|
1
|
Li J, Cheng X, Meng Y, Wang M. Comparison of clinical characteristics and outcomes in patients with hepatocellular carcinoma based on serum alpha-fetoprotein status. Eur J Gastroenterol Hepatol 2025; 37:619-626. [PMID: 39976057 DOI: 10.1097/meg.0000000000002933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
BACKGROUND Alpha-fetoprotein (AFP) is the most commonly used and crucial tumor marker in clinical diagnosis and prognosis guidance for hepatocellular carcinoma (HCC). However, approximately 30% of HCC patients do not exhibit abnormal serum AFP levels at the time of diagnosis. This study aims to investigate the clinical characteristics and prognosis differences between AFP-negative and AFP-positive patients with HCC. METHODS Clinical data on patients diagnosed between 2010 and 2015 from the Surveillance, Epidemiology, and End Results Program were collected and analyzed. All patients with HCC were reported as AFP-negative or AFP-positive based on AFP test results. Overall survival (OS) and cancer-specific survival (CSS) were compared between the AFP-negative and AFP-positive patients. Logistic regression analysis and multivariable Cox regression analysis were performed to identify the association of AFP with tumor size, lymph node metastasis, distant metastasis, and CSS. RESULTS Of 7090 patients, 2074 (29.3%) and 5016 (70.7%) were AFP-negative and AFP-positive patients, respectively. The 5-year OS and CSS rates in AFP-negative patients were significantly better than AFP-positive patients (36.4 vs. 20.7% and 46.7 vs. 27.2%, both P < 0.001). Logistic regression analysis revealed that the AFP level was an independent risk factor of tumor size [odds ratio (OR), 1.821; 95% confidence interval (CI), 1.625-2.040; P < 0.001], N stage (OR, 1.922; 95% CI, 1.528-2.417; P < 0.001) and M stage (OR, 2.435; 95% CI, 1.980-2.995; P < 0.001). On multivariable Cox-regression analyses, AFP-positive was associated with decreased CSS (hazard ratio, 1.452; 95% CI, 1.355-1.557; P < 0.001). CONCLUSION Abnormal serum AFP was significantly associated with worse prognosis, larger tumor size, more lymph node metastasis, and distant metastasis. Patients with AFP-positive may need more individualized treatment decision and further optimization of HCC management strategies.
Collapse
Affiliation(s)
- Jing Li
- Department of Radiation Oncology, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, China
| | | | | | | |
Collapse
|
|
2
|
Mazza S, Frigerio C, Alfieri D, Mauro A, Torello Viera F, Scalvini D, Barteselli C, Sgarlata C, Veronese L, Bardone M, Rovedatti L, Agazzi S, Strada E, Pozzi L, Maestri M, Ravetta V, Anderloni A. Prognostic Role of Basal Serum Alpha-Fetoprotein in Patients with Hepatocellular Carcinoma Suitable for Curative Treatment. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:692. [PMID: 38792876 PMCID: PMC11123130 DOI: 10.3390/medicina60050692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 04/07/2024] [Accepted: 04/20/2024] [Indexed: 05/26/2024]
Abstract
Background and Objectives: Serum alpha-fetoprotein (AFP) is a recognized affordable oncological marker in patients with hepatocellular carcinoma (HCC). However, AFP's prognostic role has been assessed mainly after specific treatments, and no unanimously recognized cut-offs have been identified. The aim of this study is to investigate the prognostic role of different basal AFP cut-offs on survival and HCC course. Materials and Methods: In this single-center, retrospective study, all patients newly diagnosed with HCC between January 2009 and December 2021 were prospectively enrolled. Only patients suitable for curative HCC treatments were included in the analyses. Patients were stratified according to AFP cut-offs of 20, 200, 400, and 1000 ng/mL, which were correlated with survival outcomes and clinical parameters. Results: A total of 266 patients were analyzed, with a median follow-up time of 41.5 months. Median overall survival (OS) of all cohort was 43 months. At the multivariate Cox-regression analysis, AFP value ≥ 1000 ng/mL correlated with impaired OS (1-year OS: 67% vs. 88%, 5-year OS: 1% vs. 43%; p = 0.005); other risk factors were tumor dimension ≥ 5 cm (HR 1.73; p = 0.002), Child-Pugh class B-C (HR 1.72; p = 0.002), BCLC stage A (vs. 0) (HR 2.4; p = 0.011), and malignant portal vein thrombosis (HR 2.57; p = 0.007). AFP ≥ 1000 ng/mL was also associated with a reduced recurrence-free survival (HR 2.0; p = 0.038), while starting from AFP ≥ 20 ng/mL, a correlation with development of HCC metastases over time (HR 3.5; p = 0.002) was seen. AFP values ≥ 20 ng/mL significantly correlated with tumor size and higher histological grading; starting from AFP values ≥ 400 ng/mL, a significant correlation with Child-Pugh class B-C and female gender was also observed. Conclusions: Basal AFP correlates with relevant outcomes in patients with HCC. It could help identify patients at a higher risk of worse prognosis who might benefit from personalized surveillance and treatment programs. Prospective studies are needed to confirm these results.
Collapse
Affiliation(s)
- Stefano Mazza
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Chiara Frigerio
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy
| | - Daniele Alfieri
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy
| | - Aurelio Mauro
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Francesca Torello Viera
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Davide Scalvini
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy
| | - Chiara Barteselli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Carmelo Sgarlata
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Letizia Veronese
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Marco Bardone
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Laura Rovedatti
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Simona Agazzi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Elena Strada
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Lodovica Pozzi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Marcello Maestri
- General Surgery I, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Valentina Ravetta
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Andrea Anderloni
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| |
Collapse
|
|
3
|
Mahmud N, Shaked A, Olthoff KM, Goldberg DS. Differences in Posttransplant Hepatocellular Carcinoma Recurrence by Etiology of Liver Disease. Liver Transpl 2019; 25:388-398. [PMID: 30362249 PMCID: PMC6395513 DOI: 10.1002/lt.25363] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Accepted: 10/17/2018] [Indexed: 01/10/2023]
Abstract
The 5-year incidence of posttransplant hepatocellular carcinoma (HCC) recurrence is 8%-20%. Several studies have evaluated pretransplant risk factors for HCC recurrence, but nearly all data have treated HCC as a homogeneous condition across all etiologies of liver disease despite differences in tumor biology and baseline incidence of HCC. We sought to evaluate the impact of etiology of liver disease, maximum pretransplant alpha-fetoprotein (AFP), and the interaction of the 2 factors on the risk of HCC recurrence. We performed a retrospective cohort study of HCC transplant recipients using United Network for Organ Sharing (UNOS) data from 2002 to 2016. A competing risks regression was performed to identify variables associated with HCC recurrence and an interaction term between etiology and maximum AFP category. Among 18,406 recipients, 1484 patients experienced HCC recurrence over 3.1 years of median follow-up time. There was a significant interaction between AFP category and etiology of liver disease (P < 0.001). Among patients with a maximum AFP <100 ng/mL, those with alcoholic liver disease had the lowest risk of recurrence. In contrast, in patients with a maximum AFP of 100-499, 500-1000, or >1000 ng/mL, those with alcoholic liver disease had the highest risk of HCC recurrence among all etiologies. In conclusion, risk of HCC recurrence differs by etiology of liver disease, and the significance of elevated pretransplant AFP varies by etiology. Patients with alcoholic liver disease and elevated maximum AFP are at a uniquely high risk of HCC recurrence. These findings have potential UNOS policy implications because the transplant selection process may ultimately benefit from etiology-specific criteria.
Collapse
Affiliation(s)
- Nadim Mahmud
- Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Abraham Shaked
- Division of Transplant Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Kim M Olthoff
- Division of Transplant Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - David S Goldberg
- Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| |
Collapse
|
|
4
|
Abstract
Pedunculated hepatocellular carcinoma is an unusual form of hepatocellular carcinoma protruding from the liver with or without a pedicle. We present a case of pedunculated hepatocellular carcinoma misdiagnosed as right adrenal tumor on MRI and FDG PET/CT. Intraoperative exploration revealed the mass was attached to the liver, but the right adrenal gland was intact. Laparoscopic biopsy revealed poorly differentiated hepatocellular carcinoma. This case indicates it may be difficult to diagnose pedunculated hepatocellular carcinoma because it is hard to define its origin on imaging. Elevated alpha-fetoprotein level and a history of viral hepatitis may be helpful for the diagnosis.
Collapse
|
|
5
|
Donato F, Rodella S, Chiesa R, Picoco C, Donati LF, Nardi G. Diagnostic Accuracy of Primary Liver Cancer: Implications for Cancer Registration. TUMORI JOURNAL 2018; 81:86-90. [PMID: 7778224 DOI: 10.1177/030089169508100203] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Aims and background We evaluated some standardized criteria for classifying incident cases of liver cancer into either primary liver cancer (PLC) or unspecified liver cancer (ULC) on the basis of the diagnostic examinations performed and their results. Methods A pilot hospital-based study (98 cases) was carried out in Verona, northern Italy, with the main aim of assessing the feasibility of the method. The same procedures were subsequently applied in a population-based study (349 cases) in Brescia, northern Italy. Results Diagnosis was made on histologic data in 38.7% and 41.8% of the hospital based and population-based studies, respectively, with a wide variation among different hospitals. The percentage of cases classified as PLC was 78.6% in the hospital-based study and 78.8% in the population-based study. No differences in the proportion of cases attributed to PLC were found according to patients’ age and sex or hospital of admission. The repeatibility of the procedure was assessed by a cross-panel review of 198 cases, and concordance was found in 91.9% of them. Conclusions An operational method for case definition of PLC based on the results of the diagnostic examinations currently performed and some suggestions for cancer registration are proposed.
Collapse
Affiliation(s)
- F Donato
- Cattedra di Igiene, Università di Brescia, Italy
| | | | | | | | | | | |
Collapse
|
|
6
|
Wang F, Liu H, Wang F, Xu R, Wang P, Tang F, Zhang X, Zhu Z, Lv H, Han T. Propranolol suppresses the proliferation and induces the apoptosis of liver cancer cells. Mol Med Rep 2018; 17:5213-5221. [PMID: 29393410 PMCID: PMC5865987 DOI: 10.3892/mmr.2018.8476] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2017] [Accepted: 12/13/2017] [Indexed: 12/26/2022] Open
Abstract
An increasing amount of evidence indicates that the inhibition of β adrenergic signaling can result in the inhibition of tumor growth. However, the role of propranolol in liver cancer and the underlying mechanism remain to be elucidated. The present study aimed to investigate the role of propranolol in liver cancer cell lines and provide evidence for further clinical study. Propranolol was added at different concentrations to HepG2 and HepG2.2.15 liver cancer cells and HL-7702 normal human liver cells. The proliferation of the cell lines was monitored by live-cell imaging at a range of time intervals. Immunofluorescence using DAPI and Hoechst 33342/propidium iodide (PI) staining, Annexin V-FITC/PI double-staining flow cytometry, western blotting and reverse transcription-quantitative polymerase chain reaction were used to investigate the effect of propranolol on liver cancer cell apoptosis. The proliferation of HepG2 and HepG2.2.15 cells was inhibited by 40 and 80 µmol/l propranolol. However, the proliferation of HL-7702 cells was not affected by <160 µmol/l propranolol. Propranolol treatment decreased the expression of adrenergic receptor β-2 to a greater extent than adrenergic receptor β-1, and induced apoptosis in the liver cancer cells. The apoptotic rates of HepG2 and HepG2.2.15 cells increased following treatment with propranolol, while the apoptotic rate of HL-7702 cells was not affected. Propranolol promoted poly (ADP-ribose) polymerase cleavage and decreased the expression of full-length caspase-3 in liver cancer cell lines; it induced S-phase arrest in HepG2 and HepG2.2.15 cell lines, while HL-7702 cells were arrested at the G0/G1 phase of the cell cycle. Thus, it was demonstrated that propranolol inhibited proliferation, promoted apoptosis and induced S-phase arrest in HepG2 and HepG2.2.15 cells.
Collapse
Affiliation(s)
- Fang Wang
- The Third Central Clinical College of Tianjin Medical University, Tianjin 300170, P.R. China
| | - Hui Liu
- Tianjin Institute of Hepatobiliary Disease, Tianjin 300170, P.R. China
| | - Fengmei Wang
- Department of Gastroenterology and Hepatology of Tianjin Third Central Hospital, Tianjin 300170, P.R. China
| | - Ruicheng Xu
- Tianjin Key Laboratory for Biomarkers of Occupational and Environmental Hazard, Tianjin 300170, P.R. China
| | - Peng Wang
- Tianjin Institute of Hepatobiliary Disease, Tianjin 300170, P.R. China
| | - Fei Tang
- Department of Gastroenterology and Hepatology of Tianjin Third Central Hospital, Tianjin 300170, P.R. China
| | - Xu Zhang
- Department of Gastroenterology and Hepatology of Tianjin Third Central Hospital, Tianjin 300170, P.R. China
| | - Zhengyan Zhu
- Tianjin Institute of Hepatobiliary Disease, Tianjin 300170, P.R. China
| | - Hongmin Lv
- Department of Gastroenterology and Hepatology of Tianjin Third Central Hospital, Tianjin 300170, P.R. China
| | - Tao Han
- Department of Gastroenterology and Hepatology of Tianjin Third Central Hospital, Tianjin 300170, P.R. China
| |
Collapse
|
|
7
|
Chaminda SR, Suchintha T, Anuk NM, Supun DA, Bhagya GM, Habarakada LCA, Janaka DSH. Pre-treatment alphafeto protein in hepatocellular carcinoma with non-viral aetiology - a prospective study. BMC Gastroenterol 2017; 17:142. [PMID: 29207969 PMCID: PMC5718018 DOI: 10.1186/s12876-017-0710-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Accepted: 11/27/2017] [Indexed: 12/11/2022] Open
Abstract
Background Alpha-fetoprotein (AFP) is a biomarker for hepatocellular carcinoma (HCC). The significance of pre-treatment AFP (pt-AFP) in non-viral HCC (nvHCC) is not clear. Methods Patients with nvHCC, referred to a Hepatobiliary Clinic from September 2011–2015 were screened. HCC was diagnosed using American Association for the Study of Liver Disease guidelines, and TNM staged. nvHCC was diagnosed when HBsAg and anti-HCVAb was negative. Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores were calculated. AFP level was evaluated against patient characteristics, tumour characteristics and survival. Results Three hundred eighty-nine patients with nvHCC [age 64(12–88) years; 344(88.4%) males] were screened. Median AFP was 25.46 ng/ml (1.16–100,000). 41.2% (n = 160) Of patients had normal AFP level. 22.9% (n = 89) had AFP over 400 ng/ml. Female gender (P < 0.05), vascular invasion (P < 0.001), tumours over 5 cm (P < 0.05), late TNM stage (P < 0.001) and non-surgical candidates had higher AFP levels. Diffuse type (P < 0.001), macro vascular invasion (P < 0.001) and late stage tumours (P < 0.001) had AFP over 400 ng/ml. Having AFP below 400 ng/ml was associated with longer survival (16 vs. 7 months, P < 0.001). Conclusion Pre treatment AFP has a limited value In diagnosing nvHCC, Having a AFP value over 400 ng/ml was associated with aggressive tumour behaviour and poor prognosis.
Collapse
Affiliation(s)
| | - Thilakarathne Suchintha
- Department of surgery, Faculty of Medicine, University of Kelaniya Sri Lanka, Kelaniya, Sri Lanka
| | - Niriella Madunil Anuk
- Department of medicine, Faculty of Medicine, University of Kelaniya Sri Lanka, Kelaniya, Sri Lanka
| | | | - Gunathilake Mahen Bhagya
- Department of surgery, Faculty of Medicine, University of Kelaniya Sri Lanka, Kelaniya, Sri Lanka
| | | | | |
Collapse
|
|
8
|
Wang T, Zhang KH, Hu PP, Wan QS, Han FL, Zhou JM, Huang DQ, Lv NH. Combination of dual serum fluorescence, AFP and hepatic function tests is valuable to identify HCC in AFP-elevated liver diseases. Oncotarget 2017; 8:97758-97768. [PMID: 29228649 PMCID: PMC5716689 DOI: 10.18632/oncotarget.22050] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2017] [Accepted: 10/03/2017] [Indexed: 12/18/2022] Open
Abstract
Serum alpha-fetoprotein (AFP) levels elevated in benign liver diseases (BLD) represent a challenge in hepatocellular carcinoma (HCC) diagnosis. The present study aimed to develop a simple method to identify HCC in AFP-elevated liver diseases based on combining serum fluorescence and general clinical data. Serum specimens and clinical data were collected from 201 HCC and 117 BLD (41 liver cirrhosis, 76 chronic hepatitis) patients with abnormal serum AFP levels. Dual serum fluorescence (autofluorescence and cell-free DNA-related fluorescence) intensities were sequentially measured and expressed as 6 fluorescence indicators. The diagnostic value of these fluorescence and clinical data were evaluated alone and in combination by the area under receiver operating characteristic curve (AUROC). All fluorescence indicators significantly differed between HCC and BLD and some of them were more valuable for diagnosing HCC than AFP (AUROC 0.782-0.801 vs. 0.752). The diagnostic model established with fluorescence indicators, AFP, hepatic function tests and age showed that AUROC, sensitivity, specificity and accuracy were 0.958 (95% CI 0.936-0.979), 92.0%, 88.9% and 92.3%, respectively, and positive rates in AFP-negative, early and small HCCs were 73.8%, 81.6% and 74.3%, respectively. In conclusion, the combination of dual serum fluorescence, AFP, hepatic function tests and age is simple and valuable for identifying HCC in serum AFP-elevated liver diseases.
Collapse
Affiliation(s)
- Ting Wang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Jiangxi Institute of Gastroenterology and Hepatology, Nanchang 330006, China
| | - Kun-He Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Jiangxi Institute of Gastroenterology and Hepatology, Nanchang 330006, China
| | - Piao-Ping Hu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Jiangxi Institute of Gastroenterology and Hepatology, Nanchang 330006, China
| | - Qin-Si Wan
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Jiangxi Institute of Gastroenterology and Hepatology, Nanchang 330006, China
| | - Fang-Li Han
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Jiangxi Institute of Gastroenterology and Hepatology, Nanchang 330006, China
| | - Jian-Ming Zhou
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Jiangxi Institute of Gastroenterology and Hepatology, Nanchang 330006, China
| | - De-Qiang Huang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Jiangxi Institute of Gastroenterology and Hepatology, Nanchang 330006, China
| | - Nong-Hua Lv
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Jiangxi Institute of Gastroenterology and Hepatology, Nanchang 330006, China
| |
Collapse
|
|
9
|
Higher Ratio of Serum Alpha-Fetoprotein Could Predict Outcomes in Patients with Hepatitis B Virus-Associated Hepatocellular Carcinoma and Normal Alanine Aminotransferase. PLoS One 2016; 11:e0157299. [PMID: 27304617 PMCID: PMC4909194 DOI: 10.1371/journal.pone.0157299] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2016] [Accepted: 05/26/2016] [Indexed: 12/14/2022] Open
Abstract
Background The role of serum alpha-fetoprotein (AFP) levels in the surveillance and diagnosis of hepatocellular carcinoma (HCC) is controversial. The aim of this study was to investigate the value of serially measured serum AFP levels in HCC progression or recurrence after initial treatment. Methods A total of 722 consecutive patients newly diagnosed with HCC and treated at the National Cancer Center, Korea, between January 2004 and December 2009 were enrolled. The AFP ratios between 4–8 weeks post-treatment and those at the time of HCC progression or recurrence were obtained. Multivariate logistic regression analysis was performed to correlate the post-treatment AFP ratios with the presence of HCC progression or recurrence. Results The etiology of HCC was related to chronic hepatitis B virus (HBV) infection in 562 patients (77.8%), chronic hepatitis C virus (HCV) infection in 74 (10.2%), and non-viral cause in 86 (11.9%). There was a significant decrease in serum AFP levels from the baseline to 4 to 8 weeks after treatment (median AFP, 319.6 ng/mL vs. 49.6 ng/mL; p< 0.001). Multivariate analysis showed that an AFP ratio > 1.0 was an independently associated with HCC progression or recurrence. Among the different causes of HCC analyzed, this association was significant only for HCC related to chronic hepatitis B (p< 0.001) and non-viral causes (p<0.05), and limited only to patients who had normal alanine aminotransferase (ALT) levels. Conclusion Serial measurements of serum AFP ratios could be helpful in detecting progression or recurrence in treated patients with HBV-HCC and normal ALT.
Collapse
|
|
10
|
Abdel-Hamid NM, Abouzied MM, Nazmy MH, Fawzy MA, Gerges AS. A suggested guiding panel of seromarkers for efficient discrimination between primary and secondary human hepatocarcinoma. Tumour Biol 2016; 37:2539-2546. [DOI: 10.1007/s13277-015-4025-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2015] [Accepted: 08/31/2015] [Indexed: 12/25/2022] Open
|
|
11
|
Abouzied MM, Eltahir HM, Fawzy MA, Abdel-Hamid NM, Gerges AS, El-Ibiari HM, Nazmy MH. Estimation of leucine aminopeptidase and 5-nucleotidase increases alpha-fetoprotein sensitivity in human hepatocellular carcinoma cases. Asian Pac J Cancer Prev 2015; 16:959-63. [PMID: 25735389 DOI: 10.7314/apjcp.2015.16.3.959] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
PURPOSE To find parameters that can increase alpha-fetoprotein (AFP) sensitivity and so help in accurate diagnosis and rapid management of hepatocullular carcinoma (HCC), as AFP has limited utility of distinguishing HCC from benign hepatic disorders for its high false-positive and false negative rates. MATERIALS AND METHODS Serum levels of AFP, 5'-nucleotidase enzyme activity (5-NU) and leucine aminopeptidase enzyme (LAP) activity were measured in 40 individuals. RESULTS LAP and 5'NU were elevated in HCC at p<0.001. Pearson correlation coefficients showed that changes in AFP exhibited positive correlation with both 5'-NU and LAP at (p<0.001). The complementary use of LAP only with AFP resulted in an increase in sensitivity of AFP from 75% to 90% in detecting HCC. The complementary use of both LAP and 5-NU with AFP resulted in an increased sensitivity of AFP in detecting HCC from 75% to 95%. CONCLUSIONS LAP and 5-FU can be determined in HCC patients in combination with AFP to improve its sensitivity and decrease false negative results.
Collapse
Affiliation(s)
- Mekky Mohammed Abouzied
- Departments of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Medina, Kingdom of Saudi Arabia E-mail :
| | | | | | | | | | | | | |
Collapse
|
|
12
|
Mazzoccoli G, Tarquini R, Valoriani A, Oben J, Vinciguerra M, Marra F. Management strategies for hepatocellular carcinoma: old certainties and new realities. Clin Exp Med 2015; 16:243-56. [PMID: 26077653 DOI: 10.1007/s10238-015-0368-z] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Accepted: 06/04/2015] [Indexed: 12/18/2022]
Abstract
Hepatocellular carcinoma (HCC) is a highly prevalent disease ranking among the ten most common cancers worldwide with increasing trend of incidence in most developed countries. The great healthcare costs and economic burden of HCC dictate proper preventive interventions as well as surveillance and screening programs to decrease disease incidence and allow early diagnosis. HCC treatment outcomes are affected by several variables, including liver function, patient's performance status, and tumor stage. In line with the Barcelona Clinic Liver Cancer (BCLC) staging curative treatments, such as surgery or radio-frequency ablation, are indicated in early-stage HCC (BCLC-A), and the noncurative treatments are indicated in intermediate and advanced stages of HCC (BCLC-B, C). Transarterial chemoembolization (TACE) represents the treatment of choice for intermediate-stage HCC with Child-Pugh A cirrhosis, and the long-term survival after liver transplantation is inferior to that of early-stage HCCs. In advanced-stage HCC or when complete necrosis is not achieved or early recurrence after TACE develops, individualized treatments such as systemic treatment or combined radiation therapy are indicated. The increasing knowledge of the genomic landscape of HCC and the development of molecular-targeted therapies is heading toward expanding the armamentarium for HCC management.
Collapse
Affiliation(s)
- Gianluigi Mazzoccoli
- Department of Medical Sciences, Division of Internal Medicine and Chronobiology Unit, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
| | - Roberto Tarquini
- Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy.,Inter-company Department for Continuity Assistance, School of Medicine, University of Florence, Florence, Italy.,San Giuseppe Hospital, Empoli, Italy
| | - Alice Valoriani
- Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy.,Inter-company Department for Continuity Assistance, School of Medicine, University of Florence, Florence, Italy.,San Giuseppe Hospital, Empoli, Italy
| | - Jude Oben
- University College London (UCL) - Institute for Liver and Digestive Health, Division of Medicine, Royal Free Hospital, London, UK
| | - Manlio Vinciguerra
- University College London (UCL) - Institute for Liver and Digestive Health, Division of Medicine, Royal Free Hospital, London, UK.,Istituto EuroMEditerraneo di Scienza e Tecnologia (IEMEST), Palermo, Italy.,School of Science and Technology, Nottingham Trent University, Nottingham, UK
| | - Fabio Marra
- Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy
| |
Collapse
|
|
13
|
Chan SL, Mo F, Johnson PJ, Siu DYW, Chan MHM, Lau WY, Lai PBS, Lam CWK, Yeo W, Yu SCH. Performance of serum α-fetoprotein levels in the diagnosis of hepatocellular carcinoma in patients with a hepatic mass. HPB (Oxford) 2014; 16:366-372. [PMID: 23980880 PMCID: PMC3967889 DOI: 10.1111/hpb.12146] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2013] [Accepted: 05/20/2013] [Indexed: 12/12/2022]
Abstract
OBJECTIVES The role of serum α-fetoprotein (AFP) measurements in the diagnosis of hepatocellular carcinoma (HCC) remains controversial. Some guidelines have advised against the use of AFP in the diagnosis of HCC. This study was conducted to evaluate the performance of AFP in the diagnosis of HCC, and to identify the optimal cut-off value of serum AFP in the diagnosis of HCC in patients with a hepatic mass. METHODS Patients who presented during the period from May 1997 to March 2003 with hepatic lesions, for whom paired data on serum AFP values at baseline and lesion histology were available, were reviewed. The performance of AFP in the diagnosis of HCC was determined using receiver operating characteristic curve analysis. RESULTS Data for a total of 805 patients were evaluated. The mean AFP value was 26,900 ng/ml (range: 0-1,965,461 ng/ml). The histological diagnosis was HCC in 557 patients. The optimal AFP cut-off value was 10 ng/ml (for sensitivity of 82.6% and specificity of 70.4%). At a cut-off level of 200 ng/ml, sensitivity, specificity, and positive and negative predictive values were 47.7%, 97.1%, 97.5% and 44.4%, respectively. The diagnostic performance of AFP remains similar in patients with chronic hepatitis B virus infection, despite a lower negative predictive value. Common aetiologies of liver lesions associated with elevated AFP include cholangiocarcinoma and neuroendocrine tumours. CONCLUSIONS In Asian patients with suspicious liver lesions, the cut-off AFP level of 200 ng/ml is useful to achieve a diagnosis of HCC with high specificity and reasonable sensitivity. The measurement of serum AFP should not be excluded from guidelines for the diagnosis of HCC.
Collapse
Affiliation(s)
- Stephen L Chan
- State Key Laboratory in Oncology in South China, Sir Y. K. Pao Centre for Cancer, Department of Clinical Oncology, Hong Kong Cancer InstituteHong Kong, China
| | - Frankie Mo
- State Key Laboratory in Oncology in South China, Sir Y. K. Pao Centre for Cancer, Department of Clinical Oncology, Hong Kong Cancer InstituteHong Kong, China
| | - Philip J Johnson
- Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of LiverpoolLiverpool, UK
| | - Deyond Y W Siu
- Department of Vascular and Interventional Radiology Foundation Clinical Science Center, Chinese University of Hong KongHong Kong, China
| | - Michael H M Chan
- Department of Chemical Pathology, Chinese University of Hong KongHong Kong, China
| | - Wan Y Lau
- Department of Faculty of Medicine, Chinese University of Hong KongHong Kong, China
| | - Paul B S Lai
- Department of Surgery, Prince of Wales Hospital, Chinese University of Hong KongHong Kong, China
| | - Christopher W K Lam
- Department of Chemical Pathology, Chinese University of Hong KongHong Kong, China
| | - Winnie Yeo
- State Key Laboratory in Oncology in South China, Sir Y. K. Pao Centre for Cancer, Department of Clinical Oncology, Hong Kong Cancer InstituteHong Kong, China
| | - Simon C H Yu
- Department of Vascular and Interventional Radiology Foundation Clinical Science Center, Chinese University of Hong KongHong Kong, China
| |
Collapse
|
|
14
|
Wong GLH, Chan HLY, Tse YK, Chan HY, Tse CH, Lo AOS, Wong VWS. On-treatment alpha-fetoprotein is a specific tumor marker for hepatocellular carcinoma in patients with chronic hepatitis B receiving entecavir. Hepatology 2014; 59:986-95. [PMID: 24123097 DOI: 10.1002/hep.26739] [Citation(s) in RCA: 106] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2013] [Accepted: 09/08/2013] [Indexed: 12/13/2022]
Abstract
UNLABELLED Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) surveillance, which is criticized as neither sensitive nor specific in active hepatitis and liver cirrhosis. The aim of this study was to determine the performance of AFP as a tumor marker for HCC in entecavir-treated patients with chronic hepatitis B (CHB). This was a retrospective-prospective cohort study of 1,531 entecavir-treated patients under regular HCC surveillance with AFP and ultrasonography. Mean age was 52 ± 12 years; 1,099 (72%) patients were male and 332 (21.7%) had clinical evidence of cirrhosis. At a mean follow-up of 51 ± 13 months, 57 (2.9%) patients developed HCC (median size: 3.3 cm). AFP fluctuated with alanine aminotransferase (ALT) and peaked at the time of starting entecavir, then gradually decreased after. AFP started to increase 6 months before the diagnosis of HCC. The receiver operator characteristic curve (AUROC) of AFP was highest at the time of HCC diagnosis (0.85; 95% confidence interval [CI]: 0.73-0.98) and remained satisfactory at 3 (0.82; 95% CI: 0.73-0.91) and 6 months (0.79; 95% CI: 0.69-0.89) before the diagnosis. Using the conventional AFP cut-off (20 μg/L) at month 0, the sensitivity and specificity to diagnose HCC were 38.6% and 98.9%, respectively. Adopting the lower cut-off value (6 μg/L) of AFP level at month 0, sensitivity was increased to 80.7%, whereas specificity was decreased to 80.4%. CONCLUSION On-treatment AFP is a specific tumor marker for HCC in CHB patients receiving entecavir therapy. Adopting a lower cut-off value of AFP level at 6 μg/L would significantly increase the sensitivity for HCC detection.
Collapse
Affiliation(s)
- Grace L H Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | | | | | | | | | | | | |
Collapse
|
|
15
|
Xiao J, Zhao Y, Varghese RS, Zhou B, Di Poto C, Zhang L, Tadesse MG, Ziada DH, Shetty K, Ressom HW. Evaluation of metabolite biomarkers for hepatocellular carcinoma through stratified analysis by gender, race, and alcoholic cirrhosis. Cancer Epidemiol Biomarkers Prev 2013; 23:64-72. [PMID: 24186894 DOI: 10.1158/1055-9965.epi-13-0327] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND The effects of hepatocellular carcinoma on liver metabolism and circulating metabolites have been subjected to continuing investigation. This study compares the levels of selected metabolites in sera of hepatocellular carcinoma cases versus patients with liver cirrhosis and evaluates the influence of gender, race, and alcoholic cirrhosis on the performance of the metabolites as candidate biomarkers for hepatocellular carcinoma. METHODS Targeted quantitation of 15 metabolites is performed by selected research monitoring in sera from 89 Egyptian subjects (40 hepatocellular carcinoma cases and 49 cirrhotic controls) and 110 U.S. subjects (56 hepatocellular carcinoma cases and 54 cirrhotic controls). Logistic regression models are used to evaluate the ability of these metabolites in distinguishing hepatocellular carcinoma cases from cirrhotic controls. The influences of gender, race, and alcoholic cirrhosis on the performance of the metabolites are analyzed by stratified logistic regression. RESULTS Two metabolites are selected on the basis of their significance to both cohorts. Although both metabolites discriminate hepatocellular carcinoma cases from cirrhotic controls in males and Caucasians, they are insignificant in females and African Americans. One metabolite is significant in patients with alcoholic cirrhosis and the other in nonalcoholic cirrhosis. CONCLUSIONS The study demonstrates the potential of two metabolites as candidate biomarkers for hepatocellular carcinoma by combining them with α-fetoprotein (AFP) and gender. Stratified statistical analyses reveal that gender, race, and alcoholic cirrhosis affect the relative levels of small molecules in serum. IMPACT The findings of this study contribute to a better understanding of the influence of gender, race, and alcoholic cirrhosis in investigating small molecules as biomarkers for hepatocellular carcinoma.
Collapse
Affiliation(s)
- Junfeng Xiao
- Authors' Affiliations: Department of Oncology, Lombardi Comprehensive Cancer Center and Georgetown University Medical Center; Department of Mathematics and Statistics, Georgetown University; MedStar Georgetown University Hospital and Georgetown University Medical Center, Washington, District of Columbia; and Department of Tropical Medicine and Infectious Diseases, Tanta Faculty of Medicine, Tanta University, Tanta, Egypt
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
16
|
Predisposing factors of hepatocellular carcinoma recurrence following complete remission in response to transarterial chemoembolization. Dig Dis Sci 2013; 58:1758-65. [PMID: 23361574 DOI: 10.1007/s10620-013-2562-8] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2012] [Accepted: 01/02/2013] [Indexed: 12/31/2022]
Abstract
BACKGROUND AND AIM The aim of our study was to determine the predictors of recurrences in hepatocellular carcinoma (HCC) patients who had achieved complete remission (CR) by transarterial chemoembolization (TACE). METHODS A total of 220 consecutive HCC patients who had achieved CR by TACE were followed for a median 72 months. CR was defined as complete lipiodol uptake based on the results of lipiodol-computed tomography 4 weeks after TACE and no additional tumor staining on the follow-up angiography. Recurrence patterns were classified as local recurrence and secondary tumor, respectively, in relation to the location of recurrence; early and late recurrence were classified in relation to recurrence time. RESULTS Recurrence of HCC was observed in 169 patients (77 %), of whom 91 (54 %) had local recurrences, 61 (36 %) had secondary tumor, and 17 (10 %) had both. There were 45 (27 %) early and 124 (73 %) late recurrences. Local recurrence developed more frequently in patients with early recurrence than in those with late recurrence (62 vs. 51 %, respectively), while secondary tumor was detected more commonly in patients with late recurrence than in those with early recurrence (39 vs. 29 %, respectively; P < 0.001). In multivariate analyses, multinodularity [hazard ratio (HR) 2.351, P = 0.023] and a persistently high serum alpha-fetoprotein level following CR (HR 3.173, P < 0.001) were significant predictors of early recurrence. Older age (≥ 60 years; HR 1.531, P = 0.043), advanced Child-Pugh class (HR 1.983, P = 0.002), and the association with cirrhosis (HR 1.756, P = 0.028) were predictors of late recurrence following CR. CONCLUSIONS Early recurrences following CR by TACE may be due mainly to undetectable remaining tumors, whereas late recurrences may be caused by newly appearing tumors in patients with a background of advanced cirrhotic liver.
Collapse
|
|
17
|
Patel RB, Gupta NR, Vasava NC, Khambholja JR, Chauhan S, Desai A. Situs Inversus Totalis (SIT) with Hepatocellular Carcinoma (HCC): A Rare Case Report and Review of 12 Other Cases. Indian J Surg 2012; 75:424-9. [PMID: 24465096 DOI: 10.1007/s12262-012-0744-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2012] [Accepted: 09/03/2012] [Indexed: 12/21/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the seventh-most common malignancy in males and ninth in females with incidence of one million new cases every year. Situs inversus totalis (SIT) is a rare congenital condition, in which there is a mirror-image transposition of both the abdominal and thoracic viscera. There are very few reported cases of HCC developing in people with SIT. In this review, we present a new case of HCC with SIT, and a review of literatures published between 1983 and 2011 on it. The literatures in English were searched through PubMed and Google Scholar, while those in Japanese language were accessed through J-EAST and translated in English with the help of Google translator on 22 April 2012. There are 6 English and 6 Japanese literatures showing 12 published cases, of which 10 cases were from Japan, 1 from Taiwan and 1 from China. Our case is probably the first case in the world beyond these regions. The articles containing adequate information, such as patient age and sex, investigations, diagnosis, type of congenital anomalies and methods of surgery, were reviewed. On reviewing the literature, we observed that clinical manifestations, laboratory findings and etiology correlate well with HCC, while anomalous hepatic vascularity correlates well with SIT. The reason for high incidence of HCC with SIT in Japan is not well correlated, but may be explained by higher incidence of SIT. All varieties of hepatic resection were feasible in cases of SIT.
Collapse
Affiliation(s)
- Rajan B Patel
- Department of Surgery, Smt. NHL Municipal Medical College, Ahmadabad, India 380014 ; 106, Alkapuri Society, Ghatlodia, Ahmadabad, India 380061
| | - Natvar R Gupta
- Department of Surgery, Smt. NHL Municipal Medical College, Ahmadabad, India 380014
| | - Nitin C Vasava
- Department of Surgery, Smt. NHL Municipal Medical College, Ahmadabad, India 380014
| | - Janak R Khambholja
- Department of Surgery, Smt. NHL Municipal Medical College, Ahmadabad, India 380014
| | - Sanjay Chauhan
- Department of Surgery, Smt. NHL Municipal Medical College, Ahmadabad, India 380014
| | - Amit Desai
- Department of Surgery, Smt. NHL Municipal Medical College, Ahmadabad, India 380014
| |
Collapse
|
|
18
|
Choi KK, Hong YJ, Choi SB, Park YN, Choi JS, Lee WJ, Kim KS. Hepatocellular carcinoma during pregnancy: is hepatocellular carcinoma more aggressive in pregnant patients? JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2011; 18:422-31. [PMID: 21116657 DOI: 10.1007/s00534-010-0345-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND/PURPOSE Hepatocellular carcinoma (HCC) during pregnancy is a very rare condition and is believed to have a worse prognosis than HCC in non-pregnant women. We evaluated the prognosis and the diagnostic and therapeutic strategies for HCC in pregnant women. METHODS We retrospectively analyzed 4 cases in our hospital and 44 cases described in the medical literature since 1957; we also compared the cases reported before 1995 and those reported during/after 1995. RESULTS The overall 6-month and 1-, 2-, and 3-year survival rates in the patients reported in the literature were 50, 29.5, 18.2, and 13.6%, respectively (n = 44). The mean ages at diagnosis before and during/after 1995 were 31.4 ± 7.2 and 28.9 ± 4.4 years, respectively (P = 0.113). The following characteristics were significantly more common in the later group: fewer pregnancies; the absence of advanced signs or symptoms; receipt of therapy; tendency to undergo surgery; and higher 6-month and 1-, 2-, and 3-year survival rates. The median survivals of the groups before and during/after 1995 were 18 and 25.5 months, respectively (P < 0.001). CONCLUSIONS The morbidity and mortality of HCC during pregnancy has improved over time, as diagnoses have tended to be made earlier and patients have tended to receive surgical and other treatments.
Collapse
Affiliation(s)
- Kang Kook Choi
- Kwandong Graduate School of Medicine, Gangneung-si, Gangwon-do, Korea
| | | | | | | | | | | | | |
Collapse
|
|
19
|
Moon YH, Won JH, Moon G, Heo RK, Seung KM, Lee IY, Jang MJ, Kwon SY, Yu DS. The Effect of the Bujeonghangam-tang Extract on Hepatocellular Carcinogenesis and Hepatic Cirrhosis Induced by Diethylnitrosarnine and CCl 4in Rats. J Pharmacopuncture 2010. [DOI: 10.3831/kpi.2010.13.2.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
|
|
20
|
Sturgeon CM, Duffy MJ, Hofmann BR, Lamerz R, Fritsche HA, Gaarenstroom K, Bonfrer J, Ecke TH, Grossman HB, Hayes P, Hoffmann RT, Lerner SP, Löhe F, Louhimo J, Sawczuk I, Taketa K, Diamandis EP. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in liver, bladder, cervical, and gastric cancers. Clin Chem 2010; 56:e1-48. [PMID: 20207771 DOI: 10.1373/clinchem.2009.133124] [Citation(s) in RCA: 139] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Updated National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for the use of tumor markers in the clinic have been developed. METHODS Published reports relevant to use of tumor markers for 4 cancer sites--liver, bladder, cervical, and gastric--were critically reviewed. RESULTS Alpha-fetoprotein (AFP) may be used in conjunction with abdominal ultrasound for early detection of hepatocellular carcinoma (HCC) in patients with chronic hepatitis or cirrhosis associated with hepatitis B or C virus infection. AFP concentrations >200 microg/L in cirrhotic patients with typical hypervascular lesions >2 cm in size are consistent with HCC. After a diagnosis of HCC, posttreatment monitoring with AFP is recommended as an adjunct to imaging, especially in the absence of measurable disease. Although several urine markers have been proposed for bladder cancer, none at present can replace routine cystoscopy and cytology in the management of patients with this malignancy. Some may, however, be used as complementary adjuncts to direct more effective use of clinical procedures. Although carcinoembryonic antigen and CA 19-9 have been proposed for use gastric cancer and squamous cell carcinoma antigen for use in cervical cancer, none of these markers can currently be recommended for routine clinical use. CONCLUSIONS Implementation of these recommendations should encourage optimal use of tumor markers for patients with liver, bladder, cervical, or gastric cancers.
Collapse
Affiliation(s)
- Catharine M Sturgeon
- Department of Clinical Biochemistry, Royal Infirmary of Edinburgh, Edinburgh, UK.
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
21
|
Di Bisceglie AM, Befeler AS. Tumors and Cysts of the Liver. SLEISENGER AND FORDTRAN'S GASTROINTESTINAL AND LIVER DISEASE 2010:1569-1592.e6. [DOI: 10.1016/b978-1-4160-6189-2.00094-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
22
|
Heo RK, Seung KM, Kim SY, Je JT, Kwon SY, Moon G, Lee JD, Won JH. The Effect of the Keughachukeo-tang Extract on the Hepatocellular Carcinogenesis and Acute Liver Damage Induced by Diethylnitrosamine and CCl 4in Rats. J Pharmacopuncture 2009. [DOI: 10.3831/kpi.2009.12.4.063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
|
|
23
|
Lee JB, Heo RK, Seung KM, Moon G, Lee JD, Won JH. The Effect of Injinho-tang Extract on Hepatocellular Carcinogenesis and Hepatic Cirrhosis Induced by Diethylnitrosamine and CCl 4in Rats. J Pharmacopuncture 2009. [DOI: 10.3831/kpi.2009.12.3.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
|
|
24
|
Park JW, An M, Choi JI, Kim YI, Kim SH, Lee WJ, Park SJ, Hong EK, Kim CM. Accuracy of clinical criteria for the diagnosis of hepatocellular carcinoma without biopsy in a Hepatitis B virus-endemic area. J Cancer Res Clin Oncol 2007; 133:937-43. [PMID: 17516087 DOI: 10.1007/s00432-007-0232-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2006] [Accepted: 04/20/2007] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Several sets of criteria have been suggested for clinical diagnosis of hepatocellular carcinoma (HCC) without biopsy but there are no comprehensive data to support the usefulness of these criteria. Here, we sought to validate the accuracy of our clinical criteria for HCC diagnosis in a cohort of patients, and further tested the effect of HBV and clinical cirrhosis status on diagnostic accuracy. METHODS A total of 232 patients with liver nodules >1 cm in diameter who underwent surgical resection or liver biopsy, and had fulfilled all required examinations for clinical non-invasive diagnosis of HCC were reviewed retrospectively. RESULTS Hepatitis B virus (HBV) was positive in 170 patients (73.3%). One hundred and eighty-nine cases were diagnosed as HCC using the clinical criteria and 186 cases of HCC were confirmed by pathologic examination. The overall sensitivity, specificity and positive predictive value of the clinical criteria were 95.1, 73.9 and 93.7%, respectively. The accuracy was not significantly affected by lesion size (1-2 cm vs. >2 cm) or the presence of clinical cirrhosis. The sensitivities were 97.3 and 86.8% in the HBsAg positive group and non-HBV group, respectively (P<0.001), and the specificities were 56.5 and 91.3%, respectively (P<0.001). CONCLUSIONS The clinical criteria for the diagnosis of HCC showed an acceptable accuracy irrespective of lesion size or the presence of clinical cirrhosis in an HBV-endemic population. However, the presence of HBV affected the sensitivity and specificity of the clinical criteria for HCC diagnosis in an HBV endemic area.
Collapse
Affiliation(s)
- Joong-Won Park
- Center for Liver Cancer, National Cancer Center, 809 Madu 1-dong, Ilsan-gu, Goyang, Gyeonggi, 411-769, South Korea.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
25
|
Arrieta O, Cacho B, Morales-Espinosa D, Ruelas-Villavicencio A, Flores-Estrada D, Hernández-Pedro N. The progressive elevation of alpha fetoprotein for the diagnosis of hepatocellular carcinoma in patients with liver cirrhosis. BMC Cancer 2007; 7:28. [PMID: 17288606 PMCID: PMC1803796 DOI: 10.1186/1471-2407-7-28] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2006] [Accepted: 02/08/2007] [Indexed: 02/07/2023] Open
Abstract
Background Hepatocellular carcinoma is the most common cause of primary liver neoplasms and is one of the main causes of death in patients with liver cirrhosis. High Alpha fetoprotein serum levels have been found in 60–70% of patients with Hepatocellular carcinoma; nevertheless, there are other causes that increase this protein. Alpha fetoprotein levels ≥200 and 400 ng/mL in patients with an identifiable liver mass by imaging techniques are diagnostic of hepatocellular carcinoma with high specificity. Methods We analysed the sensitivity and specificity of the progressive increase of the levels of alpha fetoprotein for the detection of hepatocellular carcinoma in patients with liver cirrhosis. Seventy-four patients with cirrhosis without hepatocellular carcinoma and 193 with hepatic lesions diagnosed by biopsy and shown by image scans were included. Sensitivity and specificity of transversal determination of alpha fetoprotein ≥ 200 and 400 ng/mL and monthly progressive elevation of alpha fetoprotein were analysed. Areas under the ROC curves were compared. Positive and negative predictive values adjusted to a 5 and 10% prevalence were calculated. Results For an elevation of alpha fetoprotein ≥ 200 and 400 ng/mL the specificity is of 100% in both cases, with a sensitivity of 36.3 and 20.2%, respectively. For an alpha fetoprotein elevation rate ≥7 ng/mL/month, sensitivity was of 71.4% and specificity of 100%. The area under the ROC curve of the progressive elevation was significantly greater than that of the transversal determination of alpha fetoprotein. The positive and negative predictive values modified to a 10% prevalence are of: 98.8% and 96.92%, respectively; while for a prevalence of 5% they were of 97.4% and 98.52%, respectively. Conclusion The progressive elevation of alpha fetoprotein ≥7 ng/mL/month in patients with liver cirrhosis is useful for the diagnosis of hepatocellular carcinoma in patients that do not reach αFP levels ≥200 ng/mL. Prospective studies are required to confirm this observation.
Collapse
Affiliation(s)
- Oscar Arrieta
- Department of Medical Oncology, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico
- Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
| | - Bernardo Cacho
- Department of Internal Medicine, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" (INCMNSZ), Mexico City, Mexico
| | | | - Ana Ruelas-Villavicencio
- Department of Internal Medicine, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" (INCMNSZ), Mexico City, Mexico
| | - Diana Flores-Estrada
- Department of Medical Oncology, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico
| | - Norma Hernández-Pedro
- Department of Medical Oncology, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico
| |
Collapse
|
|
26
|
Senturk H, Cumali R. Extreme Elevation of Serum Alpha Fetoprotein in Decompensated Cirrhosis without Hcc: an Ominous Sign. Int J Biol Markers 2007. [DOI: 10.1177/172460080702200103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Three cases of extreme elevation of serum alpha fetoprotein (>10,000 ng/mL) with decompensated cirrhosis without demonstrable hepatocellular carcinoma are reported. While 2 patients died of liver failure, 1 survived after liver transplantation. Extreme elevation of alpha fetoprotein not associated with hepatocellular carcinoma in liver cirrhosis heralds an ominous prognosis necessitating urgent liver transplantation.
Collapse
Affiliation(s)
- H. Senturk
- Medicine, Department of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical Faculty, University of Istanbul, Istanbul - Turkey
| | - R. Cumali
- Fellow in Radiology, Section of Radiodiagnostics, Department of Internal Medicine, Cerrahpasa Medical Faculty, University of Istanbul, Istanbul - Turkey
| |
Collapse
|
|
27
|
Abstract
The incidence of hepatocellular carcinoma (HCC) is rising throughout the world. HCC meets the criteria for which a disease benefits from screening or surveillance: it is an important health problem; those with cirrhosis are the targets for surveillance; there is acceptable treatment if diagnosed early; surveillance using alpha-fetoprotein and ultrasound has been shown to be cost effective; surveillance is widely implemented by health care professionals and accepted by patients; standardized recall procedures exists; and the screening tests must achieve an acceptable level of accuracy in the population undergoing screening. The latter point is the main limitation of surveillance for HCC. In this review we will discuss the currently available tests for the surveillance of HCC.
Collapse
Affiliation(s)
- Jorge A Marrero
- Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109-0362, USA.
| |
Collapse
|
|
28
|
Pierens GK, Palframan ME, Tranter CJ, Carroll AR, Quinn RJ. A robust clustering approach for NMR spectra of natural product extracts. MAGNETIC RESONANCE IN CHEMISTRY : MRC 2005; 43:359-365. [PMID: 15747316 DOI: 10.1002/mrc.1562] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
A robust method was developed to cluster similar NMR spectra from partially purified extracts obtained from a range of marine sponges and a plant biota. The NMR data were acquired using microtiter plate NMR (VAST) in protonated solvents. A sample data set which contained several clusters was used to optimize the protocol. The evaluation of the robustness was performed using three different clustering methods: tree clustering analysis, K-means clustering and multidimensional scaling. These methods were compared for consistency using the sample data set and the optimized methodology was applied to clustering of a set of spectra from partially purified biota extracts.
Collapse
Affiliation(s)
- Gregory K Pierens
- Natural Product Discovery, Eskitis Institute, Griffith University, Brisbane, Queensland 4111, Australia
| | | | | | | | | |
Collapse
|
|
29
|
Viruses in the Intensive Care Unit (ICU). TROPICAL AND PARASITIC INFECTIONS IN THE INTENSIVE CARE UNIT 2005. [PMCID: PMC7122063 DOI: 10.1007/0-387-23380-6_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Whereas viruses are not usually considered to be important causes of ICU admission this review has demonstrated this perception to be incorrect. Viruses and their manifestations differ from continent to continent and hemisphere to hemisphere and it is essential that the intensivist be familiar with diagnosis and management of these ubiquitous organisms.
Collapse
|
|
30
|
Jang MK, Lee HC, Kim IS, Lim YS, Chung YH, Lee YS, Sung KB, Yoon HK, Ko GY, Kim AY, Suh DJ. Role of additional angiography and chemoembolization in patients with hepatocellular carcinoma who achieved complete necrosis following transarterial chemoembolization. J Gastroenterol Hepatol 2004; 19:1074-80. [PMID: 15304127 DOI: 10.1111/j.1440-1746.2004.03414.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIMS Although transarterial chemoembolization (TACE) has been reported to have antitumor effects in patients with hepatocellular carcinoma (HCC), optimal time schedules and follow-up methods have not yet been determined. We therefore prospectively analyzed the effects of additional angiography and chemoembolization on HCC recurrence and survival in patients who underwent TACE and achieved complete necrosis (CN). METHODS A total of 68 patients who achieved CN after TACE, as assessed using dynamic computed tomography (CT), were randomized into two groups. Patients in the CT group (n = 34) were followed using dynamic CT every 3 months without any further intervention, whereas patients in the angiography group (n = 34) received additional angiography 1 month after achievement of CN. We compared overall survival and disease-free survival between the two groups and analyzed the benefit of additional angiography. RESULTS The cumulative recurrence rate did not differ between the angiography and CT groups (55%vs 48% at 12 months and 66%vs 67% at 24 months, P = 0.92). The overall survival rates at 12 and 24 months were 88% and 84% in the angiography group, and 88% and 70% in the CT group, respectively (P = 0.57). Of the 34 patients in the angiography group, 27 (79%) suffered from adverse reactions of additional angiography and subsequent chemoembolization, seven (20.6%) experienced serum bilirubin increases of >/=1 mg/dL over baseline, and two (5.9%) developed renal impairment. CONCLUSION Additional angiography and chemoembolization did not reduce tumor recurrence or improve patient survival in HCC patients who achieved CN, as assessed using dynamic CT, following TACE.
Collapse
Affiliation(s)
- Myoung Kuk Jang
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
31
|
Wong BW, Luk JM, Ng IO, Hu MY, Liu KD, Fan ST. Identification of liver-intestine cadherin in hepatocellular carcinoma--a potential disease marker. Biochem Biophys Res Commun 2004; 311:618-24. [PMID: 14623315 DOI: 10.1016/j.bbrc.2003.10.032] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Liver-intestine cadherin (LI-cad) is a non-classical cadherin, which is expressed during intestinal development, but absent in normal liver tissue. Our earlier investigation has detected overexpression of LI-cad in gastric adenocarcinoma and indicated its association with lymph node metastasis. Herein, we found in RT-PCR and TaqMan Q-PCR that LI-cad was identified in HCC cell lines, HuH-7, Hep-3B, and PLC/PRF/5, but not in MIHA and HepG2 non-tumorigenic cells. Immunofluorescence cytochemistry assay revealed that the LI-cad was predominantly expressed in cytoplasm of HCC cells, contrary to that of E-cad immunostain at the plasma membrane region. By testing against 18 pairs of HCC and adjacent non-tumor tissues, 13 cases (72.2%) showed over expression of LI-cad in HCC tissues, 2 cases (11.1%) were similar, and 3 cases did not yield detectable signal. None of the 6 normal liver specimens tested was positive with LI-cad. Taken together, LI-cad could be a potential disease marker for HCC.
Collapse
Affiliation(s)
- Bonnie W Wong
- Centre for the Study of Liver Disease, The University of Hong Kong, Pokfulam, Hong Kong, SAR, PR China
| | | | | | | | | | | |
Collapse
|
|
32
|
Kanematsu M, Semelka RC, Leonardou P, Mastropasqua M, Lee JKT. Hepatocellular carcinoma of diffuse type: MR imaging findings and clinical manifestations. J Magn Reson Imaging 2003; 18:189-95. [PMID: 12884331 DOI: 10.1002/jmri.10336] [Citation(s) in RCA: 92] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
PURPOSE To assess MR imaging findings and clinical manifestations of diffuse-type hepatocellular carcinoma (HCC). MATERIALS AND METHODS We retrospectively reviewed our experience with diffuse HCC from November 1994 to October 2001. MR imaging findings and clinical features were assessed. RESULTS Twenty-two consecutive patients with diffuse-type HCC (19 men and three women, age range 16-80 years [mean, 52 years]) were identified in a review of liver MR studies. This represented 13% of all patients with HCC imaged during this time period. Diffuse HCC showed a permeative, infiltrative pattern with ill-defined borders and no evidence of convex margination in all cases. At least 50% of the liver volume was involved with tumor. Diffuse-type HCC showed hypointensity in 15 patients, mixed intensity in three, and isointensity in four on T1-weighted images; heterogeneous hyperintensity in 16 patients; and homogeneous hyperintensity in six on T2-weighted MR images. Diffuse-type HCC showed patchy enhancement in 12 patients, miliary enhancement in nine, and minimal enhancement in one on postcontrast early-phase images, and showed heterogeneous wash-out in all patients on postcontrast late-phase images. Proximal portal venous tumor thrombosis was seen in all patients. Serum alpha-fetoprotein (AFP) value was elevated (>10 ng/mL) in 14 of 18 patients, and 13 showed a value greater than 500 ng/mL. The four patients who did not have elevated AFP had tumors which were indistinguishable from those in patients with elevated AFP; they also did not have a distinctive clinical history. CONCLUSION Diffuse-type HCC was typically seen as an extensive, heterogeneous permeative hepatic tumor, with portal venous tumor thrombosis on MR images in all cases. Early enhancement, observed as patchy in 12 and miliary in nine of 22 patients, was a distinctive imaging feature. Elevated serum AFP value was a common finding; however, 22% had normal values.
Collapse
Affiliation(s)
- Masayuki Kanematsu
- Department of Radiology, University of North Carolina, Chapel Hill, North Carolina 27599-7510, USA
| | | | | | | | | |
Collapse
|
|
33
|
Yao FY. Dramatic reduction of the alpha-fetoprotein level after lamivudine treatment of patients with chronic hepatitis B virus infection and cirrhosis. J Clin Gastroenterol 2003; 36:440-2. [PMID: 12702990 DOI: 10.1097/00004836-200305000-00017] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Markedly elevated alpha-fetoprotein levels in the range of >1,000 ng/mL are highly suspicious for the presence of hepatocellular carcinoma. This report describes three patients with cirrhosis and replicating hepatitis B virus infection who presented with initial serum alpha-fetoprotein levels of >1,000 ng/mL without clear evidence of hepatocellular carcinoma based on multiple abdominal imaging studies. Initiation of lamivudine treatment led to rapid and dramatic reductions in the alpha-fetoprotein level to the normal range within 12 weeks in one patient and by >1 log at 7 and 16 weeks in the other two patients. One of the three patients previously developed lamivudine resistance, and discontinuation of lamivudine led to a severe flare of hepatitis B before lamivudine treatment was restarted. During a follow-up period of 14 to 36 months, all three patients maintained stable alpha-fetoprotein levels and had no signs of hepatocellular carcinoma demonstrated by serial abdominal imaging studies. The dramatic decrease in the alpha-fetoprotein levels in these patients is unlikely to be a spontaneous event but is possibly due to suppression of viral replication and associated hepatic inflammatory activities by lamivudine. These observations may be helpful in the diagnostic evaluation and management of patients with markedly elevated alpha-fetoprotein levels and chronic hepatitis B-related cirrhosis.
Collapse
Affiliation(s)
- Francis Y Yao
- Department of Medicine, Division of Gastroenterology, University of California, San Francisco 94143, USA.
| |
Collapse
|
|
34
|
Abstract
Liver transplantation plays an important role in the treatment of patients with fulminant hepatic failure (FHF). Early determination of prognosis in cases of FHF is important to allow prompt decision-making regarding the need for liver transplantation. Mushroom poisoning is a rare cause of FHF, and as a result, prognostic criteria are not well recognized. It appears that the severity of coagulopathy and encephalopathy predicts a poor outcome, whereas the degree of bilirubin elevation may not. We present a case of FHF related to mushroom poisoning that required liver transplantation. The clinical presentation, medical management, and prognostic criteria in mushroom poisoning are discussed.
Collapse
Affiliation(s)
- James R Burton
- Department of Medicine, GI Unit-Hepatology Section Strong, Memorial Hospital, Rochester, New York, USA.
| | | | | |
Collapse
|
|
35
|
Song BC, Chung YH, Kim JA, Choi WB, Suh DD, Pyo SI, Shin JW, Lee HC, Lee YS, Suh DJ. Transforming growth factor-beta1 as a useful serologic marker of small hepatocellular carcinoma. Cancer 2002; 94:175-80. [PMID: 11815974 DOI: 10.1002/cncr.10170] [Citation(s) in RCA: 94] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Although alpha-fetoprotein (AFP) is a useful serologic marker of hepatocellular carcinoma (HCC), it has been reported insufficiently sensitive in detecting small HCCs. Plasma transforming growth factor-beta1 (TGFbeta1) has been reported to be elevated in HCC patients compared with liver cirrhosis patients. It has been reported that TGFbeta1 mRNA was overexpressed in HCC, especially in patients with small HCC and well-differentiated HCC compared with patients with liver cirrhosis. The current study investigated the usefulness of TGFbeta1 compared with AFP in the diagnosis of small HCCs. METHODS Thirty-eight patients with small HCC (< or = 3 cm), 31 patients with liver cirrhosis only, and 23 normal volunteers were studied. Using plasma TGFbeta1 and serum AFP levels measured at the time of diagnosis, the sensitivities and specificities were calculated in the diagnosis of small HCCs. RESULTS Plasma TGFbeta1 and serum AFP levels were significantly higher in patients with small HCC than in those with liver cirrhosis. In diagnosing small HCCs, the cut-off values of plasma TGFbeta1 and serum AFP were 800 pg/mL and 200 ng/mL, respectively, where the specificities were over 95%. At the cut-off level of plasma TGFbeta1 and serum AFP, the sensitivities were 68% and 24%, respectively. CONCLUSIONS The current results suggest that TGFbeta1 may be a useful serologic marker in detecting HCCs earlier because it shows higher sensitivity than, with specificity as, AFP in the diagnosis of small HCCs.
Collapse
Affiliation(s)
- Byung-Cheol Song
- Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Choi BI, Kim AY, Lee JY, Kim KW, Lee KH, Kim TK, Han JK. Hepatocellular carcinoma: contrast enhancement with Levovist. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2002; 21:77-84. [PMID: 11794406 DOI: 10.7863/jum.2002.21.1.77] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
OBJECTIVE To present the sonographic appearance of hepatocellular carcinoma imaged with the intravenous contrast agent Levovist. METHODS We reviewed our experience using Levovist (Schering AG, Berlin, Germany) for the sonographic diagnosis of hepatocellular carcinoma. RESULTS Contrast-enhanced sonography with Levovist facilitated detailed evaluation of tumor vascularity in hepatocellular carcinoma. CONCLUSIONS Contrast-enhanced sonography with Levovist enhances the role of sonography in the diagnosis of hepatocellular carcinoma. It provides detailed information about tumor vascularity and the contrast enhancement pattern.
Collapse
Affiliation(s)
- Byung Ihn Choi
- Department of Radiology and Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Korea
| | | | | | | | | | | | | |
Collapse
|
|
37
|
|
|
38
|
Aranìbar N, Singh BK, Stockton GW, Ott KH. Automated mode-of-action detection by metabolic profiling. Biochem Biophys Res Commun 2001; 286:150-5. [PMID: 11485321 DOI: 10.1006/bbrc.2001.5350] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Rapid classification and identification of the mode-of-action of bioactive compounds applied to plants can be achieved by a robust and easy-to-use metabolic-profiling method. This method uses artificial neural network analysis of one-dimensional proton NMR spectra of aqueous plant extracts to rapidly classify changes in the total metabolic profile caused by application of crop protection chemicals.
Collapse
Affiliation(s)
- N Aranìbar
- BASF Agro Research, Princeton, NJ 08543-0400, USA
| | | | | | | |
Collapse
|
|
39
|
Trevisani F, D'Intino PE, Morselli-Labate AM, Mazzella G, Accogli E, Caraceni P, Domenicali M, De Notariis S, Roda E, Bernardi M. Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status. J Hepatol 2001; 34:570-5. [PMID: 11394657 DOI: 10.1016/s0168-8278(00)00053-2] [Citation(s) in RCA: 513] [Impact Index Per Article: 21.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND It is not established whether virological status affects the efficiency of alpha-fetoprotein (AFP) as a hepatocellular carcinoma (HCC) marker among patients with chronic liver disease (CLD). METHODS We enrolled in a case-control study 170 HCC and 170 CLD patients, matched for age, sex, CLD and HBsAg/anti-HCV status. The AFP sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated. PPV and NPV were evaluated for three additional HCC prevalences (5, 10, and 20%). RESULTS The best discriminating AFP value was 16 ng/ml. A value of 20 ng/ml (above which investigations for HCC are recommended) had equivalent sensitivity (60.0 vs. 62.4%) and specificity (90.6 vs. 89.4%). PPV of 20 ng/ml was 84.6% but decreased to 25.1% at 5% tumor prevalence. NPV was 69.4% and rose to 97.7% at 5% prevalence. In the different groups of infected patients PPV ranged from 80.0 to 90.9%, falling to 17.4-34.5% at 5% prevalence. In noninfected patients PPV was 100% at any HCC prevalence. NPV ranged from 59.0 to 73.0%, reaching 96.5-98.1% at 5% prevalence. CONCLUSIONS In CLD patients, AFP monitoring misses many HCCs and inappropriately arouses suspicion of malignancy in many patients. Its usefulness is barely affected by the infection responsible for CLD. An AFP elevation could be more indicative of HCC in non-infected patients.
Collapse
Affiliation(s)
- F Trevisani
- Dipartimento di Medicina Interna, Cardioangiologia, Epatologia, University of Bologna, Italy.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
40
|
Johnson PJ. The role of serum alpha-fetoprotein estimation in the diagnosis and management of hepatocellular carcinoma. Clin Liver Dis 2001; 5:145-59. [PMID: 11218912 DOI: 10.1016/s1089-3261(05)70158-6] [Citation(s) in RCA: 259] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Forty years after its discovery, estimation of serum AFP remains a useful test for clinicians involved in management of patients with HCC or chronic liver disease. The test, when used with the conventional cut-off point of 500 ng/mL, has a sensitivity of about 50% and a specificity of more than 90% in detecting the presence of HCC in a patient with coexisting liver disease. New tests that can significantly increase the specificity at lower levels (i.e., between 10 and 500 ng/mL) are available but have, to date, been too complex to be widely applied in clinical practice. Serum AFP estimation may also be useful in monitoring response to therapy, particularly as more effective systemic regimens are becoming available. Indeed, there is preliminary evidence that changes in serum AFP may be a more accurate and sensitive way of determining the degree of response to treatment than conventional imaging procedures that rely on physical determination of tumor size. It may, perhaps, be time to add changes in serum AFP to the conventional imaging criteria for assessing response in clinical trials.
Collapse
Affiliation(s)
- P J Johnson
- Department of Clinical Oncology, Chinese University of Hong Kong Prince of Wales Hospital, Shatin, Hong Kong SAR, China
| |
Collapse
|
|
41
|
Tangkijvanich P, Anukulkarnkusol N, Suwangool P, Lertmaharit S, Hanvivatvong O, Kullavanijaya P, Poovorawan Y. Clinical characteristics and prognosis of hepatocellular carcinoma: analysis based on serum alpha-fetoprotein levels. J Clin Gastroenterol 2000; 31:302-308. [PMID: 11129271 DOI: 10.1097/00004836-200012000-00007] [Citation(s) in RCA: 229] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The purpose of this study was to determine whether a relation does exist between clinicopathologic features and the prognosis of hepatocellular carcinoma (HCC) with respect to serum alpha-fetoprotein (AFP) levels at diagnosis. We reviewed the clinical data of 309 pathologically proven HCC cases divided into three groups: group 1 with normal AFP (<20 IU/mL), group 2 with moderately elevated AFP (20-399 IU/mL) and group 3 with markedly elevated AFP (> or =400 IU/mL). Of these, there were 76 (24.6%), 78 (25.2%), and 155 patients (50.2%) in groups 1, 2, and 3, respectively. We found that HCC patients with high AFP tended to have greater tumor size, bilobar involvement, massive or diffuse types, and portal vein thrombosis. Nonetheless, we could not establish a correlation between increased AFP and Okuda's stages, degree of tumor differentiation, or extrahepatic metastasis. The median survival rates in groups 1 (6 months) and 2 (7 months) were significantly longer than that of group 3 (3 months). On multivariate logistic regression analysis, positive hepatitis B surface antigen (HBsAg) status and bilobar tumor involvement represented the independent factors for predicting high AFP values. We concluded that AFP is useful not only for diagnosis, but also as a prognostic indicator in patients with HCC . However, it cannot be considered a sensitive tumor marker, particularly during the early stages in HBsAg-negative patients.
Collapse
Affiliation(s)
- P Tangkijvanich
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | | | | | | | | | | | | |
Collapse
|
|
42
|
Abstract
Screening for hepatocellular carcinoma has become widely practised in the management of patients with end-stage liver disease. However, the theoretical basis for this practice is largely lacking. Issues such as the selection of the target population and the correct method of confirming positive screening tests have yet to be resolved. Complicating the assessment of screening strategies is the poor literature on comparing different forms of therapy. Nonrandomized, uncontrolled studies that do not account for lead-time bias make it frequently impossible to know whether an applied treatment has really improved survival. Despite these difficulties, screening is reality, and strategies have to be devised to efficiently screen patients, find small tumours and apply effective treatments. Some practical strategies are discussed.
Collapse
Affiliation(s)
- M Sherman
- Department of Medicine, University of Toronto and The Toronto Hospital, Canada
| |
Collapse
|
|
43
|
Yao FY. Elevated alpha-fetoprotein levels in hepatocellular carcinoma. Am J Gastroenterol 1999; 94:3387. [PMID: 10566766 DOI: 10.1111/j.1572-0241.1999.03387.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
|
|
44
|
Ng FH, Chow KC, Cheng CS, Kng C, Ng WF, Wong BC. High alpha-fetoprotein level in HCV-related nodular liver cell dysplasia. Am J Gastroenterol 1999; 94:2296-7. [PMID: 10445567 DOI: 10.1111/j.1572-0241.1999.01319.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The diagnosis of hepatocellular carcinoma is generally made in patients with a mass lesion in the cirrhotic liver if the alpha-fetoprotein level is >1,000 ng/L. Other causes of elevation of alpha-fetoprotein to this extreme degree include nonseminomatous germ cell tumor and hepatic metastasis. However, it is extremely rare for benign hepatic lesions to cause alpha-fetoprotein of > 1,000 ng/ml. We report a Chinese patient with spontaneous normalization of alpha-fetoprotein with an initial value > 10,000 ng/ml due to nodular dysplasia complicating hepatitis C-related liver cirrhosis. The alpha-fetoprotein was secreted from the dysplastic liver cells.
Collapse
Affiliation(s)
- F H Ng
- Department of Medicine, Ruttonjee Hospital, Wan Chai, Hong Kong, China
| | | | | | | | | | | |
Collapse
|
|
45
|
Chiaramonte M, Stroffolini T, Vian A, Stazi MA, Floreani A, Lorenzoni U, Lobello S, Farinati F, Naccarato R. Rate of incidence of hepatocellular carcinoma in patients with compensated viral cirrhosis. Cancer 1999. [DOI: 10.1002/(sici)1097-0142(19990515)85:10<2132::aid-cncr6>3.0.co;2-h] [Citation(s) in RCA: 179] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
|
|
46
|
He P, Tang ZY, Ye SL, Liu BB. Relationship between expression of α-fetoprotein messenger RNA and some clinical parameters of human hepatocellular carcinoma. World J Gastroenterol 1999; 5:111-115. [PMID: 11819405 PMCID: PMC4688518 DOI: 10.3748/wjg.v5.i2.111] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To certify the relationship between AFP-mRNA and some pathological parameters of he patocellular carcinoma (HCC).
METHOD We detected the expression of AFP in mRNA level in tissue samples from 52 patients suffering from HCC by RT-PCR method.
RESULTS The positive rate of AFP mRNA was 76.9% in the HCC tumor tissues, and 69.4% in the paratumor tissues from the HCC patients with severe cirrhosis. However, in HCC patients without cirrhosis, the positive rate reached 50% in tumor tissues, but no AFP mRNA expression was found in the related paratumor tissues.
CONCLUSION The AFP protein was specially expressed by HCC cells and mutated hepatocytes. The AFP mRNA was positively related with cirrhosis, but no significant relationship was found between AFP mRNA and tumor size, capsule status and tumor metastasis.
Collapse
|
|
47
|
Stroffolini T, Andreone P, Andriulli A, Ascione A, Craxi A, Chiaramonte M, Galante D, Manghisi OG, Mazzanti R, Medaglia C, Pilleri G, Rapaccini GL, Simonetti RG, Taliani G, Tosti ME, Villa E, Gasbarrini G. Characteristics of hepatocellular carcinoma in Italy. J Hepatol 1998; 29:944-952. [PMID: 9875641 DOI: 10.1016/s0168-8278(98)80122-0] [Citation(s) in RCA: 119] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND/AIMS This study aimed to assess the main features of hepatocellular carcinoma at the time of diagnosis in Italy, particularly in relation to the presence or absence of underlying cirrhosis, hepatitis virus marker patterns, age of the subjects and alpha-foetoprotein values. METHODS A total of 1148 patients with hepatocellular carcinoma seen at 14 Italian hospitals in the 1-year period from May 1996 to May 1997 were the subjects of this prevalence study. Both newly diagnosed cases (incident cases) and cases diagnosed before May 1996 but still attending the hospitals during the study period (prevalent cases) were included. RESULTS We found that 71.1% of cases were positive for hepatitis C virus antibodies but negative for HBsAg; in contrast, 11.5% were negative for anti-HCV but positive for HBsAg; 5.3% were positive for both markers; and 12.1% were negative for both viruses. The mean age of detection was over 60 years, with a younger mean age in HBsAg-positive compared to anti-HCV-positive patients (59.3 years vs. 65.6 years, p<0.01). The male-to-female ratio among HBsAg-positive patients was 10.4:1, in contrast to 2.8:1 among anti-HCV-positive patients (p<0.01). The majority of cases (93.1%) had underlying cirrhosis. Cirrhotic patients were more likely to be anti-HCV positive than non-cirrhotic cases (73.2% vs 43.9%; p<0.01); conversely, absence of hepatitis virus markers was more frequently observed in the non-cirrhotic than in the cirrhotic population (40.9% vs. 10.0%; p<0.01). Overall, the alpha-foetoprotein level was altered (>20 ng/ml) in 57.9% of patients; only 18% of cases presented diagnostic (>400 ng/ml) values. Anti-HCV positivity (O.R. 2.0; CI 95%=1.3-3.1) but not HBsAg positivity (O.R. 1.0; CI 95%=0.6-1.8) was shown to be an independent predictor of the likelihood of altered alpha-foetoprotein values by multivariate analysis. CONCLUSIONS These findings point to differences in the characteristics of the populations infected by hepatitis B and hepatitis C. Factors other than the hepatitis viruses are important in non-cirrhotic patients. A change in the relative prevalence of hepatitis virus markers among hepatocellular carcinoma cases was demonstrated, reflecting a significant change in the rate of HBV endemicity in the Italian population. Finally, the increased trend in the mortality rate from liver cancer in Italy from 4.8 per 100,000 in 1969 to 10.9 in 1994 may reflect the large cohort of subjects infected with HCV via the iatrogenic route during 1950s and 1960s when glass syringes were commonly used for medical treatment.
Collapse
|
|
48
|
Affiliation(s)
- J Collier
- The Toronto Hospital, Ontario, Canada
| | | |
Collapse
|
|
49
|
Paul C, Thomas M. Screening for hepatitis B carriers: a perspective from New Zealand. AUSTRALIAN AND NEW ZEALAND JOURNAL OF MEDICINE 1997; 27:698-705. [PMID: 9483239 DOI: 10.1111/j.1445-5994.1997.tb01001.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- C Paul
- Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand
| | | |
Collapse
|
|
50
|
Johnson PJ, Leung N, Cheng P, Welby C, Leung WT, Lau WY, Yu S, Ho S. 'Hepatoma-specific' alphafetoprotein may permit preclinical diagnosis of malignant change in patients with chronic liver disease. Br J Cancer 1997; 75:236-40. [PMID: 9010032 PMCID: PMC2063272 DOI: 10.1038/bjc.1997.39] [Citation(s) in RCA: 45] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
The only hope for effective treatment of hepatocellular carcinoma (HCC or 'hepatoma') lies in early diagnosis. Measurement of the serum alphafetoprotein (AFP) level is potentially a useful screening test. When grossly raised, it is almost diagnostic of HCC. However, modestly elevated levels may also arise in patients with benign chronic liver disease, and this markedly decreases the test's specificity and hence its clinical value. In 582 consecutive attendees at an outpatient clinic for people with chronic liver disease, a single blood sample was taken for analysis of 'total' AFP and the 'hepatoma-specific' AFP isoform. Using ultrasonography as the primary screening method, patients with AFP levels > or = 50 ng ml-1 were followed up throughout the study or until HCC was diagnosed on the basis of conventionally defined criteria. On entry into the study, 53 patients had an AFP concentration > = or 50 ng ml-1 and the 'hepatoma-specific' AFP isoform was detected in 26 of these. During an 18-month follow-up period, a diagnosis of HCC was established by conventional methods in 19 (17 'definite' and two 'probable') of these 26 patients. In only two cases was there ultrasound evidence of tumour development at the time AFP was first found to be elevated; in the remainder a diagnosis of HCC, based on ultrasound screening, was established at a median time of 3.6 months (range 1-18 months) after entry into the study. Among those 27 without the 'hepatoma-specific' isoform, one developed a 'definite' HCC and two developed 'probable' tumours. With the application of 'hepatoma-specific' AFP, the positive predictive value of the test was 73.1%, compared with only 41.5% using the conventional 'total' AFP test. Application of this test for the 'hepatoma-specific' AFP markedly increases the positive predictive value of AFP and, in some cases, permits the presence of tumour to be inferred before it could be detected by routine ultrasound examination.
Collapse
Affiliation(s)
- P J Johnson
- Hepatoma Study Group, Sir YK Pao Cancer Centre, Shatin, NT, Hong Kong
| | | | | | | | | | | | | | | |
Collapse
|