA), 24.0 months (95% CI 17.8-NA), 16.7 months (95% CI 17.8-NA), and NA (95% CI 8.3-NA), respectively (p < 0.001). The median progression-free survival (PFS) times for TM scores 0, 1, 2, and 3 were 16.5 months (95% CI 8.0-not applicable [NA]), 13.8 months (95% CI 10.6-21.3), 7.7 months (95% CI 5.3-8.9), and 5.8 months (95% CI 3.0-7.6), respectively (p < 0.001). OS was well stratified in mALBI 1/2a and mALBI 2a/2b. PFS was well stratified in mALBI 2a/2b, but not in mALBI 1/2a. CONCLUSIONS The TM score involving AFP, AFP-L3, and DCP as TMs was useful in predicting the prognosis and therapeutic efficacy in terms of OS and PFS in HCC patients administered Atez/Bev as first-line treatment.
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Affiliation(s)
- Kazunari Tanaka
- Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo 006-8555, Japan;
| | - Kunihiko Tsuji
- Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo 006-8555, Japan;
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama 790-0024, Japan; (H.O.); (F.T.)
| | - Toshifumi Tada
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji 670-8540, Japan; (T.T.); (S.N.)
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon 791-0295, Japan; (M.H.); (Y.K.); (Y.H.)
| | - Kazuya Kariyama
- Department of Hepatology, Okayama City Hospital, Okayama 700-0962, Japan; (K.K.); (K.N.)
| | - Joji Tani
- Department of Gastroenterology and Hepatology, Kagawa University, Kagawa 761-0795, Japan; (J.T.); (A.M.)
| | - Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo 113-8603, Japan (N.I.); (T.O.); (T.A.)
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu 760-8557, Japan; (K.T.); (A.T.); (T.N.)
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Asahi 289-2511, Japan;
| | - Shinya Fukunishi
- Department of Gastroenterology, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan; (S.F.); (K.Y.); (H.N.)
| | - Toru Ishikawa
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata 950-1104, Japan; (T.I.); (M.I.)
| | - Kazuto Tajiri
- Department of Gastroenterology, Toyama University Hospital, Toyama 930-0194, Japan;
| | - Hironori Ochi
- Center for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Matsuyama 790-8524, Japan;
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki 503-8502, Japan;
| | - Chikara Ogawa
- Department of Gastroenterology, Japanese Red Cross Takamatsu Hospital, Takamatsu 760-0017, Japan;
| | - Takashi Nishimura
- Department of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya 663-8501, Japan; (T.N.); (H.I.)
| | - Takeshi Hatanaka
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi 371-0821, Japan;
| | - Satoru Kakizaki
- Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki 370-0829, Japan;
| | - Noritomo Shimada
- Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa 277-0863, Japan;
| | - Kazuhito Kawata
- Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu 565-0871, Japan;
| | - Atsushi Naganuma
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki 370-0829, Japan;
| | - Hisashi Kosaka
- Department of Surgery, Kansai Medical University, Hirakata 573-1010, Japan; (H.K.); (M.K.)
| | - Tomomitsu Matono
- Department of Hepatology, St. Mary’s Hospital, Himeji 670-0801, Japan;
| | - Hidekatsu Kuroda
- Division of Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan;
| | - Yutaka Yata
- Department of Gastroenterology, Hanwa Memorial Hospital, Osaka 558-0041, Japan;
| | - Hideko Ohama
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama 790-0024, Japan; (H.O.); (F.T.)
| | - Fujimasa Tada
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama 790-0024, Japan; (H.O.); (F.T.)
| | - Kazuhiro Nouso
- Department of Hepatology, Okayama City Hospital, Okayama 700-0962, Japan; (K.K.); (K.N.)
| | - Asahiro Morishita
- Department of Gastroenterology and Hepatology, Kagawa University, Kagawa 761-0795, Japan; (J.T.); (A.M.)
| | - Akemi Tsutsui
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu 760-8557, Japan; (K.T.); (A.T.); (T.N.)
| | - Takuya Nagano
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu 760-8557, Japan; (K.T.); (A.T.); (T.N.)
| | - Norio Itokawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo 113-8603, Japan (N.I.); (T.O.); (T.A.)
| | - Tomomi Okubo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo 113-8603, Japan (N.I.); (T.O.); (T.A.)
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo 113-8603, Japan (N.I.); (T.O.); (T.A.)
| | - Keisuke Yokohama
- Department of Gastroenterology, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan; (S.F.); (K.Y.); (H.N.)
| | - Hiroki Nishikawa
- Department of Gastroenterology, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan; (S.F.); (K.Y.); (H.N.)
| | - Michitaka Imai
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata 950-1104, Japan; (T.I.); (M.I.)
| | - Yohei Koizumi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon 791-0295, Japan; (M.H.); (Y.K.); (Y.H.)
| | - Shinichiro Nakamura
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji 670-8540, Japan; (T.T.); (S.N.)
| | - Hiroko Iijima
- Department of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya 663-8501, Japan; (T.N.); (H.I.)
| | - Masaki Kaibori
- Department of Surgery, Kansai Medical University, Hirakata 573-1010, Japan; (H.K.); (M.K.)
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon 791-0295, Japan; (M.H.); (Y.K.); (Y.H.)
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Ogaki 503-8550, Japan;
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Yu J, Park R, Kim R. Promising Novel Biomarkers for Hepatocellular Carcinoma: Diagnostic and Prognostic Insights. J Hepatocell Carcinoma 2023; 10:1105-1127. [PMID: 37483311 PMCID: PMC10362916 DOI: 10.2147/jhc.s341195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Accepted: 07/07/2023] [Indexed: 07/25/2023] Open
Abstract
The systemic therapy landscape for hepatocellular carcinoma is rapidly evolving, as the recent approvals of checkpoint inhibitor-based regimens such as atezolizumab-bevacizumab and durvalumab-tremelimumab in advanced disease have led to an expanding therapeutic armamentarium. The development of biomarkers, however, has not kept up with the approvals of new agents. Nevertheless, biomarker research for hepatocellular carcinoma has recently been growing at a rapid pace. The most active areas of research are biomarkers for early detection and screening, accurate prognostication, and detection of minimal residual disease following curative intent therapies, and, perhaps most importantly, predictive markers to guide selection and sequencing of the individual agents, including tyrosine kinase inhibitors and immunotherapy. In this review, we briefly summarize the recent developments in systemic therapeutics for hepatocellular carcinoma, introduce the key completed and ongoing prospective and retrospective studies evaluating diagnostic, prognostic, and predictive biomarkers with high clinical relevance, highlight several potentially important areas of future research, and share our insights for each biomarker.
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Affiliation(s)
- James Yu
- Division of Hematology and Medical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Robin Park
- Division of Hematology and Medical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Richard Kim
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
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Ueno M, Kosaka H, Iida H, Ida Y, Aoi K, Mori H, Miyamoto A, Nishida Y, Hayami S, Kawai M, Kaibori M. Response Prediction Model of Atezolizumab plus Bevacizumab in Patients with Unresectable Hepatocellular Carcinoma: Multicenter Retrospective Study. Oncology 2023; 101:565-574. [PMID: 37276856 DOI: 10.1159/000531317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 05/17/2023] [Indexed: 06/07/2023]
Abstract
INTRODUCTION Atezolizumab plus bevacizumab (ATZ+BV) treatment has become the first-line regimen for unresectable hepatocellular carcinoma (u-HCC). Prediction of response to it might be clinically beneficial. Using peripheral blood parameters, we aimed to construct a prediction model for ATZ+BV treatment. METHODS Clinical records of 119 patients with u-HCC treated by ATZ+BV were retrospectively analyzed. The primary outcome measurement was defined as any-size reduction at the initial image evaluation. Using baseline values of peripheral blood parameters, a prediction model was constructed by univariate and multivariate logistic regression analysis. Validation was performed internally by bootstrap method. RESULTS The primary outcome was achieved in 46 patients. Univariate analysis showed that C-reactive protein (CRP), alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were possible predictors. CRP and DCP, and NLR and PLR had correlation (correlation coefficient >0.3), so we used CRP and NLR as representative factors, respectively. Multivariate analysis constructed the following prediction model: Logit = 1.62-0.61×[CRP] -0.38×[Log10AFP] -0.37×[NLR]. Bootstrapped median (95% confidence interval) of coefficients of CRP, Log10AFP, NLR were -0.64 (-1.46 ∼ -0.11), -0.40 (-0.82 ∼ -0.03), and -0.38 (-0.74 ∼ -0.05), respectively. The area under the receiver operating characteristic curve (95% confidence interval) was 0.73 (0.60-0.80). Median overall survival of the favorably and unfavorably predicted groups were 17.0 and 11.0 months (p = 0.03), respectively. DISCUSSION In patients with u-HCC treated by ATZ+BEV, a prediction model constructed using baseline values of CRP, AFP, and NLR had impact on any-size reduction at the initial image evaluation and on prognosis.
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Affiliation(s)
- Masaki Ueno
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Hisashi Kosaka
- Department of Surgery, Kansai Medical University Hirakata Hospital, Osaka, Japan
| | - Hiroya Iida
- Department of Surgery, Shiga University of Medical Science, Otsu, Japan
| | - Yoshiyuki Ida
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Kazunori Aoi
- Third Department of Internal Medicine, Kansai Medical University Hirakata Hospital, Osaka, Japan
| | - Haruki Mori
- Department of Surgery, Shiga University of Medical Science, Otsu, Japan
| | - Atsushi Miyamoto
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Yuko Nishida
- Department of Pharmacy, Kansai Medical University Hirakata Hospital, Osaka, Japan
| | - Shinya Hayami
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Manabu Kawai
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Masaki Kaibori
- Department of Surgery, Kansai Medical University Hirakata Hospital, Osaka, Japan
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Xu FQ, Zhang Z, Hu A, Huang DS. Circulating biomarkers for diagnosis and management of hepatocellular carcinoma. Shijie Huaren Xiaohua Zazhi 2023; 31:404-411. [DOI: 10.11569/wcjd.v31.i10.404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/26/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, but the prognosis of HCC patients is poor due to the difficulty of early diagnosis and high recurrence rate. Therefore, it is particularly important to seek effective methods for early diagnosis and early recurrence monitoring after treatment. Circulating biomarkers play an important role in the diagnosis, progression monitoring, and prognosis evaluation of HCC. In recent years, with the discovery of a variety of new biomarkers, the development of biomarkers-related models, and the emergence of liquid biopsy technology, the diagnosis and treatment of HCC have been greatly improved. This article reviews the latest research advances of biomarkers in the diagnosis and treatment of HCC, aiming to provide new ideas for improving the prognosis of HCC patients.
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Zhuang BW, Li W, Qiao B, Zhang N, Lin MX, Wang W, Kuang M, Lu MD, Xie XY, Xie XH. Preoperative prognostic value of alfa-fetoprotein density in patients with hepatocellular carcinoma undergoing radiofrequency ablation. Int J Hyperthermia 2022; 39:1143-1151. [PMID: 36039777 DOI: 10.1080/02656736.2022.2116491] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022] Open
Abstract
OBJECTIVES To examine the prognostic value of preoperative alfa-fetoprotein (AFP) density and other clinical factors in patients undergoing percutaneous radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC). METHODS From January 2010 to December 2018, a total of 543 patients undergoing RFA for HCC meeting the Milan criteria were included at our institution. AFP density was calculated as absolute AFP pre-ablation divided by the total volume of all HCC lesions. The survival rates according to AFP density were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox proportional-hazards regression analyses were used to assess predictors of overall survival (OS) and progression-free survival (PFS). RESULTS The Kaplan-Meier 1-, 3-, and 5-year OS rates were 98.8%, 88.5%, and 70.4%, respectively, for the low AFP density group, and 98.3%, 74.9%, and 49.4%, respectively, for the high AFP density group. The corresponding PFS rates were 78.9%, 56.7%, and 40.9% (low AFP density group), and 63.6%, 40.8%, and 27.5% (high AFP density group). High AFP density was associated with significantly reduced PFS and OS (both p < 0.001). Multivariate analysis suggested that AFP density was a predictor of OS and PFS. CONCLUSIONS Serum AFP density may serve as a promising predictor of survival in patients with HCC undergoing RFA. High AFP density could identify patients who might be prone to recurrence or progression and need close surveillance.
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Affiliation(s)
- Bo-Wen Zhuang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Wei Li
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Bin Qiao
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Nan Zhang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Man-Xia Lin
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Wei Wang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Ming Kuang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Ming-De Lu
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xiao-Yan Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xiao-Hua Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
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Yoh T, Seo S, Ogiso S, Morino K, Fukumitsu K, Ishii T, Nakamoto Y, Taura K. Quantitative assessment of microvascular invasion in hepatocellular carcinoma using preoperative serological and imaging markers. HPB (Oxford) 2021; 23:1039-1045. [PMID: 33262049 DOI: 10.1016/j.hpb.2020.10.024] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 10/05/2020] [Accepted: 10/07/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND The aim of this study was to establish a quantitative equation to predict microvascular invasion (MVI) for patients with resectable hepatocellular carcinoma (HCC). METHODS This retrospective study included 219 patients with resected HCC from 2004 to 2015. All had available three pre-operative serological markers (alfa-feto protein (AFP), fucosylated AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP)), and one imaging marker (tumor to liver ratio of SUVmax (TLR) by 18F-FDG-PET). A multiple linear regression model for predicting MVI was developed (2004-2009, n = 111) and then validated (2010-2015, n = 108). Further, impact on the obtained model on survival outcomes was assessed. RESULTS Using the derivation cohort, following equation was developed; MVI probability (%) = 14.2 × log10DCP + 9.9 × TLR - 22.0. This model resulted in an area under receiver operating characteristic curve (ROC) of 0.806 and 0.751, in the derivation and validation cohort, respectively. Furthermore, MVI probability ≥40% determined by ROC analysis was associated with worse overall survival and recurrence-free survival in the derivation and the validation cohort (all p < 0.05). CONCLUSION A quantitative model, using DCP and TLR, was able to preoperatively predict with good performance MVI and long-term outcomes in patients with HCC after liver resection.
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Affiliation(s)
- Tomoaki Yoh
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Satoru Seo
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
| | - Satoshi Ogiso
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Koshiro Morino
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Ken Fukumitsu
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takamichi Ishii
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yuji Nakamoto
- Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University, Kyoto, Japan
| | - Kojiro Taura
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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11
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Pan YX, Sun XQ, Hu ZL, Xie W, Nie KX, Fang AP, Zhang YY, Fu YZ, Chen JB, Wang JC, Wang X, Zhang YJ, Hu DD, Chen MS. Prognostic Values of Alpha-Fetoprotein and Des-Gamma-Carboxyprothrombin in Hepatocellular Carcinoma in China: An Analysis of 4792 Patients. J Hepatocell Carcinoma 2021; 8:657-670. [PMID: 34235104 PMCID: PMC8243598 DOI: 10.2147/jhc.s316223] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 06/02/2021] [Indexed: 12/24/2022] Open
Abstract
Background The importance of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) in hepatocellular carcinoma (HCC) has been studied extensively in Japan, where hepatitis C virus is the predominant aetiology of HCC. The clinical profiles of HCC regarding the state of AFP and DCP in a hepatitis B virus epidemic area have not been comprehensively investigated, and the value of these tumour markers in evaluating the response to treatment and the detection of recurrence has yet to be determined. Patients and Methods A total of 4792 patients treated in our centre were continuously analysed regarding accessible AFP and DCP data pre- and posttreatment. Baseline characteristics were summarized, and comparisons of progression-free survival (PFS) and overall survival (OS) rates were made independently. The prognostic significance of each factor was tested with the Cox proportional hazards model. Patients who had AFP and DCP data pretreatment, pre- and posttreatment, and those who were continuously monitored more than twice were analysed separately. Results A total of 2600 patients (53.4%) were positive for AFP and DCP; 362 (7.6%) and 1211 (25.3%) patients were AFP- or DCP-positive, respectively, and 619 patients (12.9%) were negative for both AFP and DCP. Patients in the AFP single-positive or double-negative groups had the best OS (P<0.001). Patients with less than 50% responses in AFP and DCP after treatments suffered from worse prognostic survival (P<0.001). In the multivariate analysis, elevated AFP and DCP were identified as independent prognostic factors of PFS and OS. In addition, different tumour markers were related to different clinical and pathological traits. Conclusion The present study comprehensively explored the clinical value of classical tumour markers for HCC using the “point-to-line” method. Positivity of pretreatment AFP and DCP or less than 50% treatment response rates exhibited more aggressive HCC, resulting in poor PFS and OS in HCC patients.
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Affiliation(s)
- Yang-Xun Pan
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.,Department of Oncology-Pathology, Karolinska Institutet, Solna, 17165, Sweden
| | - Xu-Qi Sun
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China
| | - Zi-Li Hu
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China
| | - Wa Xie
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China
| | - Ke-Xin Nie
- Real World Study Team, BaseBit.ai, Shanghai, 200050, People's Republic of China
| | - Ai-Ping Fang
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China
| | - Ying-Yao Zhang
- Real World Study Team, BaseBit.ai, Shanghai, 200050, People's Republic of China
| | - Yi-Zhen Fu
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China
| | - Jin-Bin Chen
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China
| | - Jun-Cheng Wang
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China
| | - Xin Wang
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China
| | - Yao-Jun Zhang
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China
| | - Dan-Dan Hu
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China
| | - Min-Shan Chen
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China
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12
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Ueno M, Hayami S, Kawai M, Hirono S, Okada KI, Miyazawa M, Kitahata Y, Miyamoto A, Suzaki N, Nakamura M, Yamaue H. Prognostic impact of adjuvant chemolipiodolization and treatment frequency on patients with hepatocellular carcinoma after hepatectomy: Prospective study with historical control group. Surg Oncol 2020; 36:99-105. [PMID: 33321415 DOI: 10.1016/j.suronc.2020.12.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 11/23/2020] [Accepted: 12/06/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Reducing or minimizing metastatic recurrence is a consideration in prolongation of survival of patients with hepatocellular carcinoma. We previously proposed single adjuvant chemolipiodolization (ACL) as a possible adjuvant treatment. The current study aims to further improve prognosis by performing ACL three times (sequential-ACL). METHODS We examined the prognostic impact of sequential-ACL compared with our historical cohort groups: resection alone (non-ALC) and single-ACL. We evaluated recurrence-free survival (RFS), recurrence pattern, and overall survival. Multivariate prognostic analyses were used to adjust baseline bias between three treatment groups. RESULTS Non-ACL (n = 64), single-ACL (n = 137), and sequential-ACL (n = 95) showed 40, 54, and 62% of two-year RFS rates (P = 0.03 and P = 0.007 compared with non-ACL). Recurrence pattern beyond Milan criteria was frequently observed in the non-ACL group (P = 0.003). Five-year overall survival rates of these three groups were 53, 69, and 77% (P = 0.02 and 0.002 compared with non-ACL). Single- and sequential-ACL were selected as independent favorable factors for five-year overall survival; their hazard ratios (95% confidence interval) were 0.61 (0.37-0.99) and 0.48 (0.26-0.86). However, compared with single-ACL, there was no additional prognostic effects of sequential-ACL. CONCLUSIONS Single- and sequential-ACL treatment both showed better RFS and overall survival with minimized recurrence patterns than resection alone. There was not sufficient additional benefit by sequential-ACL, however, over single-ACL. Single-ACL might therefore be appropriate as an adjuvant therapy.
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Affiliation(s)
- Masaki Ueno
- Second Department of Surgery, Wakayama Medical University, Japan.
| | - Shinya Hayami
- Second Department of Surgery, Wakayama Medical University, Japan
| | - Manabu Kawai
- Second Department of Surgery, Wakayama Medical University, Japan
| | - Seiko Hirono
- Second Department of Surgery, Wakayama Medical University, Japan
| | - Ken-Ichi Okada
- Second Department of Surgery, Wakayama Medical University, Japan
| | - Motoki Miyazawa
- Second Department of Surgery, Wakayama Medical University, Japan
| | - Yuji Kitahata
- Second Department of Surgery, Wakayama Medical University, Japan
| | - Atsushi Miyamoto
- Second Department of Surgery, Wakayama Medical University, Japan
| | - Norihiko Suzaki
- Second Department of Surgery, Wakayama Medical University, Japan
| | - Masashi Nakamura
- Second Department of Surgery, Wakayama Medical University, Japan
| | - Hiroki Yamaue
- Second Department of Surgery, Wakayama Medical University, Japan
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13
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Chen Y, He C, Wen T, Yan L, Yang J. The prognostic value of aspartate aminotransferase-to-lymphocyte ratio index in early-stage hepatocellular carcinoma after hepatectomy: A propensity-score matched analysis. Asia Pac J Clin Oncol 2020; 17:e238-e248. [PMID: 33124200 DOI: 10.1111/ajco.13458] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Accepted: 08/02/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND An elevated preoperative aspartate aminotransferase-to-lymphocyte ratio index (ALRI) may predict poor survival in various cancers. However, the prognostic value of aminotransferase-to-lymphocyte ratio index (ALRI) in patients with hepatocellular carcinoma (HCC) remains to be determined. MATERIALS AND METHODS A retrospective cohort study was conducted among 983 patients with HCC in our hospital from February 2007 to March 2016. A propensity-score matching (PSM) was performed to correct the selection bias and confounding factors. The risk of death and recurrence was plotted over aminotransferase-to-lymphocyte ratio index (ALRI) using the locally weighted scatterplot smoothing (LOWESS)-smoothed fit curve. Time-dependent receiver operating characteristic (ROC) and Kaplan-Meier method analysis was utilized to the role of aminotransferase-to-lymphocyte ratio index (ALRI) in HCC. Multivariate analysis was conducted to identify independent prognostic factors associated with overall survival (OS) and recurrence-free survival (RFS). RESULTS With the increase of aminotransferase-to-lymphocyte ratio index (ALRI), the risk of recurrence and death in HCC patients increases. In time-dependent ROC analysis, the AUC of aminotransferase-to-lymphocyte ratio index (ALRI) for predicting 1-, 3- and 5-year OS were 0.668 (95% CI: 0.596-0.740), 0.605 (95% CI: 0.560-0.649) and 0.613 (95% CI: 0.570-0.656), respective. The AUC of aminotransferase-to-lymphocyte ratio index (ALRI) for predicting 1-, 3- and 5-year RFS were 0.598 (95% CI: 0.555-0.641), 0.590 (95% CI: 0.552-0.628) and 0.604 (95% CI: 0.562-0.646), respectively. HCC patients with high aminotransferase-to-lymphocyte ratio index (ALRI) had a poor overall survival. Moreover, cox regression analysis revealed that aminotransferase-to-lymphocyte ratio index (ALRI) was an independent factor affecting the prognosis of HCC patients. CONCLUSIONS Elevated preoperative aminotransferase-to-lymphocyte ratio index (ALRI) is a noninvasive, simple, and effective predictor in the prognosis of patients with HCC.
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Affiliation(s)
- Yanyu Chen
- Department of Hepatobiliary Surgery, Fuling Central Hospital, Chongqing, 408000, China
| | - Chao He
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Tianfu Wen
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Lvnan Yan
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Jiayin Yang
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
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Piñero F, Dirchwolf M, Pessôa MG. Biomarkers in Hepatocellular Carcinoma: Diagnosis, Prognosis and Treatment Response Assessment. Cells 2020; 9:E1370. [PMID: 32492896 PMCID: PMC7349517 DOI: 10.3390/cells9061370] [Citation(s) in RCA: 293] [Impact Index Per Article: 58.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 05/28/2020] [Accepted: 05/28/2020] [Indexed: 02/08/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the main cancer-related causes of death worldwide. Thus, there is a constant search for improvement in screening, diagnosis, and treatment strategies to improve the prognosis of this malignancy. The identification of useful biomarkers for surveillance and early HCC diagnosis is still deficient, with available serum biomarkers showing low sensitivity and heterogeneous specificity despite different cut-off points, even when assessed longitudinally, or with a combination of serum biomarkers. In contrast, HCC biomarkers used for prognostic (when associated with clinical outcomes) or predictive purposes (when associated with treatment response) may have an increased clinical role in the near future. Furthermore, some serum biomarkers are already implicated as a treatment selection tool, whether to provide access to certain therapies or to assess clinical benefit after treatment. In the present review we will discuss the clinical utility and foreseen future of HCC biomarkers implicated in surveillance, diagnosis, prognosis, and post-treatment assessment.
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Affiliation(s)
- Federico Piñero
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, School of Medicine, Austral University, B1629AHJ Buenos Aires, Argentina;
- Latin American Liver Research Educational and Awareness Network (LALREAN), B1629AHJ Buenos Aires, Argentina
| | - Melisa Dirchwolf
- Liver Unit, Hospital Privado de Rosario, 2000 Rosario, Santa Fe, Argentina;
| | - Mário G. Pessôa
- Division of Gastroenterology and Hepatology, University of São Paulo School of Medicine, 05403-000 São Paulo, Brazil
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15
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Park GC, Hwang S, Park YH, Choi JU. Validation of prognostic impact of ADV score for resection of hepatocellular carcinoma: analysis using Korea Liver Cancer Registry Database. Ann Surg Treat Res 2020; 98:235-246. [PMID: 32411628 PMCID: PMC7200605 DOI: 10.4174/astr.2020.98.5.235] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 01/15/2020] [Accepted: 03/06/2020] [Indexed: 11/30/2022] Open
Abstract
Purpose We aimed to validate the prognostic predictive power of ADV score (α-FP-des-γ-carboxyprothrombin [DCP]-tumor volume [TV] score, calculated as α-FP [ng/mL] × DCP [mAU/mL] × TV [mL] and expressed in log10) for predicting patient survival after resection of hepatocellular carcinoma (HCC). Methods This study included 1,390 patients with HCC registered in the Korea Liver Cancer Registry. Patients underwent hepatic resection between 2008 and 2012 and were followed up until December 2016. They were divided into 4 groups according to the number of tumors and preoperative treatment. Results There was no significant correlation among α-FP, DCP, and TV values (r2 ≤ 0.04, P < 0.001). In group 1 with single treatment-naive tumor (n = 1,154), patient stratification with postoperative ADV 1log-interval and cutoffs of 5log, 7log, and 10log showed great prognostic contrast (P < 0.001). In group 2 with multiple treatment-naive tumors (n = 170), patient stratification with postoperative ADV 1log-interval and above-mentioned 3 cutoffs also showed great prognostic contrast (P < 0.001). In group 3 (n = 50) and group 4 (n = 16) with preoperative-treated tumors, patient stratification with postoperative ADV 1log-interval and above-mentioned 3 cutoffs showed noticeable prognostic contrast (P ≤ 0.031). Preoperative ADV score based on preoperative findings also showed great prognostic contrast in 1,106 patients preoperatively diagnosed as having single treatment-naive tumor (P < 0.001). Confining patients to tumor-node-metastasis stages I and II (n = 1,072) as well as Barcelona Clinic Liver Cancer stage 0 and A (n = 862), postoperative ADV cutoffs showed further prognostic stratification. Conclusion This validation study strongly suggests that ADV score is an integrated surrogate marker for postresection prognosis in patients with HCC.
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Affiliation(s)
- Gil-Chun Park
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yo-Han Park
- Department of Surgery, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Jin-Uk Choi
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Daily decrease of post-operative alpha-fetoprotein by 9% discriminates prognosis of HCC: A multicenter retrospective study. Aging (Albany NY) 2019; 11:11111-11123. [PMID: 31829979 PMCID: PMC6932889 DOI: 10.18632/aging.102513] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Accepted: 11/18/2019] [Indexed: 12/12/2022]
Abstract
Background: Mixed evidence challenges preoperative alpha-fetoprotein (AFP) as an independent prognostic factor for patients with hepatocellular carcinoma (HCC) after hepatectomy. Results: Daily post-operative decrease of AFP by 9% as compared to the preoperative level (A09) were selected as the Cut-off. The Kaplan-Meier curve showed that A09 was significantly different for OS (P=0.043) and RFS (P=0.03). A decrease in risk by 54% was observed for OS and 32% for RFS in the at-risk population (A09>9%). A better concordance was observed after adding A09 into TNM and BCLC staging systems. Moreover, a consistent concordance was observed in the internal (FDZS5:0.63; FDZS3:0.608) and external (FDZS5:0.85; FDZS3:0.762) validation cohorts, suggesting its prognostic value in HCC population with elevated AFP. Conclusions: Decrease in perioperative serum AFP rather than preoperative AFP is an independent prognostic factor for HCC patients after hepatectomy. Cut-off A09 significantly discriminates overall and recurrence-free survival and could be interpret into TNM and BCLC staging systems to improve the stratification power for HCC patients with elevated AFP. Methods: Kaplan-Meier curve depicted the differences of overall survival (OS) and recurrence-free survival (RFS). Nomogram and concordance were employed to evaluate the superiority of the current staging system.
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17
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Hiraoka A, Michitaka K, Kumada T, Izumi N, Kadoya M, Kokudo N, Kubo S, Matsuyama Y, Nakashima O, Sakamoto M, Takayama T, Kokudo T, Kashiwabara K, Eguchi S, Yamashita T, Kudo M. Prediction of Prognosis of Intermediate-Stage HCC Patients: Validation of the Tumor Marker Score in a Nationwide Database in Japan. Liver Cancer 2019; 8:403-411. [PMID: 31768348 PMCID: PMC6873098 DOI: 10.1159/000495944] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Accepted: 12/03/2018] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND/AIM Adequate assessment of transcatheter arterial chemoembolization (TACE)-refractory status has become more important for switching treatment in intermediate-stage (BCLC-B) hepatocellular carcinoma (HCC) patients treated with TACE. The usefulness of a previously proposed tumor marker score for predicting prognosis of BCLC-B HCC patients treated with TACE was investigated. METHODS Using a nationwide database, we examined the records of 1,306 naïve BCLC-B HCC with Child-Pugh A who were treated from 2001 to 2007, after excluding those with missing data (hepatic function or tumor markers) or cases with a single large tumor. Alpha-fetoprotein (AFP) ≥100 ng/mL, fucosylated AFP (AFP-L3) ≥10%, and des-gamma-carboxy prothrombin ≥100 mAU/mL were markers used to define positive cases. The number of positive tumor markers was used as a prognostic score, and its predictive value was evaluated in a retrospective manner. RESULTS Median survival time became shorter along with increased score (0, 1, ≥2 = 4.8, 3.8, 3.2 years, respectively; p < 0.01). Tumor marker score (≥2; hazard ratio [HR] 1.675, 95% confidence interval [CI] 1.372-2.044, p < 0.001), serum levels of albumin (≥3.5 g/dL; HR 0.726, 95% CI 0.528-0.997, p = 0.048), and up-to-7 criteria (HR 1.673, 95% CI 1.400-2.000, p < 0.001) were significant prognostic factors for death in the Cox hazard multivariate analysis. CONCLUSION Tumor marker score had a useful predictive prognostic value in BCLC-B HCC treated with TACE. Especially in patients with a tumor marker score of 2 or greater, a poor therapeutic response should be expected, and appropriate judgement of TACE-refractory status is necessary.
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Affiliation(s)
- Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Kojiro Michitaka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Namiki Izumi
- Department of Gastroenterology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Masumi Kadoya
- Department of Radiology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Norihiro Kokudo
- National Center for Global Health and Medicine, Tokyo, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yutaka Matsuyama
- Department of Biostatistics, School of Public Health, University of Tokyo, Tokyo, Japan
| | - Osamu Nakashima
- Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Takashi Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Kosuke Kashiwabara
- Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tatsuya Yamashita
- Advanced Preventive Medical Research Center, Kanazawa University, Kanazawa, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University School of Medicine, Osaka, Japan
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18
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Shigekawa Y, Hayami S, Ueno M, Miyamoto A, Suzaki N, Kawai M, Hirono S, Okada KI, Hamamoto R, Yamaue H. Overexpression of KDM5B/JARID1B is associated with poor prognosis in hepatocellular carcinoma. Oncotarget 2018; 9:34320-34335. [PMID: 30344945 PMCID: PMC6188148 DOI: 10.18632/oncotarget.26144] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2018] [Accepted: 09/04/2018] [Indexed: 12/14/2022] Open
Abstract
Background & aims Hepatocellular carcinoma (HCC) has high potential for recurrence, even in curative operative cases. Although several molecular-targeting drugs have been applied to recurrent HCC, their effectiveness has been limited. This study therefore aims to develop novel cancer drugs through protein methylation. Methods We investigated the role of KDM5B/JARID1B, a member of JmjC histone demethylase, in HCC. Expression profiles of KDM5B were examined by immunohistochemical analysis in 105 HCC clinical tissue samples. To examine functional effects of KDM5B using HCC cell lines, we performed loss-of-function analysis treated with KDM5B-specific small interfering RNAs (siKDM5B). Results All HCC cases were divided into KDM5B-positive expression group (n=54) and negative expression group (n=51). In five-year overall survival, KDM5B-positive group had poorer prognosis than KDM5B-negative (61% vs 77%, p=0.047). KDM5B-positive group had much poorer prognosis than that of the negative group, especially in HCC derived from persistent infection of hepatitis B virus (HBV) or hepatitis C virus (HCV) (54% vs 78%, p=0.015). Multivariate analysis indicated that KDM5B was the strongest risk factor for poor prognosis, especially in HCC derived from HBV/HCV. Inhibition of KDM5B could significantly suppress HCC cell proliferation through no promotion from G1 to S phase. Real-time PCR and Western blotting demonstrated that E2F1/E2F2 were downstream genes of KDM5B. Conclusions Overexpression of KDM5B results in poor prognosis in HCC that especially derived from HBV/HCV. KDM5B appears to be an ideal target for the development of anti-cancer drugs.
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Affiliation(s)
- Yoshinobu Shigekawa
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan
| | - Shinya Hayami
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan
| | - Masaki Ueno
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan
| | - Atsushi Miyamoto
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan
| | - Norihiko Suzaki
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan
| | - Manabu Kawai
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan
| | - Seiko Hirono
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan
| | - Ken-Ichi Okada
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan
| | - Ryuji Hamamoto
- Division of Molecular Modification and Cancer Biology, National Cancer Center Research Institute, Tokyo, Japan
| | - Hiroki Yamaue
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan
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19
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Okabe H, Yoshizumi T, Yamashita YI, Imai K, Hayashi H, Nakagawa S, Itoh S, Harimoto N, Ikegami T, Uchiyama H, Beppu T, Aishima S, Shirabe K, Baba H, Maehara Y. Histological architectural classification determines recurrence pattern and prognosis after curative hepatectomy in patients with hepatocellular carcinoma. PLoS One 2018; 13:e0203856. [PMID: 30216361 PMCID: PMC6138409 DOI: 10.1371/journal.pone.0203856] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2018] [Accepted: 08/28/2018] [Indexed: 12/15/2022] Open
Abstract
AIM The clinical impact of pathological classification based on architectural pattern in hepatocellular carcinoma (HCC) remains elusive in spite of its well-known and common feature. METHODS The prognostic impact of pathological classification was examined with prospective database. Three hundred and eighty HCC patients who underwent curative hepatectomy as an initial treatment in Kumamoto University were enrolled as a test cohort. The outcome was confirmed with a validation cohort in Kyushu University. RESULTS Macrotrabecular (macro-T) subtype (n = 38) and compact subtype (n = 43) showed similar biological and prognostic features. Both showed higher AFP level and worse overall survival than microrabecular (micro-T) subtype (n = 266). Multivariate analysis for overall survival revealed that DCP ≥ 40, multiple tumor and macro-T/compact subtype were associated with poor overall survival (risk ratio = 2.2, 1.6 and 1.6; p = 0.002, 0.020, and 0.047, respectively). Of note, 32% of macro-T/compact subtype showed early recurrence within 1 year, which showed substantially low (5%) 5 year overall survival, whereas 16% of micro-T/PG subtype did. Twenty-one percent of macro-T/compact subtype showed multiple intrahepatic metastases (≥ 4) or distant metastases, which resulted in non-curative treatment, whereas 5% of micro-T/PG subtype did. In validation cohort, macro-T/compact subtype was an independent predictor of worse overall survival. CONCLUSION Macro-T/compact subtype is biologically discriminated from micro-T and PG subtypes due to its aggressive features and poor prognosis after curative treatment. Additional treatment with curative hepatectomy on Macro-T/compact subtype should be discussed because of high possibility of systemic residual cancer cell.
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Affiliation(s)
- Hirohisa Okabe
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
- * E-mail:
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yo-ichi Yamashita
- Department of Multidisciplinary Treatment for Gastroenterological Cancer, Kumamoto University Hospital, Kumamoto, Japan
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hiromitsu Hayashi
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Shigeki Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Shinji Itoh
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Norifumi Harimoto
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Toru Ikegami
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Hideaki Uchiyama
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Toru Beppu
- Department of Surgery, Yamaga Central Medical Center, Kumamoto, Japan
| | | | - Ken Shirabe
- Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Gunma, Japan
| | - Hideo Baba
- Department of Multidisciplinary Treatment for Gastroenterological Cancer, Kumamoto University Hospital, Kumamoto, Japan
| | - Yoshihiko Maehara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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20
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Wen T, Jin C, Facciorusso A, Donadon M, Han HS, Mao Y, Dai C, Cheng S, Zhang B, Peng B, Du S, Jia C, Xu F, Shi J, Sun J, Zhu P, Nara S, Millis JM. Multidisciplinary management of recurrent and metastatic hepatocellular carcinoma after resection: an international expert consensus. Hepatobiliary Surg Nutr 2018; 7:353-371. [PMID: 30498711 DOI: 10.21037/hbsn.2018.08.01] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is the sixth-most common cancer and the third leading cause of cancer-related death in the world. However, 40-70% patients eventually suffer from postoperative recurrence within 5 years. HCC recurrence after surgery severely affects prognosis of the patients. Nevertheless, there is an opportunity to improve patients' prognosis if doctors and researchers can recognize the importance of a standardized perioperative management and study it in clinical and pre-clinical settings. Hence, based on our own experience and published studies from other researchers, we develop this consensus regarding multidisciplinary management of locally recurrent and metastatic hepatocellular carcinoma after resection. This consensus consists of the entire course of recurrent hepatocellular carcinoma (RHCC) management, including prediction of recurrence, prevention, diagnosis, treatment and surveillance of RHCC. Consensus recommendations are presented with grades of evidences (Ia, Ib, IIa, IIb, III and IV), and strength of recommendations (A, B, C, D and E). We also develop a decision-making path for RHCC treatment, which can intuitively demonstrate the management for RHCC. It is hoped that we may make some effort to standardize the management of RHCC and ultimately understand how to improve outcomes.
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Affiliation(s)
- Tianfu Wen
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Chen Jin
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Antonio Facciorusso
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Matteo Donadon
- Department of Hepatobiliary & General Surgery, Humanitas University, Humanitas Clinical and Research Center, Milan, Italy
| | - Ho-Seong Han
- Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Yilei Mao
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Chaoliu Dai
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang 110000, China
| | - Shuqun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200433, China
| | - Bixiang Zhang
- Hepatic Surgery Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Baogang Peng
- Department of Liver Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Shunda Du
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Changjun Jia
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang 110000, China
| | - Feng Xu
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang 110000, China
| | - Jie Shi
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200433, China
| | - Juxian Sun
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200433, China
| | - Peng Zhu
- Hepatic Surgery Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Satoshi Nara
- Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo, Japan
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21
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Koga Y, Beppu T, Imai K, Kuramoto K, Miyata T, Kitano Y, Nakagawa S, Okabe H, Okabe K, Yamashita YI, Chikamoto A, Baba H. Complete remission of advanced hepatocellular carcinoma following transient chemoembolization and portal vein ligation. Surg Case Rep 2018; 4:102. [PMID: 30159613 PMCID: PMC6115322 DOI: 10.1186/s40792-018-0510-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2017] [Accepted: 08/16/2018] [Indexed: 12/15/2022] Open
Abstract
Background Macroscopic diffuse-type hepatocellular carcinoma with concomitant major portal vein tumor thrombus (PVTT) and peritoneal dissemination indicates poor prognosis. Additionally, triple-positive tumor marker status is a predictor of poor outcome even after hepatectomy. Sorafenib is recommended in such patients, but it has limited therapeutic effectiveness. Case presentation A 54-year-old man was diagnosed with a liver abscess that was treated by puncture and drainage at a regional hospital. However, the diagnosis was subsequently changed to hepatocellular carcinoma with macroscopic portal vein tumor thrombus, based on the results obtained for the triple-positive tumor markers (alpha-fetoprotein, 45,928 ng/ml; protein induced by vitamin K absence or antagonist-II, 125,350 mAU/ml; and alpha-fetoprotein-L3, 38.3%). As the patient’s liver functional reserve was not adequate for curative resection, chemoembolization was performed with a hepatic arterial infusion of cisplatin (50 mg) and 5-FU (1000 mg), followed by mild embolization with cisplatin (50 mg) suspended in lipiodol (5 ml) and starch microspheres (300 mg) containing mitomycin C (4 mg). As the thrombus had progressed to the bifurcation of the right and left portal veins, the right vein was surgically ligated. Three peritoneal nodules could be identified and were removed. Three additional rounds of hepatic arterial chemotherapy/chemoembolization were performed after the initial surgery. At the 2-year evaluation, all tumor markers were observed to have normalized and diagnostic imaging showed complete remission. Conclusions Complete remission of hepatocellular carcinoma with macroscopic portal vein tumor thrombus and peritoneal dissemination was obtained with a treatment regimen that involved four rounds of hepatic arterial infusion chemotherapy and transient chemoembolization, portal vein ligation, and the removal of peritoneal dissemination. This regimen can be recommended for patients with advanced hemiliver lesions who cannot undergo curative resection.
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Affiliation(s)
- Yuki Koga
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan.,Department of Gastroenterological Surgery, Graduate School of Life Sciences Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Toru Beppu
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan.,Department of Gastroenterological Surgery, Graduate School of Life Sciences Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Life Sciences Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Kunitaka Kuramoto
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan.,Department of Gastroenterological Surgery, Graduate School of Life Sciences Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Tatsunori Miyata
- Department of Gastroenterological Surgery, Graduate School of Life Sciences Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Yuki Kitano
- Department of Gastroenterological Surgery, Graduate School of Life Sciences Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Shigeki Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Life Sciences Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Hirohisa Okabe
- Department of Gastroenterological Surgery, Graduate School of Life Sciences Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Kazutoshi Okabe
- Department of Gastroenterological Surgery, Graduate School of Life Sciences Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Yo-Ichi Yamashita
- Department of Gastroenterological Surgery, Graduate School of Life Sciences Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Akira Chikamoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
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22
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Yasui Y, Tsuchiya K, Kurosaki M, Takeguchi T, Takeguchi Y, Okada M, Wang W, Kubota Y, Goto T, Komiyama Y, Higuchi M, Takaura K, Hayashi T, Takada H, Tamaki N, Nakanishi H, Itakura J, Takahashi Y, Asahina Y, Enomoto N, Himeno Y, Izumi N. Up-to-seven criteria as a useful predictor for tumor downstaging to within Milan criteria and Child-Pugh grade deterioration after initial conventional transarterial chemoembolization. Hepatol Res 2018; 48:442-450. [PMID: 29278654 DOI: 10.1111/hepr.13048] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 12/20/2017] [Accepted: 12/21/2017] [Indexed: 12/18/2022]
Abstract
AIM Intermediate-stage hepatocellular carcinoma varies widely in tumor burden and liver function. This study aimed to clarify the importance of subclassification by the up-to-seven criteria in both clinical course and liver function deterioration in such patients. METHODS We retrospectively analyzed 224 patients with Child-Pugh grade A who underwent initial transarterial chemoembolization (TACE) for hepatocellular carcinoma. Tumor downstaging to within the Milan criteria within 1 year and liver function worsening as Child-Pugh grade deterioration from A to B were analyzed. RESULTS The median survival time was 35.8 months. Forty-five patients had no recurrence within 1 year after initial TACE. Of the 179 patients with at least one recurrence within a year, 44 (25%) achieved tumor downstaging to within the Milan criteria and showed significantly longer survival than non-downstaged ones (P = 0.02). Logistic regression univariate analysis revealed that up-to-seven criteria fulfillment was associated with tumor downstaging to within the Milan criteria (odds ratio 2.6; P = 0.007). The median deterioration time was 26.7 months. Multivariate analysis revealed that beyond the up-to-seven criteria (hazard ratio [HR] 1.9; P = 0.005) was an independent factor associated with Child-Pugh grade deterioration, along with serum albumin (HR 1.54; P = 0.01), serum bilirubin (HR 1.49; P = 0.02), and prothrombin time (HR 1.54; P = 0.04). CONCLUSIONS The up-to-seven criteria had prognostic value and could predict non-critical recurrence and maintenance of Child-Pugh grade in patients who underwent initial conventional TACE.
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Affiliation(s)
- Yutaka Yasui
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kaoru Tsuchiya
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Takaya Takeguchi
- Department of Radiology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yuko Takeguchi
- Department of Radiology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Mao Okada
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Wan Wang
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yohei Kubota
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Tomoyuki Goto
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yasuyuki Komiyama
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.,First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Mayu Higuchi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kenta Takaura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Tsuguru Hayashi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.,Third Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Hitomi Takada
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.,First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Hiroyuki Nakanishi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Jun Itakura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yuka Takahashi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yasuhiro Asahina
- Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan
| | - Nobuyuki Enomoto
- First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Yoshiro Himeno
- Department of Radiology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
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23
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Takaya H, Kawaratani H, Seki K, Okura Y, Kitade M, Namisaki T, Sawai M, Sawada Y, Kubo T, Mitoro A, Yamao J, Yoshiji H. A Patient with Hepatocellular Carcinoma with Isolated Right Atrial Metastases. Intern Med 2017; 56:2589-2594. [PMID: 28883235 PMCID: PMC5658524 DOI: 10.2169/internalmedicine.8568-16] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Hepatocellular carcinoma (HCC) with isolated right atrial metastasis is extremely rare; most cases are considered inoperable. We herein report the case of a 74-year-old man with HCC with isolated right atrial metastases without hepatic vein invasion; the right atrial lesion was resected because of the risk of heart failure and sudden death. Postoperatively, he underwent transcatheter arterial chemoembolization and radiofrequency ablation for intrahepatic HCC. He recovered completely, with a long-term survival of 36 months. This is the first report of an HCC patient with isolated right atrial metastases without hepatic vein invasion. Tumorectomy for solitary atrial metastasis is effective for HCC patients.
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Affiliation(s)
- Hiroaki Takaya
- Third Department of Internal Medicine, Nara Medical University, Japan
| | - Hideto Kawaratani
- Third Department of Internal Medicine, Nara Medical University, Japan
| | - Kenichiro Seki
- Third Department of Internal Medicine, Nara Medical University, Japan
| | - Yasushi Okura
- Department of Endoscopy, Nara Medical University, Japan
| | - Mitsuteru Kitade
- Third Department of Internal Medicine, Nara Medical University, Japan
| | - Tadashi Namisaki
- Third Department of Internal Medicine, Nara Medical University, Japan
| | - Masayoshi Sawai
- Third Department of Internal Medicine, Nara Medical University, Japan
| | - Yasuhiko Sawada
- Third Department of Internal Medicine, Nara Medical University, Japan
| | - Takuya Kubo
- Third Department of Internal Medicine, Nara Medical University, Japan
| | - Akira Mitoro
- Third Department of Internal Medicine, Nara Medical University, Japan
| | - Junichi Yamao
- Department of Endoscopy, Nara Medical University, Japan
| | - Hitoshi Yoshiji
- Third Department of Internal Medicine, Nara Medical University, Japan
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24
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Luo LM, Xia H, Shi R, Zeng J, Liu XR, Wei M. The association between aquaporin-1 expression, microvessel density and the clinicopathological features of hepatocellular carcinoma. Oncol Lett 2017; 14:7077-7084. [PMID: 29344137 PMCID: PMC5754835 DOI: 10.3892/ol.2017.7106] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2015] [Accepted: 05/18/2017] [Indexed: 01/27/2023] Open
Abstract
The present study aimed to evaluate the effects of aquaporin-1 (AQP1) level and intratumoral microvessel density (IMD) on the clinicopathological features of patients with hepatocellular carcinoma (HCC). The AQP1 expression levels, IMD and AQP1/IMD ratios in patients with HCC were measured using a semi-quantitative immunohistochemical technique. The association between these features and clinicopathological variables were evaluated. The prognostic impact of AQP1 and IMD on overall survival (OS), and 5-year disease-free survival (DFS) of HCC patients was investigated retrospectively. P<0.05 was considered to indicate a statistically significant difference. A total of 90 cases of HCC were included in the present study. AQP1 was markedly expressed in the membranes of microvessels and small vessels, but seldom in hepatocellular carcinoma cells. Blood vessels in the tumors were markedly stained by anti-cluster of differentiation 34 antibody. AQP1 expression and IMD was significantly correlated with tumor size, histologic grade, Child-Pugh classification, microvascular invasion and tumor-node-metastasis (TNM) stage (P<0.05). Concurrently, for the 5-year DFS and OS, a larger tumor size, poorly differentiated histological grade, B and C Child-Pugh classification, presence of microvascular invasion, high TNM stage, a high AQP1 expression and a high IMD were significant risk factors for mortality. Multivariate analysis revealed that TNM stage and IMD were independent unfavorable prognostic markers for 5-year DFS (P=0.049 and P=0.025, respectively) and OS (P=0.043 and P=0.042, respectively). These data suggest that high AQP1 expression and IMD are associated with tumor progression and prognosis in HCC. The IMD level may serve as an independent indicator for the 5-year DFS and OS.
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Affiliation(s)
- Li-Min Luo
- Centre for Liver Disease, 458th Hospital of People's Liberation Army, Guangzhou, Guangdong 510602, P.R. China
| | - Hu Xia
- Department of Respiration Medicine, Zhujiang Hospital, Guangzhou, Guangdong 510282, P.R. China
| | - Rong Shi
- Clinical Laboratory, Nanshan Maternity & Child Healthcare Hospital, Shenzhen, Guangdong 518067, P.R. China
| | - Jun Zeng
- Clinical Laboratory, Nanshan Maternity & Child Healthcare Hospital, Shenzhen, Guangdong 518067, P.R. China
| | - Xin-Rui Liu
- Clinical Laboratory, Nanshan Maternity & Child Healthcare Hospital, Shenzhen, Guangdong 518067, P.R. China
| | - Min Wei
- Clinical Laboratory, Nanshan Maternity & Child Healthcare Hospital, Shenzhen, Guangdong 518067, P.R. China
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Beppu T, Nakagawa S, Nitta H, Okabe H, Kaida T, Imai K, Hayashi H, Koga Y, Kuramoto K, Hashimoto D, Yamashita YI, Chikamoto A, Ishiko T, Baba H. The Number of Positive Tumor Marker Status Is Beneficial for the Selection of Therapeutic Modalities in Patients with Hepatocellular Carcinoma. J Clin Transl Hepatol 2017; 5:165-168. [PMID: 28660154 PMCID: PMC5472937 DOI: 10.14218/jcth.2016.00055] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Revised: 04/11/2017] [Accepted: 04/13/2017] [Indexed: 12/11/2022] Open
Abstract
Hepatic resection (HR) and radiofrequency ablation (RFA) are popular local therapies for early-stage hepatocellular carcinoma (HCC). Alpha-fetoprotein, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein, and des-c-carboxy prothrombin are well-known and useful tumor markers for HCC. The positive number status of these tumor markers has recently been demonstrated as beneficial for predicting outcome for HCC patients treated with local therapy. Although the normal ranges reported have differed by institution, the positivity of tumor markers is consistent and can easily be assessed. Kumamoto and Wakayama's group clearly demonstrated the following: 1) Regardless of the degree of tumor stage, a triple-positive tumor marker profile can predict poor outcome in HCC patients undergoing HR; 2) For RFA alone, HCC patients with double- and triple-positive status, having less than three lesions and lesions ≤3 cm in diameter show comparably insufficient outcomes; 3) For HCC patients with lesions ≤5 cm in Child-Pugh grade A, HR is preferred over RFA; 4) Microvascular invasion rates increased even in the double-positive patients, while poorly differentiated HCC was frequently observed only in the triple-positive patients; and 5) RFA with chemoembolization, anatomical liver resection, and postoperative adjuvant chemoembolization or hepatic arterial chemotherapy might improve the outcome for patients with highly malignant HCC with multiple positive tumor markers. However, the impacts of these therapies still need to be evaluated in prospective comparative studies.
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Affiliation(s)
- Toru Beppu
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
- *Correspondence to: Toru Beppu, Department of Surgery, Yamaga City Medical Center, 511, Yamaga, Kumamoto 861-0593, Japan. Tel: +81-968-44-2185, Fax: +81-968-44-2420, E-mail:
| | - Shigeki Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hidetoshi Nitta
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hirohisa Okabe
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Takayoshi Kaida
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hiromitsu Hayashi
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Yuki Koga
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Kunitaka Kuramoto
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Daisuke Hashimoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Yo-ichi Yamashita
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Akira Chikamoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Takatoshi Ishiko
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
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Ryu T, Takami Y, Wada Y, Tateishi M, Matsushima H, Mikagi K, Saitsu H. Double- and Triple-Positive Tumor Markers Predict Early Recurrence and Poor Survival in Patients with Hepatocellular Carcinoma within the Milan Criteria and Child-Pugh Class A. J Gastrointest Surg 2017; 21:957-966. [PMID: 28299619 DOI: 10.1007/s11605-017-3394-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Accepted: 03/06/2017] [Indexed: 01/31/2023]
Abstract
The prognostic implications of the expression patterns of three tumor markers, alpha-fetoprotein (AFP), the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) and des-γ-carboxy prothrombin (DCP), have been evaluated in patients with hepatocellular carcinoma (HCC). From January 1994 to December 2014, 1182 consecutive patients underwent hepatic resection and surgical microwave ablation for HCC at our institution. This study analyzed 475 patients within the Milan criteria and Child-Pugh class A. Cumulative overall survival (OS) and disease-free survival (DFS) rates were analyzed relative to the number of positive tumor markers. OS and DFS at 5 years postoperatively were 85.3 and 44.2% in triple-negative patients, 79.4 and 48.0% in single-positive patients, 56.2 and 32.9% in double-positive patients, and 61.7 and 35.7% in triple-positive patients with statistical significance. OS in triple-negative or single-positive patients was 85.3%, and that in all double- or triple-positive patients was 58.0% (P < 0.0001); DFS at 5 years postoperatively in these two groups was 45.9 and 34.0%, respectively (P < 0.0013). Both double- and triple-positive tumor markers are associated with early recurrence and poor survival in HCC patients within the Milan criteria and Child-Pugh class A.
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Affiliation(s)
- Tomoki Ryu
- Department of Hepato-Biliary-Pancreatic Surgery, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama Chuo-ku, Fukuoka, 810-8563, Japan.
| | - Yuko Takami
- Department of Hepato-Biliary-Pancreatic Surgery, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama Chuo-ku, Fukuoka, 810-8563, Japan
| | - Yoshiyuki Wada
- Department of Hepato-Biliary-Pancreatic Surgery, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama Chuo-ku, Fukuoka, 810-8563, Japan
| | - Masaki Tateishi
- Department of Hepato-Biliary-Pancreatic Surgery, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama Chuo-ku, Fukuoka, 810-8563, Japan
| | - Hajime Matsushima
- Department of Hepato-Biliary-Pancreatic Surgery, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama Chuo-ku, Fukuoka, 810-8563, Japan
| | - Kazuhiro Mikagi
- Department of Hepato-Biliary-Pancreatic Surgery, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama Chuo-ku, Fukuoka, 810-8563, Japan
| | - Hideki Saitsu
- Department of Hepato-Biliary-Pancreatic Surgery, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama Chuo-ku, Fukuoka, 810-8563, Japan
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Multiplication of Tumor Volume by Two Tumor Markers Is a Post-Resection Prognostic Predictor for Solitary Hepatocellular Carcinoma. J Gastrointest Surg 2016; 20:1807-1820. [PMID: 27311982 DOI: 10.1007/s11605-016-3187-y] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2016] [Accepted: 06/07/2016] [Indexed: 01/31/2023]
Abstract
BACKGROUND We hypothesized that microvascular invasion (MVI) and post-resection prognosis in patients with solitary hepatocellular carcinoma (HCC) could be predicted using blood tumor markers and tumor volume (TV). We intended to identify a simple surrogate marker of HCC via a combination of clinical variables. METHODS This retrospective study used the strictly selected development cohort (n = 1176) and validation cohort (n = 551) containing patients who underwent curative resection of solitary HCC. RESULTS In the development cohort study, the median values were 13.7 mL for TV, 24.2 ng/mL for α-fetoprotein (AFP), and 75 mAU/mL for des-γ-carboxy prothrombin (DCP); there was no correlation among these three factors (r 2 ≤ 0.237, p < 0.001). The 1-, 3-, and 5-year rates were 22.4, 41.7, and 46.8 % for tumor recurrence and 93.6, 84.0, and 78.2 % for patient survival, respectively. Independent risk factors for both tumor recurrence and patient survival were tumor diameter >5 cm or TV >50 mL, MVI, satellite nodules, and high DCP. Multiplication of AFP, DCP, and TV (ADV score) resulted in prediction of MVI at a cutoff of 5log with sensitivity of 73.9 % and specificity of 66.7 %. Patient stratifications according to ADV score with cutoffs of 5log alone, 6log and 9log, and its combination with MVI showed significant prognostic differences (all p < 0.001). These prognostic significances were reliably reproduced in the validation cohort study (all p < 0.001). CONCLUSIONS We suggest that ADV score is an integrated surrogate marker of HCC prognosis. We believe that it can be used to predict MVI and post-resection prognosis for solitary HCC.
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Okamura Y, Sugiura T, Ito T, Yamamoto Y, Ashida R, Uesaka K. The Half-Life of Serum Des-Gamma-Carboxy Prothrombin Is a Prognostic Index of Survival and Recurrence After Liver Resection for Hepatocellular Carcinoma. Ann Surg Oncol 2016; 23:921-928. [PMID: 27638677 DOI: 10.1245/s10434-016-5570-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Indexed: 11/18/2022]
Abstract
BACKGROUND Des-γ-carboxy prothrombin (DCP) is a representative tumor marker of hepatocellular carcinoma (HCC), and its values are occasionally very high in HCC cases. The current study aimed to clarify the postoperative half-life of DCP as a prognostic factor. METHODS This retrospective study enrolled 177 patients who had undergone liver resection as an initial treatment for HCC. Three DCP half-life groups were defined as follows: within the normal range, half-life shorter than 4 days, and half-life of 4 days or longer. The overall and recurrence-free survival rates were estimated and compared among the three groups. RESULTS There were 140 patients in the group with a DCP half-life in the normal range, 19 patients in the group with a DCP half-life shorter 4 days, and 18 patients in the group with a DCP half-life of 4 days or longer. A multivariate analysis showed that only a postoperative DCP half-life of 4 days or longer was an independent prognostic risk factor for overall and recurrence-free survival (respective hazard ratios of 2.92 and 4.19; P < 0.001). The group with a preoperative DCP value lower than 1400 mAU/mL, the median value of DCP in the current study, included no patients from the group with a half-life shorter than 4 days. The overall and recurrence-free survival rates in the group with a half-life of 4 days or longer were significantly poorer (P < 0.001) than in the group that had a half-life shorter than 4 days (P = 0.002) with a preoperative DCP status of 1400 mAU/mL or more. CONCLUSIONS The current study showed for the first time that a prolonged half-life of DCP is an independent prognostic risk factor for survival and recurrence after liver resection with curative intent.
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Affiliation(s)
- Yukiyasu Okamura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
| | - Teiichi Sugiura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Takaaki Ito
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Yusuke Yamamoto
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Ryo Ashida
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan
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Nitta H, Nakagawa S, Kaida T, Arima K, Higashi T, Taki K, Okabe H, Hayashi H, Hashimoto D, Chikamoto A, Ishiko T, Beppu T, Baba H. Pre-treatment double- or triple-positive tumor markers are predictive of a poor outcome for patients undergoing radiofrequency ablation for hepatocellular carcinoma. Surg Today 2016; 47:375-384. [PMID: 27549776 DOI: 10.1007/s00595-016-1385-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Accepted: 06/23/2016] [Indexed: 02/07/2023]
Abstract
PURPOSES We evaluated the therapeutic effect of radiofrequency ablation (RFA) on hepatocellular carcinoma (HCC) according to the number of positive tumor markers. METHODS The subjects of this study were 160 patients who underwent percutaneous and surgical RFA for HCC. Patients were divided into negative (n = 51), single- (n = 69), double- (n = 31), and triple-positive (n = 9) tumor marker groups according to the pre-treatment expression of these markers. We looked for any relationships among clinical parameters, outcomes, and tumor markers. RESULTS The 3-year recurrence-free and overall survival rates of the negative, single-, double-, and triple-positive groups were 30, 19, 16, and 11 % (P = 0.02), and 94, 88, 67, and 37 % (P < 0.001), respectively. The 2-year local recurrence rates were 6.5, 0, 41.2, and 61.9 %, respectively (P < 0.001). Multivariate analysis revealed that a double- or triple-positive pre-treatment tumor marker profile was independently associated with local recurrence [hazard ratio (HR) 5.48, 95 % confidence interval (CI) 2.44-12.33, P < 0.001] and overall survival (HR 4.21, 95 % CI 1.89-9.37, P < 0.001). CONCLUSION RFA may not be suitable for patients with HCC who have pre-treatment expression of ≥two of these tumor markers.
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Affiliation(s)
- Hidetoshi Nitta
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Shigeki Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Takayoshi Kaida
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Kota Arima
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Takaaki Higashi
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Katsunobu Taki
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Hirohisa Okabe
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Hiromitsu Hayashi
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Daisuke Hashimoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Akira Chikamoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Takatoshi Ishiko
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Toru Beppu
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
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Ueno M, Nakai T, Hayashi M, Hirokawa F, Nagano H, Wada H, Kaibori M, Matsui K, Tanaka S, Yamaue H, Kubo S. Survival outcome of salvage hepatectomy in patients with local, recurrent hepatocellular carcinoma who underwent radiofrequency ablation as their first treatment. Surgery 2016; 160:661-70. [PMID: 27267547 DOI: 10.1016/j.surg.2016.04.023] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Revised: 03/24/2016] [Accepted: 04/08/2016] [Indexed: 02/08/2023]
Abstract
BACKGROUND Local recurrence is a specific problem after radiofrequency ablation of small hepatocellular carcinoma, and additional treatment is an important issue. We aimed to investigate the outcome of salvage hepatectomy in patients who develop local, recurrent hepatocellular carcinoma after treatment with radiofrequency ablation. METHODS From 2001-2013, we reviewed 58 patients from 6 university hospitals with local, recurrent hepatocellular carcinoma who underwent salvage hepatectomy after their initial radiofrequency ablation treatment. Pathologic characteristics and prognostic factors influencing overall survival were analyzed. RESULTS Noncurative resection, des-gamma carboxy prothrombin levels >40 mAU/mL, and multiple preceding treatments before salvage hepatectomy were negative prognostic factors for overall survival. The 5-year survivals for the prognostic factors were 0%, 24%, and 30%, respectively, after salvage hepatectomy, and 0%, 54%, and 54% after initial radiofrequency ablation treatment, respectively. As for the pathologic finding of local, recurrent hepatocellular carcinoma after radiofrequency ablation, vascular invasion was observed frequently in patients with increases in des-gamma carboxy prothrombin levels and with multiple preceding treatments before salvage hepatectomy with a frequency of 59% and 53%, respectively (P < .01 and .05). CONCLUSION Noncurative resection, increases in serum des-gamma carboxy prothrombin, and multiple preceding treatments were prognostic factors for subsequent salvage hepatectomy; nevertheless, survival outcomes were still acceptable when a curative salvage hepatectomy was performed. Increases in serum des-gamma carboxy prothrombin and multiple preceding treatments were positive predictors for pathologic vascular invasion. These factors should be taken into consideration when selecting treatment modalities for locally recurrent hepatocellular carcinoma following radiofrequency ablation. Repetition of unsuccessful, loco-regional treatment would appear to decrease the potential survival.
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Affiliation(s)
- Masaki Ueno
- Second Department of Surgery, Wakayama Medical University, Wakayama, Wakayama, Japan.
| | - Takuya Nakai
- Department of Surgery, Faculty of Medicine, Kinki University, Sayama, Osaka, Japan
| | - Michihiro Hayashi
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Fumitoshi Hirokawa
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Hiroaki Nagano
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Hiroshi Wada
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Masaki Kaibori
- Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan
| | - Kosuke Matsui
- Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan
| | - Shogo Tanaka
- Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Osaka City University, Osaka, Osaka, Japan
| | - Hiroki Yamaue
- Second Department of Surgery, Wakayama Medical University, Wakayama, Wakayama, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Osaka City University, Osaka, Osaka, Japan
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Cillo U, Giuliani T, Polacco M, Herrero Manley LM, Crivellari G, Vitale A. Prediction of hepatocellular carcinoma biological behavior in patient selection for liver transplantation. World J Gastroenterol 2016; 22:232-252. [PMID: 26755873 PMCID: PMC4698488 DOI: 10.3748/wjg.v22.i1.232] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Revised: 08/14/2015] [Accepted: 11/09/2015] [Indexed: 02/06/2023] Open
Abstract
Morphological criteria have always been considered the benchmark for selecting hepatocellular carcinoma (HCC) patients for liver transplantation (LT). These criteria, which are often inappropriate to express the tumor’s biological behavior and aggressiveness, offer only a static view of the disease burden and are frequently unable to correctly stratify the tumor recurrence risk after LT. Alpha-fetoprotein (AFP) and its progression as well as AFP-mRNA, AFP-L3%, des-γ-carboxyprothrombin, inflammatory markers and other serological tests appear to be correlated with post-transplant outcomes. Several other markers for patient selection including functional imaging studies such as 18F-FDG-PET imaging, histological evaluation of tumor grade, tissue-specific biomarkers, and molecular signatures have been outlined in the literature. HCC growth rate and response to pre-transplant therapies can further contribute to the transplant evaluation process of HCC patients. While AFP, its progression, and HCC response to pre-transplant therapy have already been used as a part of an integrated prognostic model for selecting patients, the utility of other markers in the transplant setting is still under investigation. This article intends to review the data in the literature concerning predictors that could be included in an integrated LT selection model and to evaluate the importance of biological aggressiveness in the evaluation process of these patients.
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Song PP, Xia JF, Inagaki Y, Hasegawa K, Sakamoto Y, Kokudo N, Tang W. Controversies regarding and perspectives on clinical utility of biomarkers in hepatocellular carcinoma. World J Gastroenterol 2016; 22:262-274. [PMID: 26755875 PMCID: PMC4698491 DOI: 10.3748/wjg.v22.i1.262] [Citation(s) in RCA: 90] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Revised: 07/27/2015] [Accepted: 10/13/2015] [Indexed: 02/06/2023] Open
Abstract
The prevalence of hepatocellular carcinoma (HCC) worldwide parallels that of persistent infection with the hepatitis B virus (HBV) and/or hepatitis C virus (HCV). According to recommendations by the World Health Organization guidelines for HBV/HCV, alpha-fetoprotein (AFP) testing and abdominal ultrasound should be performed in routine surveillance of HCC every 6 mo for high-risk patients. These examinations have also been recommended worldwide by many other HCC guidelines over the past few decades. In recent years, however, the role of AFP in HCC surveillance and diagnosis has diminished due to advances in imaging modalities. AFP was excluded from the surveillance and/or diagnostic criteria in the HCC guidelines published by the American Association for the Study of Liver Diseases in 2010, the European Association for the Study of the Liver in 2012, and the National Comprehensive Cancer Network in 2014. Other biomarkers, including the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), des-γ-carboxyprothrombin, Dickkopf-1, midkine, and microRNA, are being studied in this regard. Furthermore, increasing attention has focused on the clinical utility of biomarkers as pre-treatment predictors for tumor recurrence and as post-treatment monitors. Serum and tissue-based biomarkers and genomics may aid in the diagnosis of HCC, determination of patient prognosis, and selection of appropriate treatment. However, further studies are needed to better characterize the accuracy and potential role of these approaches in clinical practice.
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Ueno M, Hayami S, Shigekawa Y, Kawai M, Hirono S, Okada KI, Tamai H, Shingaki N, Mori Y, Ichinose M, Yamaue H. Prognostic impact of surgery and radiofrequency ablation on single nodular HCC ⩽5 cm: Cohort study based on serum HCC markers. J Hepatol 2015. [PMID: 26212030 DOI: 10.1016/j.jhep.2015.07.013] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND & AIMS Serological markers of hepatocellular carcinoma (HCC) indicate its invasiveness. We aimed to investigate whether the prognostic impact of surgical resection (SR) and radiofrequency thermal ablation (RFA) on patients with single nodular HCC ⩽5cm were different regarding positive conditions of the following three HCC markers: alpha-fetoprotein (AFP); lens culinaris agglutinin-reactive fraction of AFP; and des-γ-carboxy prothrombin. METHODS This study reviewed 296 patients with single nodular HCC ⩽5cm with Child-Pugh grade A between 2001 and 2011 (SR, n=136; RFA, n=160). Based on positive conditions of previous HCC markers (defined as non-positive, single-positive, double-positive, and triple-positive), overall survival (OS) and prognostic factors were analyzed. RESULTS Five-year OS rates of SR and RFA among all patients were 70.1% and 69.8%, respectively (p=0.14). However, when stratified by the positive conditions of three HCC markers, their rates of non-, single-, double-, and triple-positive patients were 60.6%, 78.2%, 54.2%, and 75.9% in the SR group, whereas rates were 83.3%, 75.7%, 62.2%, and 47.6% in the RFA group (p values between SR and RFA of each tumor marker condition were 0.45, 0.10, 0.77, and <0.01, respectively). Multivariate analyses showed that RFA itself became an independent prognostic factor in the triple-positive group, with an odds ratio of 1.78 (95% confidence interval, 1.16-2.72). CONCLUSIONS Positive conditions of three HCC markers differently influenced survival rates of those who underwent SR and RFA when treating single nodular HCC ⩽5cm. RFA itself became an independent prognostic risk when all three HCC markers were positive. Preoperative evaluation of multiple HCC markers might become an index for selecting treatment modalities.
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Affiliation(s)
- Masaki Ueno
- Second Department of Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8510, Japan
| | - Shinya Hayami
- Second Department of Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8510, Japan
| | - Yoshinobu Shigekawa
- Second Department of Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8510, Japan
| | - Manabu Kawai
- Second Department of Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8510, Japan
| | - Seiko Hirono
- Second Department of Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8510, Japan
| | - Ken-ichi Okada
- Second Department of Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8510, Japan
| | - Hideyuki Tamai
- Second Department of Internal Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8510, Japan
| | - Naoki Shingaki
- Second Department of Internal Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8510, Japan
| | - Yoshiyuki Mori
- Second Department of Internal Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8510, Japan
| | - Masao Ichinose
- Second Department of Internal Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8510, Japan
| | - Hiroki Yamaue
- Second Department of Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8510, Japan.
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Kamiyama T, Yokoo H, Kakisaka T, Orimo T, Wakayama K, Kamachi H, Tsuruga Y, Yamashita K, Shimamura T, Todo S, Taketomi A. Multiplication of alpha-fetoprotein and protein induced by vitamin K absence-II is a powerful predictor of prognosis and recurrence in hepatocellular carcinoma patients after a hepatectomy. Hepatol Res 2015; 45:E21-31. [PMID: 25382703 DOI: 10.1111/hepr.12451] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2014] [Revised: 10/29/2014] [Accepted: 11/05/2014] [Indexed: 02/05/2023]
Abstract
AIM To evaluate the oncological implications of multiplication of α-fetoprotein (AFP) and protein induced by vitamin K absence or antagonists-II (PIVKA-II) in patients with hepatocellular carcinoma (HCC). METHODS Data were prospectively collected from 516 consecutive patients who underwent a curative primary hepatectomy for HCC between 1998 and 2010. The AP-factor (AFP × PIVKA-II) was evaluated in relation to 2-year survival outcomes by receiver-operator curve analysis to determine the cut-off values. Patient survival, recurrence-free survival and risk factors were analyzed in accordance with the preoperative AP-factor. RESULTS The AP-factor was categorized into three groups depending on the serum concentrations of AFP and PIVKA-II as follows: AP1 (n = 206; AFP < 200 ng/mL and PIVKA-II < 100 mAU/mL), AP2 (n = 152; AFP × PIVKA-II < 10(5) ) and AP3 (n = 158; AFP × PIVKA-II ≥ 10(5) ). The AP-factor was found to be significantly related to pathological factors such as differentiation, portal vein invasion, hepatic vein invasion and intrahepatic metastasis. Multivariate analysis was performed to identify the risk factors for survival and recurrence. Albumin, AP-factor and pathological factors including portal vein invasion, hepatic vein invasion and intrahepatic metastasis are independent risk factors for survival. Tumor number, AP-factor, and a non-cancerous liver were determinants of recurrence. CONCLUSION The AP-factor is closely related to differentiation and microscopic vascular invasion, and was selected by multivariate analysis as an independent factor for survival and recurrence, in HCC. Patients hopeful of obtaining good outcomes after a hepatectomy could be selected by the AP-factor evaluation.
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Affiliation(s)
- Toshiya Kamiyama
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Hideki Yokoo
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Tatsuhiko Kakisaka
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Tatsuya Orimo
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Kenji Wakayama
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Hirofumi Kamachi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Yosuke Tsuruga
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Kenichiro Yamashita
- Departments of Transplantation Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Tsuyoshi Shimamura
- Department of Organ Transplantation, Hokkaido University Hospital, Sapporo, Japan
| | - Satoru Todo
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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Schütte K, Schulz C, Link A, Malfertheiner P. Current biomarkers for hepatocellular carcinoma: Surveillance, diagnosis and prediction of prognosis. World J Hepatol 2015; 7:139-149. [PMID: 25729470 PMCID: PMC4342597 DOI: 10.4254/wjh.v7.i2.139] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2014] [Revised: 11/21/2014] [Accepted: 12/10/2014] [Indexed: 02/06/2023] Open
Abstract
Biomarkers for surveillance, diagnosis and prediction of prognosis in patients with hepatocellular carcinoma (HCC) are currently not ready for introduction into clinical practice because of limited sensitivity and specificity. Especially for the early detection of small HCC novel biomarkers are needed to improve the current effectiveness of screening performed by ultrasound. The use of high-throughput technologies in hepatocellular research allows to identify molecules involved in the complex pathways in hepatocarcinogenesis. Several invasive and non-invasive biomarkers have been identified already and have been evaluated in different clinical settings. Gene signatures with prognostic potential have been identified by gene expression profiling from tumor tissue. However, a single “all-in-one” biomarker that fits all-surveillance, diagnosis, prediction of prognosis-has not been found so far. The future of biomarkers most probably lies in a combination of non-invasive biomarkers, imaging and clinical parameters in a surveillance setting. Molecular profiling of tumorous and non-tumorous liver tissue may allow a prediction of prognosis for the individual patient and hopefully clear the way for individual treatment approaches. This article gives an overview on current developments in biomarker research in HCC with a focus on currently available and novel biomarkers, in particular on microRNA.
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The tumor marker score is an independent predictor of survival in patients with recurrent hepatocellular carcinoma. Surg Today 2014; 45:1513-20. [PMID: 25527455 DOI: 10.1007/s00595-014-1102-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2014] [Accepted: 11/25/2014] [Indexed: 01/03/2023]
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Kudo A, Matsumura S, Ban D, Irie T, Ochiai T, Tanaka S, Arii S, Tanabe M. Does the preoperative alpha-fetoprotein predict the recurrence and mortality after hepatectomy for hepatocellular carcinoma without macrovascular invasion in patients with normal liver function? Hepatol Res 2014; 44:E437-46. [PMID: 24690156 DOI: 10.1111/hepr.12335] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2014] [Revised: 03/25/2014] [Accepted: 03/26/2014] [Indexed: 12/24/2022]
Abstract
AIM It has been highly controversial whether elevated serum α-fetoprotein (AFP) level before hepatectomy predicts recurrence and mortality of patients with hepatocellular carcinoma (HCC) or not. This study is to identify whether the index predicts recurrence and mortality after hepatectomy in HCC. METHODS Of 568 consecutive patients, 342 with normal liver function (Child-Pugh score, 5) and no macrovascular invasion were enrolled between April 2000 and March 2013. Multivariate analysis was performed to identify risk factors for disease-free survival (DFS) and overall survival (OS). RESULTS In multivariate analysis, the elevated serum AFP level was an independent risk factor for DFS (hazard ratio [HR], 1.9; P < 0.0001) and OS (HR, 2.0; P < 0.0001). Histological hepatic venous tumor thrombus was also an independent risk factor for DFS (HR, 2.6; P < 0.0001) and OS (HR, 2.5; P = 0.001). Anatomical resection decreases the risk factor for recurrence after hepatectomy (HR, 0.6; P = 0.003), though it did not decrease the risk for OS (P = 0.3). At 5 years, DFS rates were 42% and 21% (P < 0.0001) and OS rates were 75% and 46% among patients with low and high AFP levels, respectively (P < 0.0001). The area under the receiver-operator curves (AUROC) of serum AFP and des-γ-carboxy prothrombin were 0.65 and 0.58 for DFS and 0.65 and 0.57 for OS, respectively. Tumor size was the best predictor of microvascular invasion (AUROC, 0.70, P < 0.0001). CONCLUSION Serum AFP was a highly reliable index for DFS and OS.
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Affiliation(s)
- Atsushi Kudo
- Department of Hepatobiliary Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
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Nakagawa S, Beppu T, Okabe H, Sakamoto K, Kuroki H, Mima K, Nitta H, Imai K, Hayashi H, Sakamoto Y, Hashimoto D, Chikamoto A, Ishiko T, Watanabe M, Baba H. Triple positive tumor markers predict recurrence and survival in early stage hepatocellular carcinoma. Hepatol Res 2014; 44:964-74. [PMID: 24245496 DOI: 10.1111/hepr.12277] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2013] [Revised: 10/17/2013] [Accepted: 11/10/2013] [Indexed: 12/13/2022]
Abstract
AIM Hepatectomy is feasible for patients with hepatocellular carcinoma (HCC) with good hepatic function who meet the Milan criteria. Several studies have indicated that tumor markers of HCC, α-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP percentage and protein induced by vitamin K absence/antagonist-II were good predictors of malignant potential. It is important to identify highly malignant cases of HCC, and the aim of this study was to clarify the impact of triple positive tumor markers as the prognostic factors for early stage HCC within the Milan criteria. METHODS This study investigated 199 patients who underwent hepatectomy for HCC within the Milan criteria between January 2001 and May 2009. Cumulative recurrence-free survival (RFS), overall survival (OS) and clinicopathological parameters were analyzed according to the number of positive tumor markers. RESULTS In patients with triple positive tumor markers, 5-year RFS and OS was poor (17.1 and 61.4%, respectively). Multivariate analyses revealed independent risk factors for recurrence to be hepatitis C virus antibody positivity, non-initial treatment for HCC and triple positive tumor markers, and the independent risk factors for OS were high indocyanine green retention rate at 15 min value, maximum tumor size and triple positive tumor markers. Pathologically invasive growth, microvascular invasion and moderate to poor differentiation were significantly related to the number of the three tumor markers. CONCLUSION Triple positive tumor markers for early stage HCC within the Milan criteria showed poor prognosis and malignant characteristics. These markers could be a useful predictor for the degree of malignant potential in early stage HCC.
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Affiliation(s)
- Shigeki Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
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Kornberg A. Liver Transplantation for Hepatocellular Carcinoma beyond Milan Criteria: Multidisciplinary Approach to Improve Outcome. ISRN HEPATOLOGY 2014; 2014:706945. [PMID: 27335840 PMCID: PMC4890913 DOI: 10.1155/2014/706945] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/15/2013] [Accepted: 01/03/2014] [Indexed: 12/12/2022]
Abstract
The implementation of the Milan criteria (MC) in 1996 has dramatically improved prognosis after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Liver transplantation has, thereby, become the standard therapy for patients with "early-stage" HCC on liver cirrhosis. The MC were consequently adopted by United Network of Organ Sharing (UNOS) and Eurotransplant for prioritization of patients with HCC. Recent advancements in the knowledge about tumor biology, radiographic imaging techniques, locoregional interventional treatments, and immunosuppressive medications have raised a critical discussion, if the MC might be too restrictive and unjustified keeping away many patients from potentially curative LT. Numerous transplant groups have, therefore, increasingly focussed on a stepwise expansion of selection criteria, mainly based on tumor macromorphology, such as size and number of HCC nodules. Against the background of a dramatic shortage of donor organs, however, simple expansion of tumor macromorphology may not be appropriate to create a safe extended criteria system. In contrast, rather the implementation of reliable prognostic parameters of tumor biology into selection process prior to LT is mandatory. Furthermore, a multidisciplinary approach of pre-, peri-, and posttransplant modulating of the tumor and/or the patient has to be established for improving prognosis in this special subset of patients.
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Affiliation(s)
- A. Kornberg
- Department of Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaningerstraße 22, D-81675 Munich, Germany
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Long-term outcomes after curative resection for patients with macroscopically solitary hepatocellular carcinoma without macrovascular invasion and an analysis of prognostic factors. Med Oncol 2013; 30:696. [PMID: 23975633 DOI: 10.1007/s12032-013-0696-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2013] [Accepted: 08/09/2013] [Indexed: 12/22/2022]
Abstract
The long-term outcome and prognostic factors after curative in patients with single hepatocellular carcinoma (HCC) without macrovascular invasion are still unclear. The objective of this study is to evaluate the effect of curative resection on survival and analyze the prognostic clinicopathologic factors, especially the presence of microvascular invasion (MVI), in these patients. Two hundred and sixty consecutive patients with single HCC without macrovascular invasion who underwent curative resection from December 2004 to December 2007 were retrospectively reviewed in this study. Survival rates were calculated by using the Kaplan-Meier method. Univariate and multivariate analyses of 14 clinicopathologic factors were performed to determine the significant prognostic factors. No patient died within 1 month after the operation. The 1-, 3-, and 5-year overall survival rates after curative resection were 96.54, 83.46, and 74.01%, respectively. Multivariate analysis revealed that only the presence of MVI was an independent negative prognostic factor affecting overall survival. The 1-, 3-, and 5-year disease-free survival rates were 79.62, 62.69, and 56.01%, respectively. The presence of MVI was the only independent unfavorable prognostic factor for disease-free survival. According to our analysis, patients with single HCC without macrovascular invasion after curative resection can be expected to have considerable long-term survival. The presence of MVI was an independent negative prognostic factor for both overall survival and disease-free survival. To improve the prognosis, these patients should be followed up more carefully and might be good candidates for adjuvant therapy.
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Sakamoto N. NX-PVKA assay, a conventional but refined prognostic biomarker for hepatocellular carcinoma. J Gastroenterol Hepatol 2013; 28:755-6. [PMID: 23614337 DOI: 10.1111/jgh.12138] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/21/2013] [Indexed: 12/09/2022]
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Toyoda H, Kumada T, Tada T, Niinomi T, Ito T, Kaneoka Y, Maeda A. Prognostic significance of a combination of pre- and post-treatment tumor markers for hepatocellular carcinoma curatively treated with hepatectomy. J Hepatol 2012; 57:1251-7. [PMID: 22824818 DOI: 10.1016/j.jhep.2012.07.018] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2012] [Revised: 07/11/2012] [Accepted: 07/11/2012] [Indexed: 01/11/2023]
Abstract
BACKGROUND & AIMS Previous studies reported that the combination of three tumor markers for hepatocellular carcinoma (HCC), alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP), has the ability to discriminate survival among patients with HCC. In those studies, however, the study population included all patients with various treatment modalities, and tumor markers were measured only before treatment. We investigated the prognostic value of a combination of these tumor markers for HCC, measured before and after treatment, on survival and recurrence in patients treated with hepatectomy. METHODS A total of 173 patients who underwent hepatectomy for primary, non-recurrent HCC were analyzed. Tumor characteristics, postoperative survival, and recurrence rates were compared according to the number of elevated tumor markers measured before and after treatment. RESULTS The correlation between the number of elevated tumor markers before treatment and tumor size, rate of portal vein invasion, and tumor differentiation, respectively, was stronger than that between the number of elevated tumor markers after treatment. In contrast, the number of elevated tumor markers after treatment displayed an excellent ability to discriminate post-treatment survival and recurrence rates compared to that before treatment, and was an independent factor associated with survival and recurrence in multivariate analysis. CONCLUSIONS The combination of tumor markers measured after hepatectomy has a better discriminatory ability for postoperative survival and recurrence in HCC patients treated with hepatectomy in comparison to the combination of tumor markers measured before treatment.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan.
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Rodríguez-Perálvarez M, Luong TV, Andreana L, Meyer T, Dhillon AP, Burroughs AK. A Systematic Review of Microvascular Invasion in Hepatocellular Carcinoma: Diagnostic and Prognostic Variability. Ann Surg Oncol 2012; 20:325-39. [DOI: 10.1245/s10434-012-2513-1] [Citation(s) in RCA: 386] [Impact Index Per Article: 29.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2012] [Indexed: 02/07/2023]
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Shim JH, Yoon DL, Han S, Lee YJ, Lee SG, Kim KM, Lim YS, Lee HC, Chung YH, Lee YS. Is serum alpha-fetoprotein useful for predicting recurrence and mortality specific to hepatocellular carcinoma after hepatectomy? A test based on propensity scores and competing risks analysis. Ann Surg Oncol 2012; 19:3687-96. [PMID: 22644512 DOI: 10.1245/s10434-012-2416-1] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2012] [Indexed: 12/19/2022]
Abstract
BACKGROUND Serum alpha-fetoprotein (AFP) is frequently used to predict posthepatectomy outcomes in patients with hepatocellular carcinoma (HCC), but its predictive value is still not established. Therefore, we assessed the prognostic significance of AFP status. METHODS Of 525 patients undergoing curative hepatectomy for HCC, 290 had preoperative AFP levels of ≥20 ng/mL (AFP-positive group) and 235 had AFP levels of <20 ng/mL (AFP-negative group). We compared the 2 groups with respect to time-to-recurrence, using the inverse probability of treatment weighted (IPTW) for the entire cohort and propensity score matching, and the cumulative incidence of HCC-specific mortality using competing risks regression. RESULTS During follow-up (median duration 64 months, range 2-137 months), HCC recurred in 54.9 % of the AFP-negative group and 52.4 % of the AFP-positive group; there was no death without recurrence. After IPTW adjustment, time-to-recurrence did not differ in the 2 groups (hazard ratio [HR] 0.86, 95 % confidence interval [95 % CI] 0.66-1.12; P = 0.28). In a propensity-score matched cohort (152 pairs), time-to-recurrence data were similar to those obtained by IPTW adjustment (HR 0.91, 95 % CI 0.65-1.25; P = 0.55). There was no difference in recurrence pattern (site and stage) or treatment between the 2 groups even after propensity-score matching. The adjusted HR evaluating the impact of AFP positivity on the risk of HCC-specific mortality was 0.77 (95 % CI 0.54-1.08; P = 0.13) A multivariable competing risks analysis also failed to reveal a significant correlation between baseline AFP level and HCC-specific mortality in the AFP-positive group. CONCLUSIONS Preoperative AFP levels are not useful for predicting recurrence or survival endpoints following curative hepatectomy for HCC.
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Affiliation(s)
- Ju Hyun Shim
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
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Qiu JL, Huang PZ, You JH, Zou RH, Wang L, Hong J, Li BK, Zhou K, Yuan YF. LIN28 expression and prognostic value in hepatocellular carcinoma patients who meet the Milan criteria and undergo hepatectomy. CHINESE JOURNAL OF CANCER 2012; 31:223-32. [PMID: 22429493 PMCID: PMC3777525 DOI: 10.5732/cjc.011.10426] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Stem cell marker LIN28, related closely with SOX2 and OCT4, has been studied as a biomarker for the maintainance of pluripotent cells in several malignancies. Our previous study showed that SOX2 and OCT4 were negative predictors for hepatocellular carcinoma (HCC). However, the predictive value of LIN28 in HCC outcome is still undetermined. We hypothesized that LIN28 may also play a role as a biomarker for HCC. To test this hypothesis, we examined the expression of LIN28 in 129 radically resected HCC tissues using reverse transcription-polymerase chain reaction and analyzed the association of LIN28 expression with clinicopathologic features and prognosis. Our study showed that LIN28 was expressed at a higher frequency in tumor tissues than in non-HCC tissues (45.0% vs. 21.7%, P = 0.020). Moreover, LIN28 expression was significantly increased in cases with large tumor size (P = 0.010). Univariate analysis did not reveal a significant correlation between LIN28 expression and overall survival or recurrence-free survival. For HCC patients who met the Milan criteria, stratified analysis revealed shorter overall survival (P = 0.007) and recurrence-free survival (P < 0.001) in those with detectable LIN28 expression compared to those with no detectable LIN28 expression. Furthermore, multivariate analysis revealed that LIN28 was a negative independent predictor for both overall survival (hazard ratio= 7.093, P = 0.017) and recurrence-free survival (hazard ratio=5.518, P = 0.004) in patients who met the Milan criteria. Taken together, our results suggest that LIN28 identifies low-risk and high-risk subsets of HCC patients meeting the Milan criteria who undergo hepatectomy.
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Affiliation(s)
- Ji-Liang Qiu
- State Key Laboratory of Oncology in South China, Guangzhou, Guangdong 510060, PR China
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Alpha-fetoprotein and novel tumor biomarkers as predictors of hepatocellular carcinoma recurrence after surgery: a brilliant star raises again. Int J Hepatol 2012; 2012:893103. [PMID: 22792474 PMCID: PMC3391901 DOI: 10.1155/2012/893103] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2012] [Revised: 05/03/2012] [Accepted: 05/04/2012] [Indexed: 12/16/2022] Open
Abstract
Alpha-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP), and lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) have been developed with the intent to detect hepatocellular carcinoma (HCC) and for the surveillance of at-risk patients. However, at present, none of these tests can be recommended to survey cirrhotic patients at risk for HCC development because of their suboptimal ability for routine clinical practice in HCC diagnosis. Starting from these considerations, these markers have been therefore routinely and successfully used as predictors of survival and HCC recurrence in patients treated with curative intent. All these markers have been largely used as predictors in patients treated with hepatic resection or locoregional therapies, mainly in Eastern countries. In recent studies, AFP has been proposed as predictor of recurrence after liver transplantation and as selector of patients in the waiting list. Use of AFP modification during the waiting list for LT is still under investigation, potentially representing a very interesting tool for patient selection. The development of a new predictive model combining radiological and biological features based on biological markers is strongly required. New genetic markers are continuously discovered, but they are not already fully available in the clinical practice.
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