Evaluation of Eight Different Clinical Staging Systems Associated with Overall Survival of Chinese Patients with Hepatocellular Carcinoma

Background： Hepatocellular carcinoma （HCC） is a common cancer in China, an area of high hepatitis B virus （HBV） infection. Although several staging systems are available, there is no consensus on the best classification to use because multiple factors, such as etiology, clinical treatment and populations could affect the survival of HCC patients. Methods： This study analyzed 743 HBV-related Chinese HCC patients who received surgery first and evaluated the predictive values of eight different commonly used staging systems in the clinic. Results： The overall 1-, 3-, 5-year survival rates and a median survival were 91.5%, 70.3%, 55.3% and 72 months respectively. Barcelona Clinic Liver Cancer （BCLC） staging systems had the best stratification ability and showed the lowest Akaike information criterion （AIC） values （2896.577）, followed by tumor-node-metastasis Th （TNM 7^th） （AIC = 2899.980）, TNM 6th （AIC = 2902.17）, Japan integrated staging score （A1C = 2918.085）, Tokyo （AIC = 2938.822）, Cancer of the Liver Italian Program score （AIC = 2941.950）, Chinese University Prognostic Index grade （AIC = 2962.027）, and Okuda （AIC = 2979.389）. Conclusions： BCLC staging system is a better staging model for HBV infection patients with HCC in Chinese population among the eight currently used staging systems. These identifications afford a large group of Chinese HCC patients with HBV infection and could be helpful to design a new staging system for a certain population.

The clinical application of endobronchial ultrasound-guided transbronchial needle aspiration for staging of lung cancer

Objective To determine the value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for staging of lung cancer. Methods The study was retrospective,a total of 52 patients underwent EBUSTBNA for known or suspected lung cancer. All patients were detected enlarged mediastinal lymph nodes on CT scan (≥ 1. 0 cm) . Results Of the 52 patients,41 patients were found with N2 or N3 disease

Histologic Classification of Thymoma and Its Relationship with Myasthenia Gravis and Clinical Stages of the Tumor

Objective： To investigate the relationship among the latest WHO classification of thymoma, myasthenia gravis （MG） and clinical stages. Methods： To review the pathological sections of 74 patients with thymoma from 1980-2004 using WHO classification （1999）, the statistical software was used to analyze the relationship among the WHO classification, MG and clinical stages. Results： （1） Two cases of type A, 23 cases of type AB, 4 cases of type B1, 27 cases of type B2, 16 cases of type B3 and 2 cases of type C were classified. Type B2 more likely accompanied MG （P〈0.05）, while none with MG occurred for type C. （2） One patient was in stage Ⅰ, 30 were in stage Ⅱ, 38 were in stage Ⅲ, and 5 were in stage Ⅳ. The latest histologic classification was significantly correlated with Masaoka stages （P〈0.01）. Conclusion： The latest WHO classification was correlated with occurrence of MG and finely reflected clinical stage. It can also evaluate the prognosis of patients.

DIFFERENTIATION OF NASAL FOSSA INVOLVEMENT AND ITS CLINICAL SIGNIFICANCE IN NASOPHARYNGEAL CARCINOMA

Objective: To evaluate the prognostic influence on local control and survival in vary patterns of nasal fossa involvement in nasopharyngeal carcinoma (NPC) after radiation therapy. Methods: Between November 1989 and July 1991, 218 patients with histologically diagnosed local-regional NPC were treated with radiotherapy. Based upon the fiberscope finding, we separated nasal fossa involvement into two types: exophytic protruding (EP), which indicated exophytic bulky tumor arising from the nasopharynx and protruding into the nasal fossa, and mucosal infiltration (MI), which indicated that the nasal cavity mucosa was clinically infiltrated by tumor. Of the 218 patients, 87 had nasal involvement. Sixty of them had a pattern of MI and another 27 had an EP component. Results: The likelihood of residual disease after irradiation, the local relapse rate, 5-year free from progression rate (FFP) and death rate associated with nasopharynx relapse (DRANP) of MI and EP were 36.7% vs 3.7%, 30.0% vs 7.4%, 26.7% vs 51.8% and 25.0% vs 3.7% with P<0.004, P<0.005, P<0.02 and P<0.03, respectively. Multivariate analysis in this selected group demonstrated that infiltration of nasal fossa mucosa was an independent prognostic factor on primary control and FFP. Conclusion: Differentiation of nasal fossa involvement according to MI or EP is of value in predicting the outcome of treatment. A specific biological difference between the MI and EP group might contribute to the statistical differences in the treatment endpoints we have observed.

Relationship between the Clinical Features and the Viral Antigen in the Extremity Blood of the Patients with Hemorrhagic Fever with Renal Syndrome

Summary: The direct immunogold silver staining (D IGSS) method was used to detect the viral antigen in the extremity blood of 67 cases of hemorrhagic fever with renal syndrome. The positive rate of viral antigen was the highest during the fever, hypotension and oligouria phrase; and the rate dropped gradually during the polyuria and convalescent phase. It is suggested that clinical staging was positively related with the percentage of the viral antigen positive cells (P<0.001). It is concluded that the positive rate was related to the extent of the injuries by direct viral attack and immune reaction. The D IGSS was proved to be fast, simple, economical, with high sensitivity and specificity.

Clinical signification of high-mobility group box 1protein(HMGB1) expression in infiltrating ductalcarcinoma breast tissue

Objective: Exploring the clinical signification of high-mobility group box 1 protein(HMGB1) expression in infiltrating ductal carcinoma(IDC) breast tissue. Methods: The expression of HMGB1 protein in IDC breast tissue was detected by immunohistochemistry, and the relations among size of tumour, lymph node metastasis, clinical staging, estrogen receptor(ER), progesterone receptor(PR) and human epidermal growth factor receptor 2(HER-2) were also analyzed. Results: Fortysix cases out of 60 cases of IDC breast tissue showed positive or strong positive HMGB1 expression(76.67%), statistical significance was observed between HMGB1 expression with clinical staging(P < 0.01), lymph node metastasis(P < 0.01), breast cancer ER(P < 0.05) and HER-2(P < 0.05), however same conclusion can not be drawn between HMGB1 with either size of tumour or PR expression(P > 0.05) in IDC breast tissue. Spearman analysis showed negative correlation between HMGB1 expression and ER, and positive correlation between HMGB1 expression and clinical staging, lymph node metastasis together with HER-2. Conclusion: It's promising that HMGB1 expression in IDC tissue can be one of biological indicators of poor prognosis.

Peripheral T-lymphocyte subpopulations in different clinical stages of chronic HBV infection correlate with HBV load

AIM： To characterize the peripheral T-cell subpopulation profiles and their correlation with hepatitis B virus （HBV） replication in different dinical stages of chronic HBV infection. METHODS： A total of 422 patients with chronic HBV infection were enrolled in this study. The patients were divided into three stages： immune-tolerant stage, immune active stage, and immune-inactive carrier stage. Composition of peripheral T-cell subpopulations was determined by flow cytometry. HBV markers were detected by enzyme-linked immunosorbent assay. Serum HBV DNA load was assessed by quantitative real-time poiymerase chain reaction.RESULTS： CD8^＋ T-cells were significantly higher in patients at the immune-tolerant stage than in patients at the immune-active and -inactive carrier stages （36.87 ± 7.58 vs 34.37 ± 9.07, 36.87 ± 7.58 vs 28.09 ± 5.64, P 〈 0.001）. The peripheral blood in patients at the immune-tolerant and immune active stages contained more CD8^＋ T-cells than CD4^＋ T-cells （36.87 ± 7.58 vs 30.23 ± 6.35, 34.37 ± 9.07 vs 30.92 ± 7.40, P 〈 0.01）, whereas the peripheral blood in patients at the immune- inactive carrier stage and in normal controls contained less CD8^＋ T-cells than CD4^＋ T-cells （28.09 ± 5.64 vs 36.85 ±6.06, 24.02 ± 4.35 vs 38.94 ± 3.39, P 〈 0.01）. ANOVA linear trend test showed that CD8^＋ T-cells were significantly increased in patients with a high viral load （39.41 ± 7.36, 33.83 ± 7.50, 31.81 ± 5.95 and 26.89 ± 5.71, P 〈 0.001）, while CD4^＋ T-cells were significantly increased in patients with a low HBV DNA load （37.45 ± 6.24, 33.33 ± 5.61, 31.58 ± 6.99 and 27.56 ± 5.49, P 〈 0.001）. Nultiple regression analysis displayed that log copies of HBV DNA still maintained its highly significant coefficients for T-cell subpopulations, and was the strongest predictors for variations in CD3^＋, CD4^＋ and CD8^＋ cells and CD4^＋/CD8^＋ ratio after adjustment for age at HBV-infection, maternal HBV-infection status, presence of hepatitis B e antigen and HBV mutation.CONCLUSION： Differences in peripheral T-cell subpopulation profiles can be found in different clinical stages of chronic HBV infection. T-cell impairment is significantly associated with HBV load.

Clinical stages of recurrent hepatocellular carcinoma: A retrospective cohort study

BACKGROUND Hepatocellular carcinoma(HCC)is the second leading cause of cancer-related death worldwide,and has relatively high recurrence rates.Few studies have been published on the clinical stages of recurrent HCC.AIM To assess the applicability of the Barcelona Clinic Liver Cancer(BCLC)staging for recurrent HCC and the need to establish clinical stage criteria for recurrent HCC.METHODS The clinicopathological data of 81 patients with recurrent HCC who were admitted to the Hospital of Guangxi Zhuang Autonomous Region from January 2013 to December 2017 were collected.The patients were divided into three groups according to the BCLC staging system as follows:(1)Group A with BCLC stage A,51 patients;(2)Group B with BCLC stage B,14 patients;and(3)Group C with BCLC stage C,16 patients.The median time to tumor recurrence and the median overall survival were compared.RESULTS The median time to tumor recurrence in groups A,B,and C was 16±1.5 mo,10±2.8 mo,and 6±0.5 mo,respectively,with a statistically significant difference among them(χ^(2)=70.144,P<0.05);no statistically significant difference was noted between group A and group B(χ^(2)=2.659,P>0.05),although there were statistically significant differences between group A and group C and between group B and group C(χ^(2)=62.110,and 19.972,P<0.05).The median overall survival in groups A,B,and C were 42±5.1 mo,22±3.1 mo,and 13±1.8 mo,respectively,with a statistically significant difference among them(χ2=38.949,P<0.05);there were statistically significant differences between group A and group B,group A and group C,and group B and group C(χ2=9.577,37.172,and 7.183,respectively;P<0.05).CONCLUSION There are different prognoses in recurrent HCC patients according to the BCLC staging.Therefore,BCLC staging is applicable to recurrent HCC and it is essential to formulate clinical stage criteria for recurrent HCC.

Clinical outcomes in patients with stage non-seminomatous germ cell cancer

This study assesses the long-term outcomes in Han Chinese patients with clinical stage I non-seminomatous germ cell testicular cancer （CSI NSGCT） treated with surveillance, retroperitoneal lymph node dissection （RPLND） and adjuvant chemotherapy. We retrospectively evaluated 89 patients with a mean age of 26.5 years. After orchiectomy, 37 patients were treated with surveillance, 34 underwent RPLND and 18 were managed with chemotherapy. The overall survival rate, the recurrence-free survival rate and the risk factors were evaluated. The median follow-up length was 92 months （range： 6-149 months）. Thirteen of the 89 patients （14.6%） had relapses, and one died by the evaluation date. The overall survival rate was 98.9%. The cumulative 4-year recurrence-free rates were 80.2%, 92.0% and 100% for the surveillance, RPLND and chemotherapy groups, respectively. The disease-free period tended to be briefer in patients with a history of cryptorchidism and those with stage Is. Therefore, surveillance, RPLND and adjuvant chemotherapy might be reliable strategies in compliant patients with CSI NSGCT. Surveillance should be recommended for patients with the lowest recurrence rate, especially those without lymphovascular invasion. This study might aid the establishment of a standard therapy for CSI NSGCT in China.

Clinical features of probable severe acute respiratory syndrome in Beijing

AIM: To summarize clinical features of probable severe acute respiratory syndrome (SARS) in Beijing.METHODS: Retrospective cases involving 801 patients admitted to hospitals in Beijing between March and June 2003, with a diagnosis of probable SARS, moderate type.The series of clinical manifestation, laboratory and radiograph data obtained from 801 cases were analyzed. RESULTS: One to three days after the onset of SARS, the major clinical symptoms were fever (in 88.14% of patients), fatigue, headache, myalgia, arthralgia (25-36%), etc. The counts of WBC (in 22.56% of patients) lymphocyte (70.25%)and CD3, CD4, CD8 positive T cells (70%) decreased. From 4-7 d, the unspecific symptoms became weak; however, the rates of low respiratory tract symptoms, such as cough (24.18%), sputum production (14.26%), chest distress (21.04%) and shortness of breath (9.23%) increased, so did the abnormal rates on chest radiograph or CT. The low counts of WBC, lymphocyte and CD3, CD4, CD8 positiveT cells touched bottom. From 8 to 16 d, the patients presented progressive cough (29.96%), sputum production (13.09%), chest distress (29.96%) and shortness of breath (35.34%). All patients had infiltrates on chest radiograph or CT, some even with multi-infiltrates. Two weeks later, patients' respiratory symptoms started to alleviate, the infiltrates on the lung began to absorb gradually, the counts of WBC, lymphocyte and CD3, CD4, CD8 positive T cells were restored to normality.CONCLUSION: The data reported here provide evidence that the course of SARS could be divided into four stages, namely the initial stage, progressive stage, fastigium and convalescent stage.

Usefulness of staging systems and prognostic scores for hepatocellular carcinoma treatments

Therapeutic management of hepatocellular carcinoma(HCC) is quite complex owing to the underlying cirrhosis and portal vein hypertension. Different scores or classification systems based on liver function and tumoral stages have been published in the recent years. If none of them is currently "universally" recognized, the Barcelona Clinic Liver Cancer(BCLC) staging system has become the reference classification system in Western countries. Based on a robust treatment algorithm associated with stage stratification, it relies on a high level of evidence. However, BCLC stage B and C HCC include a broad spectrum of tumors but are only matched with a single therapeutic option. Some experts have thus suggested to extend the indications for surgery or for transarterial chemoembolization. In clinical practice, many patients are already treated beyond the scope of recommendations. Additional alternative prognostic scores that could be applied to any therapeutic modality have been recently proposed. They could represent complementary tools to the BCLC staging system and improve the stratification of HCC patients enrolled in clinical trials, as illustrated by the NIACE score. Prospective studies are needed to compare these scores and refine their role in the decision making process.

Comparative proteomic study of colorectal carcinoma with different clinical stages

Objective： Colorectal carcinoma clinical stage associated proteins would be found by comparing differential expressed proteins from colorectal carcinoma tissues with different clinical stages. Methods： Total protein from colorectal carcinoma tissues were extracted; differential proteome profiles were established and analyzed by means of immobilized pH gradient-based two-dimensional polyacrylamide gel electrophoresis （2-DE） and matrix-assisted laser desorption/ionization time of flight mass spectrometry （MALDI-TOF-MS）. Results： Well-resolved, reproducible 2-DE profiles of human colorectal carcinoma tissues were obtained. Average protein spots were 970 ± 41,980 ± 32, 1010 ± 43, 1240 ±34 in stage Ⅰ, stage Ⅱ, stage Ⅲ, stage Ⅳ respectively; Compared to stage Ⅰ, differential expressed protein spots was 52.00 ± 12 in stage Ⅱ, 42.00 ± 11 in stage Ⅲ, 72.00 ± 15 in stage Ⅳ; Part of differential expressing proteins were analyzed by mass spectrometry and bioinformation, 19 of them were well characterized. Three proteins were overexpressed in stage Ⅰ, stage Ⅲ, stage Ⅳ, and one protein were overexpressed in stage Ⅳ exclusively. Conclusion： Differential expressed proteins exist in clinical stage of colorectal carcinoma, which would be biomarkers for diagnosis and prediction of prognosis.

Relationship between C-reactive protein and clinical stage in nasopharyngeal carcinoma

Objective： The aim of our study was to explore the correlations between C-reactive protein （CRP） levels and clinical stages of nasopharyngeal carcinoma （NPC）. Methods： We analyzed 108 cases, among them, 68 cases were NPC, 20 cases were benign inflammatory diseases of nasopharynx, 20 cases were healthy volunteers as control. CRP was determined with immunoturbidimetry （ITM）. Results： The mean concentrations of CRP in NPC （19.76 rag/L） were significantly increased compared to that in the control group （6.23 mg/L）, while were significantly lower than that in benign inflammatory group （45.63 mg/L）; The mean concentrations of CRP in T4 group （25.58 mg/L） were higher than that in T1 group （17.35 mg/L）, T2 group （18.65 mg/L） and T3 group （15.61 mg/L）. The mean concentrations of CRP in N3 group （28.04 mg/L） were higher than that in NO （17.62mg/L）, N1 （21.27 mg/L）, N2 （18.62 mg/L） respectively, the mean concentrations of CRP in IV （25.74 mg/L） were higher than that in I （14.20 mg/L）, II （16.10 mg/L）, III （23.01 mg/L）, respectively. Conclusion： The serum CRP level is associated with the occurrence of NPC and benign inflammatory disease of nasopharynx. In NPC, the CRP level has positive relationship with the TNM stage.

Clinical Efficacy of Dasatinib in the Treatment of Chronic Myeloid Leukemia (CML) Patients with Different Clinical Stages

Objective:To study the efficacy of dasatinib treatment in different clinical stages of patients with chronic myeloid leukemia(CML).Methods:A total of 80 patients with chronic myeloid leukemia(CML)were selected for experimental research.According to different clinical stages,they were divided into chronic phase,accelerated phase and blast phase,and all of them were treated with dasatinib.Results:The complete cytogenetic response remission rate,complete hematologic remission rate,and major molecular biological remission rate in the chronic phase were significantly higher.Besides,the overall survival time and relapse-free survival time in the chronic phase were significantly longer,and the mortality during the follow-up period in the chronic phase was also significantly higher.Furthermore,the incidence of hematological adverse reactions of gradesⅢtoⅣin the chronic phase was significantly lower compared with the corresponding data of patients in the accelerated phase and blast phase with P<0.05.Conclusion:Different clinical stages of CML patients have different curative effects of dasatinib,which can effectively treat patients in chronic stage.

Impact of guideline adherence on the prognosis of Barcelona clinic liver cancer stage B hepatocellular carcinoma

BACKGROUND Patients with Barcelona clinic liver cancer(BCLC)stage B hepatocellular carcinoma(HCC)are considerably heterogeneous in terms of tumor burden,liver function,and performance status.To improve the poor survival outcomes of these patients,treatment approaches other than transarterial chemoembolization(TACE),which is recommended by HCC guidelines,have been adopted in realworld clinical practice.We hypothesize that this non-adherence to treatment guidelines,particularly with respect to the use of liver resection,improves survival in patients with stage B HCC.AIM To assess guideline adherence in South Korean patients with stage B HCC and study its impact on survival.METHODS A retrospective analysis was conducted using data from 2008 to 2016 obtained from the Korea Central Cancer Registry.Patients with stage B HCC were categorized into three treatment groups,guideline-adherent,upward,and downward,based on HCC guidelines recommended by the Asian Pacific Association for the Study of the Liver(APASL),the European Association for the Study of the Liver(EASL),and the American Association for the Study of Liver Diseases(AASLD).The primary outcome was HCC-related deaths;tumor recurrence served as the secondary outcome.Survival among the groups was compared using the Kaplan-Meier method and the log-rank test.Predictors of survival outcomes were identified using multivariable Cox regression analysis.RESULTS In South Korea, over the study period from 2008 to 2016, a notable trend was observed in adherence to HCCguidelines. Adherence to the EASL guidelines started relatively high, ranging from 77% to 80% between 2008 and2012, but it gradually declined to 58.8% to 71.6% from 2013 to 2016. Adherence to the AASLD guidelines began at71.7% to 75.9% from 2008 to 2010, and then it fluctuated between 49.2% and 73.8% from 2011 to 2016. In contrast,adherence to the APASL guidelines remained consistently high, staying within the range of 90.14% to 94.5%throughout the entire study period. Upward treatment, for example with liver resection, liver transplantation, orradiofrequency ablation, significantly improved the survival of patients with BCLC stage B HCC compared to thatof patients treated in adherence to the guidelines (for patients analyzed according to the 2000 EASL guidelines, the5-year survival rates were 63.4% vs 27.2%, P < 0.001), although results varied depending on the guidelines.Progression-free survival rates were also significantly improved upon the use of upward treatments in certaingroups. Patients receiving upward treatments were typically < 70 years old, had platelet counts > 105/μL, andserum albumin levels ≥ 3.5 g/dL.CONCLUSIONAdherence to guidelines significantly influences survival in South Korean stage B HCC patients. Curativetreatments outperform TACE, but liver resection should be selected with caution due to disease heterogeneity.

Expression of hepatic Wnt5a and its clinicopathological features in patients with hepatocellular carcinoma

Backgroud： Wingless-type MMTV integration site family member 5a （Wnt5a） is involved in carcinogenesis.However, little data are available in Wnt5a signaling with hepatocellular carcinoma （HCC）. In thepresent study, we investigated the expression of hepatic Wnt5a in HCC and the role of Wnt5a in HCCprogression and outcome.

Advances in diagnosis and treatment strategies of thymic carcinoid

Thymic carcinoid is a rare neuroendocrine tumor with unclear risk factors and controversial classifications. Its clinical manifestations vary from asymptomatic to many nonspecific symptoms,among which endocrine abnormality seems to be associated with poor prognosis. Quantitative and qualitative analysis of ACTH and prognosis could become a topic in the future. Image studies show no specificity both in CT and PET/CT,but are of great value in clinical staging of thymic carcinoid. Ki67 has been found to be a powerful tool for grading neuroendocrine tumors and further studies should be made. The diagnosis of thymic carcinoid mainly depends on pathology and immunohistochemistry plays a key role in differential diagnosis at present. Radical resection is the first choice in treatment,and target therapy becomes possible with the development in molecular pathology. However,since the rarity of thymic carcinoid,there is no practical clinical staging or standard guideline to instruct clinical practice. Thus,support of International Thymic Malignancy Interest Group( ITMIG) seems to be of great significance in case collection and resource sharing of thymic diseases. In this paper,we are going to put forward a strategy available in clinical application for diagnoisis and treatment of thymic carcinoid by using a new clinical staging system.

Novel methylation gene panel in adjacent normal tissues predicts poor prognosis of colorectal cancer in Taiwan

BACKGROUND It is evident that current clinical criteria are suboptimal to accurately estimate patient prognosis.Studies have identified epigenetic aberrant changes as novel prognostic factors for colorectal cancer(CRC).AIM To estimate whether a methylation gene panel in different clinical stages can reflect a different prognosis.METHODS We enrolled 120 CRC patients from Tri-Service General Hospital in Taiwan and used the candidate gene approach to select six genes involved in carcinogenesis pathways.Patients were divided into two groups based on the methylation status of the six evaluated genes,namely,the<3 aberrancy group and≥3 aberrancy group.Various tumor stages were divided into two subgroups(local and advanced stages)on the basis of the pathological type of the following tissues:Tumor and adjacent normal tissues(matched normal).We assessed DNA methylation in tumors and adjacent normal tissues from CRC patients and analyzed the association between DNA methylation with different cancer stages and the prognostic outcome including time to progression(TTP)and overall survival.RESULTS We observed a significantly increasing trend of hazard ratio as the number of hypermethylated genes increased both in normal tissue and tumor tissue.The 5-year TTP survival curves showed a significant difference between the≥3 aberrancy group and the<3 aberrancy group.Compared with the<3 aberrancy group,a significantly shorter TTP was observed in the≥3 aberrancy group.We further analyzed the interaction between CRC prognosis and different cancer stages(local and advanced)according to the methylation status of the selected genes in both types of tissues.There was a significantly shorter 5-year TTP for tumors at advanced stages with the promoter methylation status of selected genes than for those with local stages.We found an interaction between cancer stages and the promoter methylation status of selected genes in both types of tissues.CONCLUSION Our data provide a significant association between the methylation markers in normal tissues with advanced stage and prognosis of CRC.We recommend using these novel markers to assist in clinical decision-making.

Real impact of tumor marker AFP and PIVKA-II in detecting very small hepatocellular carcinoma(≤2 cm,Barcelona stage 0)-assessment with large number of cases

BACKGROUND In hepatocellular carcinoma(HCC),detection and treatment prior to growth beyond 2 cm are relevant as a larger tumor size is more frequently associated with microvascular invasion and/or satellites.AIM To examine the impact of the tumor marker alpha-fetoprotein(AFP)or PIVKA-II in detecting very small HCC nodules(≤2 cm in maximum diameter,Barcelona stage 0)in the large number of very small HCC.The difference in the behavior of these tumor markers in HCC development was also examined.METHODS A total of 933 patients with single-nodule HCC were examined.They were subdivided into 394 patients with HCC nodules≤2 cm in maximum diameter and 539 patients whose nodules were>2 cm.The rates of patients whose AFP and PIVKA-II showed normal values were examined.RESULTS The positive ratio of the marker PIVKA-II was significantly different(P<0.0001)between patients with nodules≤2 cm in diameter and those with nodules>2 cm,but there was no significant difference in AFP(P=0.4254).In the patients whose tumor was≤2 cm,50.5%showed normal levels in AFP and 68.8%showed normal levels in PIVKA-II.In 36.4%of those patients,both AFP and PIVKA-II showed normal levels.The PIVKA-II-positive ratio was markedly increased with an increase in the tumor size.In contrast,the positivity in AFP was increased gradually and slowly.CONCLUSION In the surveillance of very small HCC nodules(≤2 cm in diameter,Barcelona clinical stage 0)the tumor markers AFP and PIVKA-II are not so useful.