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Comprehensive evaluation of microRNA as a biomarker for the diagnosis of hepatocellular carcinoma

World Journal of Gastroenterology 2022年第29期28卷 3917-3933页

作者： Juliane Malik Martin Klammer Vinzent Rolny Henry Lik-Yuen Chan Teerha Piratvisuth Tawesak Tanwandee Satawat Thongsawat Wattana Sukeepaisarnjaroen Juan Ignacio Esteban Marta Bes Bruno Kohler Magdalena Swiatek-de Lange Diagnostics GmbH Penzberg 82377Germany Faculty of Medicine The Chinese University of Hong KongHong Kong 999077China NKC Institute of Gastroenterology and Hepatology Songklanagarind HospitalHat Yai 90112Thailand Division of Gastroenterology Faculty of MedicineSiriraj HospitalMahidol UniversityBangkok 10700Thailand Department of Internal Medicine Maharaj Nakorn Chiang Mai HospitalChiang Mai UniversityChiang Mai 50200Thailand Faculty of Medicine Srinagarind HospitalKhon Kaen UniversityKhon Kaen 40000Thailand Liver Unit Vall d’Hebron University HospitalBarcelona 08035Spain Transfusion Safety Laboratory Banc de Sang i TeixitsBarcelona 08005Spain Department of Medical Oncology National Center for Tumor DiseasesUniversity Hospital HeidelbergHeidelberg 69120Germany Liver Cancer Center Heidelberg University Hospital HeidelbergHeidelberg 69120Germany

BACKGROUND Hepatocellular carcinoma(HCC) is the most common type of primary liver cancer. Current guidelines for HCC management recommend surveillance of high-risk patients every 6 mo using ultrasonography. Serum biomarkers, like alpha-fetoprotein(AFP), protein induced by vitamin K absence/antagonist-Ⅱ(PIVKA-Ⅱ) and lectin-reactive AFP, show suboptimal performance for detection of HCC, which is crucial for successful resection or treatment. Thus, there is a significant need for new biomarkers to aid early diagnosis of HCC. Studies have shown that the expression level of human microRNAs(miRNAs), a small, non-coding RNA species released into the blood, can serve as an early marker for various diseases, including *** To evaluate the diagnostic role of miRNAs in HCC as single markers, signatures or in combination with known protein *** Our prospective, multicenter, case-control study recruited 660 participants(354 controls with chronic liver disease and 306 participants with HCC) and employed a strategy of initial screening by two independent methods, real-time quantitative PCR(n = 60) and next-generation sequencing(n = 100), to assess a large number of miRNAs. The results from the next-generation sequencing and real-time quantitative PCR screening approaches were then combined to select 26 miRNAs(including two putative novel miRNAs). Those miRNAs were analyzed for their diagnostic potential as single markers or in combination with other miRNAs or established protein biomarkers AFP and PIVKA-Ⅱ via real-time quantitative PCR in training(n = 200) and validation cohorts(n = 300).RESULTS We identified 26 miRNAs that differentiated chronic liver disease controls from(early) HCC via two independent discovery approaches. Three miRNAs, miR-21-5p(miR-21), miR-320a and miR-186-5p, were selected by both methods. In the training cohort, only miR-21, miR-320d and miR-423could significantly distinguish(Q < 0.05) between the HCC and chronic liver disease control grou

关键词： Carcinoma Hepatocellular MicroRNAs Biomarkers alpha-fetoprotein Protein induced by vitamin K absence-Ⅱ Diagnosis

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Development and in vitro study of a bi-specific magnetic resonance imaging molecular probe for hepatocellular carcinoma

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World Journal of Gastroenterology 2019年第24期25卷 3030-3043页

作者： Xiao-Hong Ma Shuang Wang Si-Yun Liu Kun Chen Zhi-Yuan Wu Deng-Feng Li Yong-Tao Mi Long-Bin Hu Zhong-Wei Chen Xin-Ming Zhao Department of Diagnostic Radiology National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China GE Healthcare (China) Beijing 100176China State Key Laboratory of Molecular Oncology National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijing 100021China

BACKGROUND Hepatocellular carcinoma(HCC)ranks second in terms of cancer mortality *** magnetic resonance imaging(MRI)targeting HCC biomarkers such as alpha-fetoprotein(AFP)or glypican-3(GPC3)offers new strategies to enhance specificity and help early diagnosis of ***,the existing iron oxide nanoparticle-based MR molecular probes singly target AFP or GPC3,which may hinder their efficiency to detect heterogeneous micro malignant HCC tumors<1 cm(MHCC).We hypothesized that the strategy of double antibody-conjugated iron oxide nanoparticles which simultaneously target AFP and GPC3 antigens may potentially be used to overcome the tumor heterogeneity and enhance the detection rate for MRI-based MHCC *** To synthesize an AFP/GPC3 double antibody-labeled iron oxide MRI molecular probe and to assess its impact on MRI specificity and sensitivity at the cellular *** A double antigen-targeted MRI probe for MHCC anti-AFP-USPIO-anti-GPC3(UAG)was developed by simultaneously conjugating AFP andGPC3 antibodies to a 5 nm ultra-small superparamagnetic iron oxide nanoparticle(USPIO).At the same time,the singly labeled probes of anti-AFP-USPIO(UA)and anti-GPC3-USPIO(UG)and non-targeted USPIO(U)were also prepared for *** physical characterization including morphology(transmission electron microscopy),hydrodynamic size,and zeta potential(dynamic light scattering)was conducted for each of the *** antigen targeting and MRI ability for these four kinds of USPIO probes were studied in the GPC3-expressing murine hepatoma cell line Hepa1-6/***,AFP and GPC3 antigen expression in Hepa1-6/GPC3 cells was confirmed by flow cytometry and ***,the cellular uptake of USPIO probes was investigated by Prussian blue staining assay and in vitro MRI(T2-weighted and T2-map)with a 3.0 Tesla clinical MR *** Our data showed that the double antibody-conjugated probe UAG had the best specificity in targeting Hepa1-

关键词： Hepatocellular carcinoma Molecular imaging Magnetic resonance imaging Ultra-small superparamagnetic iron nanoparticles alpha-fetoprotein Glypican-3

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Adult mouse model of early hepatocellular carcinoma promoted by alcoholic liver disease

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World Journal of Gastroenterology 2016年第16期22卷 4091-4108页

作者： Aditya Ambade Abhishek Satishchandran Benedek Gyongyosi Patrick Lowe Gyongyi Szabo Department of Medicine University of Massachusetts Medical School

AIM: To establish a mouse model of alcohol-driven hepatocellular carcinoma (HCC) that develops in livers with alcoholic liver disease (ALD).METHODS: Adult C57BL/6 male mice received multiple doses of chemical carcinogen diethyl nitrosamine (DEN) followed by 7 wk of 4% Lieber-DeCarli diet. Serum alanine aminotransferase (ALT), alpha fetoprotein (AFP) and liver Cyp2e1 were assessed. Expression of F4/80, CD68 for macrophages and Ly6G, MPO, E-selectin for neutrophils was measured. Macrophage polarization was determined by IL-1β/iNOS (M1) and Arg-1/IL-10/CD163/CD206 (M2) expression. Liver steatosis and fibrosis were measured by oil-red-O and Sirius red staining respectively. HCC development was monitored by magnetic resonance imaging, confirmed by histology. Cellular proliferation was assessed by proliferating cell nuclear antigen (PCNA).RESULTS: Alcohol-DEN mice showed higher ALTs than pair fed-DEN mice throughout the alcohol feeding without weight gain. Alcohol feeding resulted in increased ALT, liver steatosis and inflammation compared to pair-fed controls. Alcohol-DEN mice had reduced steatosis and increased fibrosis indicating advanced liver disease. Molecular characterization showed highest levels of both neutrophil and macrophage markers in alcohol-DEN livers. Importantly, M2 macrophages were predominantly higher in alcohol-DEN livers. Magnetic resonance imaging revealed increased numbers of intrahepatic cysts and liver histology confirmed the presence of early HCC in alcohol-DEN mice compared to all other groups. This correlated with increased serum alpha-fetoprotein, a marker of HCC, in alcohol-DEN mice. PCNA immunostaining revealed significantly increased hepatocyte proliferation in livers from alcohol-DEN compared to pair fed-DEN or alcohol-fed ***: We describe a new 12-wk HCC model in adult mice that develops in livers with alcoholic hepatitis and defines ALD as co-factor in HCC.

关键词： alpha-fetoprotein Macrophage polarization Steatohepatitis Proliferating cell nuclear antigen Liver tumor

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Immunotherapy for hepatocellular carcinoma:Current status and future perspectives

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World Journal of Gastroenterology 2023年第6期29卷 1054-1075页

作者： Deepa S Mandlik Satish K Mandlik Heena B Choudhary Department of Pharmacology BVDUPoona College of PharmacyPune 411038MaharashtraIndia Department of Pharmaceutics BVDUPoona College of PharmacyPune 411038MaharashtraIndia

Hepatocellular carcinoma(HCC)is one of the world’s deadliest and fastestgrowing tumors,with a poor *** develops in the context of chronic liver *** resection,surgery(liver transplantation),trans-arterial chemoembolization,radioembolization,radiofrequency ablation and chemotherapy are common treatment options for HCC,however,they will only assist a limited percentage of *** treatments for advanced HCC are ineffective and aggravate the underlying liver *** promising preclinical and early-phase clinical trials for some drugs,existing systemic therapeutic methods for advanced tumor stages remain limited,underlining an unmet clinical *** current years,cancer immunotherapy has made significant progress,opening up new treatment options for ***,on the other hand,has a variety of causes and can affects the body’s immune system via a variety of *** the speedy advancement of synthetic biology and genetic engineering,a range of innovative immunotherapies,such as immune checkpoint inhibitors[anti-programmed cell death-1(PD-1),anti-cytotoxic T lymphocyte antigen-4,and anti-PD ligand 1 cell death antibodies],therapeutic cancer vaccines,engineered cytokines,and adoptive cell therapy have all been used for the treatment of advanced *** this review,we summarize the present clinical and preclinical landscape of immunotherapies in HCC,critically discuss recent clinical trial outcomes,and address future perspectives in the field of liver cancer.

关键词： Hepatocellular carcinoma Immunotherapy Immune checkpoint inhibitors alpha-fetoprotein Cancer vaccine Combination therapies

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AFP level and histologic differentiation predict the survival of patients with liver transplantation for hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2012年第3期11卷 256-261页

作者： Onur Yaprak Murat Akyildiz Murat Dayangac Baha Tolga Demirbas Necdet Guler Gulen Bulbul Dogusoy Yildiray Yuzer Yaman Tokat Organ Transplantation Center Sisli Florence Nightingale Hospital

BACKGROUND: In liver transplantation or resection for hepatocellular carcinoma (HCC), patient selection depends on morphological features. In patients with HCC, we performed a clinicopathological analysis of risk factors that affected survival after liver transplantation. METHODS: In 389 liver transplantations performed from 2004 to 2010, 102 were for HCC patients. Data were collected retrospectively from the Organ Transplantation Center Database. Variables were as follows: age, gender, preoperative alpha-fetoprotein (AFP) levels, Child-Pugh and MELD scores, prognostic staging criteria (Milan and UCSF), etiology, number of tumors, the largest tumor size, total tumor size, multifocality, intrahepatic portal vein tumor thrombosis, bilobarity, and histological differentiation. RESULTS: One hundred and two patients were evaluated. The 5-year overall survival rate was 56.5%. According to the UCSF criteria, 63% of the patients were within and 37% were beyond UCSF (P=0.03). Ten patients were excluded (one with fibrolamellary HCC and 9 because of early postoperative death without HCC recurrence), and 92 patients were assessed. The mean age of the patients was 56.5±6.9 years. Sixty-two patients underwent living donor liver transplantations. The mean follow-up time was 29.4±22.6 months. Fifteen patients (16.3%) died in the follow-up period due to HCC recurrence. Univariate analysis showed that AFP level, intrahepatic portal vein tumor thrombosis, histologic differentiation and UCSF criteria were significant factors related to survival and tumor recurrence. The 5-year estimated overall survival rate was 62.2% in allpatients. According to the UCSF criteria, and the 5-year overall survival rate was 66.7% within and 52.7% beyond the criteria (P=0.04). Multivariate analysis showed that AFP level and poor differentiation were independent factors. CONCLUSIONS: For proper patient selection in liver trans- plantation for HCC, prognostic criteria related to tumor biology (especially AF

关键词： liver transplantation hepatocellular carcinoma alpha-fetoprotein

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Low utility of plasma Nociceptin/orphanin FQ in the diagnosis of hepatocellular carcinoma

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World Journal of Gastroenterology 2006年第29期12卷 4716-4720页

作者： Aldo Spadaro Antonino Ajello Carmelo Luigiano Carmela Morace Maria Letizia Resta Grazia Berlinghieri Salvatore Campo Claudio Scisca Angela Alibrandi Graziella D'arrigo Nunziata Alessi Oscar Ferraù Maria Antonietta Freni Dipartimento Clinico Sperimentale di Medicina e Farmacologia Clinica Medica Pad.CAOUVia Consolare Valeria No.1Messina 98125Italy

AIM： The utility of serum alpha-fetoprotein （α-FP） in the detection of hepatocellular carcinoma （HCC） is questionable. Very high circulating levels of nociceptin/ orphanin FQ （N/OFQ）, a ligand for a novel opioid receptor, have recently been reported in HCC. The aim of this study was to assess the role of plasma N/OFQ in the diagnosis of HCC arising in patients with liver cirrhosis. METHODS： Plasma N/OFQ levels were measured by ELISA in 58 patients （28 HCC and 30 liver cirrhosis） and in 25 healthy controls. The values were correlated with clinical and laboratory features including α-FP. Spearman index, biserial correlation coefficient, non parametric combination （NPC） test and discriminant stepwise analysis were used for statistical evaluation of data.RESULTS： The upper normal limit of nociceptin was 122 pg/mL. Plasma levels above this cut-off were found in 21.4% of patients with HCC, in 23.3% of those with cirrhosis and in 8% of healthy subjects. α-FP serum levels〉200 ng/mL were found in 46.4% of the patients with HCC and in none of those with cirrhosis. No correlation was found between N/OFQ levels and any of the clinical and laboratory features, including α-FP. By NPC test, HCC and cirrhotic patients were different with regard to α-FP （P = 0.000） but not in terms of nociceptin （P = 0.595）. By point biserial correlation, HCC presence was positively correlated with α-FP （rpb = 0.52, P = 0.000） but not with N/OFQ （rpb = 0.16, P = 0.157）. In a discriminant analysis, α-FP was significant in the Wilks test （Y = -0.709 ＋ 0.03 α-FP） and properly classified 81% of all patients and 61% of HCC. N/OFQ had lower sensitivity, specificity and predictive values than α-FP. CONCLUSION： Nociceptin is increased in patients with chronic liver disease, independently of the presence of HCC, although the underlying mechanism has yet to be clarified. We conclude it is not a useful marker for HCC.

关键词： Hepatocellular carcinoma Nociceptin/orphanin FQ Liver cirrhosis alpha-fetoprotein

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High expression of protein phosphatase 2 regulatory subunit B''alpha predicts poor outcome in hepatocellular carcinoma patients after liver transplantation

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World Journal of Gastrointestinal Oncology 2021年第7期13卷 716-731页

作者： Jia-Jia He Lei Shang Qun-Wei Yu Ning Jiao Shuang Qiu Wei-Xiong Zhu Dong-Feng Wu Yun-Er Tian Qing Zhang Clinical College of General Hospital of Chinese People's Armed Police Force Anhui Medical UniversityHefei 230032AnhuiChina Department of Organ Transplantation The Third Medical Center of Chinese PLA General HospitalBeijing 100039China Department of Health Statistics Fourth Military Medical UniversityXi'an 710032Shanxi ProvinceChina Department of Ophthalmology The Third Medical Center of Chinese PLA General HospitalBeijing 100039China

BACKGROUND Protein phosphatase 2 regulatory subunit B''alpha(PPP2R3A)gene has been reported in other tumors,but the influence of PPP2R3A gene expression on the occurrence,development,and prognosis of hepatocellular carcinoma(HCC)remains *** To investigate whether the PPP2R3A gene could be used to predict tumor recurrence and survival of HCC patients after liver transplantation(LT).METHODS Diseased liver tissues of HCC patients after LT were collected as well as their clinical data and follow-up *** immunohistochemical method was used to detect the expression of PPP2R3A protein in the tissues of 108 patients with primary liver ***χ2 test was used to analyze the relationship between PPP2R3A protein expression levels and the clinicopathological features of *** Kaplan-Meier method was used to analyze overall postoperative *** COX proportional hazard model was used to analyze adverse prognostic *** Immunohistochemistry showed that the PPP2R3A protein was mainly expressed in the cytoplasm of HCC *** to corresponding peritumoral tissues,expression was higher in HCC tissues(P≤0.001).Correlation analysis showed that high PPP2R3A expression was correlated with preoperative serum alphafetoprotein(AFP)levels(P=0.003),tumor-node-metastasis-t stage(P≤0.001),and envelope invasion(P=0.001).Univariate analysis showed that overall survival(P≤0.001)and recurrence-free survival(P=0.025)of patients with high PPP2R3A expression(≥4 points)were poor compared to those with low expression(<4 points).The overall survival rates or recurrence-free survival rates at 1,2,and 3 years with high PPP2R3A expression were 73%,38%,and 23%or 31%,23%,and 23%,*** analysis showed that high PPP2R3A expression(hazard ratio=2.900,95%confidence interval:1.411–5.960,P=0.004)was an independent survival risk factor of HCC patients after LT,and it was also an independent predictor of postoperative tumor *** study als

关键词： Protein phosphatase 2 regulatory subunit B''α Hepatocellular carcinoma Liver transplantation Prognosis alpha-fetoprotein

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Bi-specific T1 positive-contrast-enhanced magnetic resonance imaging molecular probe for hepatocellular carcinoma in an orthotopic mouse model

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World Journal of Gastrointestinal Oncology 2022年第4期14卷 858-871页

作者： Xiao-Hong Ma Kun Chen Shuang Wang Si-Yun Liu Deng-Feng Li Yong-Tao Mi Zhi-Yuan Wu Chun-Feng Qu Xin-Ming Zhao Diagnostic Radiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Molecular Oncology National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100021China GE Healthcare(China) Beijing 100176China

BACKGROUND Hepatocellular carcinoma(HCC)is the second leading cause of cancer-related ***-targeted magnetic resonance imaging(MRI)is an effective noninvasive diagnostic method that involves targeting clinically-related HCC biomarkers,such as alpha-fetoprotein(AFP)or glypican-3(GPC3),with iron oxide ***,in vivo studies of HCC-targeted MRI utilize single-target iron oxide nanoprobes as negative(T2)contrast agents,which might weaken their future clinical applications due to tumor heterogeneity and negative MRI ***-small superparamagnetic iron oxide(USPIO)nanoparticles(approximately 5 nm)are potential optimal positive(T1)contrast *** previously verified the efficiency of AFP/GPC3-double-antibody-labeled iron oxide MR molecular probe in *** To validate the effectiveness of a bi-specific probe in vivo for enhancing T1-weighted positive contrast to diagnose the early-stage *** The single-and double-antibody-conjugated 5-nm USPIO probes,including antiAFP-USPIO(UA),anti-GPC3-USPIO(UG),and anti-AFP-USPIO-anti-GPC3(UAG),were synthesized.T1-and T2-weighted MRI were performed on day 10 after establishment of the orthotopic HCC mouse *** intravenous injection of U,UA,UG,and UAG probes,T1-and T2-weighted images were obtained at 12,12,and 32 h *** the end of scanning,mice were euthanized,and a histologic analysis was performed on tumor *** T1-and T2-weighted MRI showed that absolute tumor-to-background ratios in UAG-treated HCC mice peaked at 24 h post-injection,with the T1-and T2-weighted signals increasing by 46.7%and decreasing by 11.1%,respectively,relative to pre-injection ***,T1-weighted contrast in the UAG-treated group at 24 h post-injection was enhanced 1.52-,2.64-,and 4.38-fold compared to those observed for single-targeted anti-GPC3-USPIO,anti-AFP-USPIO,and nontargeted USPIO probes,*** of U-,UA-,UG-,and UAG-treated tumor sections revealed t

关键词： Hepatocellular carcinoma Molecular imaging Magnetic resonance imaging Positive contrast agent alpha-fetoprotein Glypican-3

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Model combining pre-transplant tumor biomarkers and tumor size shows more utility in predicting hepatocellular carcinoma recurrence and survival than the BALAD models

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World Journal of Gastroenterology 2018年第12期24卷 1321-1331页

作者： Nicha Wongjarupong Gabriela M Negron-Ocasio Roongruedee Chaiteerakij Benyam D Addissie Essa A Mohamed Kristin C Mara William S Harmsen J Paul Theobald Brian E Peters Joseph G Balsanek Melissa M Ward Nasra H Giama Sudhakar K Venkatesh Denise M Harnois Michael R Charlton Hiroyuki Yamada Alicia Algeciras-Schimnich Melissa R Snyder Terry M Therneau Lewis R Roberts Division of Gastroenterology and Hepatology Mayo ClinicRochesterMN 55905United States University of Puerto Rico Medical Sciences Campus San Juan 00921Puerto Rico Department of Medicine Faculty of MedicineChulalongkorn University and King Chulalongkorn Memorial HospitalThai Red Cross SocietyBangkok 10400Thailand Division of Biomedical Statistics and Informatics Mayo ClinicRochesterMN 55905United States Division of Laboratory Medicine Department of Laboratory Medicine and PathologyMayo Clinic College of MedicineRochesterMN 55905United States Department of Radiology Mayo Clinic College of MedicineRochesterMN 55905United States Department of Transplantation Mayo Clinic FloridaJacksonvilleFL 32224United States Wako Life Sciences IncorporatedMountain ViewCA 94043United States

AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver *** BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein(AFP), Lens culinaris agglutinin-reactive AFP(AFP-L3), and des-gammacarboxyprothrombin(DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios(HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42(1.18-5.00), 1.86(0.98-3.52), and 2.83(1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48(1.15-1.91) and 1.59(1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45(1.06-1.98) and 1.38(1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65,0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant(S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter(S-LAD).

关键词： alpha-fetoprotein AFP-L3 des-gammacarboxyprothrombin BALAD BALAD-2 Hepatocellular carcinoma Liver transplant Recurrence Outcome

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Hepatoid adenocarcinoma of the colon in a patient with inflammatory bowel disease

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World Journal of Gastroenterology 2014年第35期20卷 12657-12661页

作者： Yuanyuan Chen David F Schaeffer Eric M Yoshida Division of Gastroenterology University of British Columbia Department of Pathology and Laboratory Medicine University of British Columbia

A case is presented of a 36-year-old male with primary sclerosing cholangitis-associated inflammatory bowel disease(PSC-IBD) and two synchronous stage 1 adenocarcinomata of the colon,who was initially treated with a subtotal colectomy with *** year later,the patient presented with extensive intra-abdominal lymphadenopathy and peritoneal carcinomatosis,as well as a markedly elevated serum level of alpha-fetoprotein(AFP).Fine needle aspiration biopsy of a porta hepatis lymph node revealed a metastatic hepatoid *** review of the previous colectomy specimen showed that one of the previously identified adenocarcinomata had features suggestive of a hepatoid colonic *** patient was subsequently treated with a cytotoxic regimen of FOLFOX(oxaliplatin,leucovorin,5-fluorouracil) and bevacizumab,with stable results being achieved after six *** case presents the first known report of PSC-IBD associated with synchronous typical and hepatoid adenocarcinomata of the colon and highlights the importance of considering hepatoid adenocarcinoma as a differential diagnosis in patients with an increasing serum AFP level.

关键词： Hepatoid adenocarcinoma Inflammatory bowel disease Colon cancer alpha-fetoprotein Ulcerative colitis Primary sclerosing cholangitis Recurrence Metastasis

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