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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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Community-Based Mass Ultrasonographic Screening of Hepatocellular Carcinoma among Thrombocytopenic Adults

Sheng-Nan Lu, Jing-Houng Wang, Pao-Fei Chen, Hung-Da Tung, Po-Lin Tseng, Chao-Hung Hung, Kwong-Ming Kee, Chien-Hung Chen, Kuo-Chin Chang, Chuan-Mo Lee, Chi-Sin Changchien, Yao-Der Chen, Lin-San Tsai and Tony Hsiu-Hsi Chen
Sheng-Nan Lu
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Jing-Houng Wang
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Pao-Fei Chen
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Hung-Da Tung
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Po-Lin Tseng
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Chao-Hung Hung
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Kwong-Ming Kee
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Chien-Hung Chen
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Kuo-Chin Chang
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Chuan-Mo Lee
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Chi-Sin Changchien
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Yao-Der Chen
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Lin-San Tsai
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Tony Hsiu-Hsi Chen
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DOI: 10.1158/1055-9965.EPI-07-2746 Published July 2008
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  • Figure 1.
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    Figure 1.

    Right, Tainan county, located in southern Taiwan, comprised 31 townships; left, male mortality rates for HCC were >40/105 in 21 townships.

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    Figure 2.

    Flowchart of the community-based screening for HCC conducted in Tainan, Taiwan, 2004.

Tables

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  • Table 1.

    High-risk subjects' distribution and response rates to US by risk factors and viral etiology in the community-based screening for HCC in Tainan, Taiwan, 2004

    High-risk subjects, n (%)Responder to US, n (%)
    Total3,242 (100)2,983 (92.2)
    Risk factors
        Platelet count <150 × 109/L2,928 (90.3)2,697 (92.1)
        AFP >20 ng/mL87 (2.9)67 (77.0)
        Both227 (7.0)219 (79.1)
    Viral etiology
        HBsAg(+) alone465 (14.3)440 (94.6)
        Anti-HCV(+) alone1,291 (39.8)1,151 (89.2)
        Both123 (3.8)106 (86.2)
        Neither1,363 (42.1)1,286 (94.4)
  • Table 2.

    Distributions of responders by risk factors and viral etiology and confirmed HCC cases found in each group

    Risk factorsViral etiologyHBsAg(+), n (%)Anti-HCV(+), n (%)Both, n (%)Neither, n (%)Total, n (%)
    Platelet count <150 × 109/LReceived US390 (13.1)961 (32.2)87 (2.92)1,259 (42.2)2,697 (90.4)
    Confirmed3 (0.77)13 (1.35)2 (2.29)3 (0.24)21 (0.78)
    AFP >20 ng/mLReceived US18 (0.60)34 (1.14)4 (0.13)11 (0.37)67 (2.25)
    Confirmed6 (33.3)7 (20.6)2 (50.0)2 (18.2)17 (25.4)
    BothReceived US32 (1.07)156 (5.23)15 (0.50)16 (0.54)219 (7.34)
    Confirmed5 (15.6)27 (18.0)1 (6.67)1 (6.25)34 (15.5)
    TotalReceived US440 (14.8)1,151 (38.6)106 (3.55)1,286 (43.1)2,983 (100.0)
    Confirmed14 (3.18)47 (4.09)5 (4.72)6 (0.47)72 (2.41)
    Platelet + bothReceived US4221,1171021,2752,916
    Confirmed8 (1.90)40 (3.58)3 (2.94)4 (0.31)55 (1.89)
    AFP + bothReceived US501901927286
    Confirmed11 (22.0)34 (17.9)3 (15.8)3 (11.1)51 (17.8)
  • Table 3.

    Estimation of HCC detection rates using platelet count, AFP, or both as the tool of risk group identification

    Viral etiology(1)*
    (2)
    (3) = (2) ÷ (1)
    (4)
    (6) = (3) - (5)
    % Thrombocytopenia in HCC casesCases included by thrombocytopeniaEstimated HCC casesCases included by AFPCases included by thrombocytopenia or AFPEstimated undetected cases
    B4281911145 (26.3)
    C634063344716 (25.4)
    B + C5036351 (16.7)
    NBNC30413367 (53.8)
    Total, n (%)55 (54.5)101 (100)51 (50.5)72 (71.3)29 (28.7)
    • ↵* Ref. 20.

  • Table 4.

    Numbers of subjects and cases of primary liver cancer in variant screen status

    Status of two-staged HCC screeningNo. subjectsNo. cases
    Total screening cases56,702119
    (1) Low-risk group by first-stage screening53,46017
        High-risk group3,242102
    (2) Nonresponder to US25910
        Responder to US2,98392
    (3) Negative US results2,80415
        Known HCC cases4242
        Suspected cases13777
    (4) Refuse referral133
        Refer for confirmation12474
    (5) No definite malignancy by hospital522
        Confirmed HCC cases7272
  • Table 5.

    Cases of primary liver cancer found from National Cancer Registration Database by status of second-stage screening, periods and screening markers

    Status of second-stage screeningnPeriod*
    IIIIIITotal cases
    (2) Nonresponder to US2597 (1, 4, 2)†1 (0, 1, 0)2 (1, 1, 0)10 (2, 6, 2)
    (3) Negative US results2,80404 (1, 3, 0)11 (8, 3, 0)15 (9, 6, 0)
    (4) Refuse referral132 (0, 1, 1)01 (0, 0, 1)3 (0, 1, 2)
    (5) No definite malignancy by hospital521 (1, 0, 0)01 (1, 0, 0)2 (2, 0, 0)
    Total3,1281051530
    Platelet count <150 × 109/L211013
    AFP >20 ng/mL3014
    Both54413
    • ↵* Period I, during the screening (from April to December 2004); period II: within 6 months after the screening (from January to June 2005); and period III: between 7 and 12 months after the screening (from July to December 2005).

    • ↵† Number of cases with platelet count <150 × 109/L, number of cases with platelet count <150 × 109/L and AFP >20 ng/mL, number of cases with AFP >20 ng/mL.

  • Table 6.

    Validity of first-stage screening, second-stage screening, and the whole two-stage screening based on National Cancer Registration Database

    First-stage screening liver cancer
    Second-stage screening liver cancer
    Two-stage screening liver cancer
    (+)(-)Total(+)(-)Total(+)(-)Total
    Screening (+)1023,1403,24277601377760137
    Screening (-)1753,44353,460253,0803,1054256,52356,565
    Total11956,58356,7021023,1403,24211956,58356,702
    Sensitivity102/119 = 85.7%77/102 = 75.5%77/119 = 64.7%
    Specificity53,443/56,583 = 94.5%3,080/3,140 = 98.1%56,523/56,583 = 99.9%
    Accuracy53,545/56,702 = 94.4%3,157/3,242 = 97.4%56,600/56,702 = 99.8%
    PPV102/3,242 = 3.15%77/137 = 56.2%77/137 = 56.2%
    NPV53,443/53,460 = 99.97%3,080/3,105 = 99.2%56,523/56,565 = 99.9%
  • Table 7.

    Comparison among four two-stage community-based HCC screenings

    References*Model 1 (9)*Model 2 (10, 2, 15)*Model 3 (19)*Model 4
    First authorWu JCChen CJ, 1995Lu SNCurrent study
    Year published1988Chen TH, 2002 Yang HI, 20022006
    Sample size of screening1,894Male/female: 12,026/1,800(Low)† 1,694, (High)† 4,61656,702
    Screening makers in first stageAFPHBsAg, anti-HCV, AFP, aspartate aminotransferase, alanine aminotransferase, family historyPlatelet(A), (P), (B)‡
    % High-risk subjects identified from population1%Male/female: 30.9%/34.6%(Low) 6.1%, (High)17.9%(A) 0.64%, (P) 5.33%, (B) 5.70%
    Estimated sensitivity for HCC detectionNot available>90%48%(A) 50.5%, (P) 54.5%, (B) 71.3%
    Second-stage Screening toolsUS in hospitalUS in communityUS, AFP in communityUS in community
    PPV of first-stage marker(s)21%Not available(Low) 0%, (High) 4.27%17.8%, 1.89%, 2.41%
    Surveillance program for high-risk groupNilCirrhosis every 3 mo, others every 6 moNilLimited to HBsAg(+), anti-HCV(+), or cirrhosis
    • ↵* (9), Wu JC, Liver 1988; (10), Chen CJ, J Formosan Med Assoc 1995; (2), Chen THH, Int J Cancer 2002; (15), Yang HI, NEJM 2002; (18), Lu SN, Cancer 2006.

    • ↵† (Low) and (High), low and high prevalence areas of hepatitis C and hepatocellular carcinoma.

    • ↵‡ (A), AFP alone; (P), platelet count alone; (Both), combination of both AFP and platelet count.

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Cancer Epidemiology Biomarkers & Prevention: 17 (7)
July 2008
Volume 17, Issue 7
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Community-Based Mass Ultrasonographic Screening of Hepatocellular Carcinoma among Thrombocytopenic Adults
Sheng-Nan Lu, Jing-Houng Wang, Pao-Fei Chen, Hung-Da Tung, Po-Lin Tseng, Chao-Hung Hung, Kwong-Ming Kee, Chien-Hung Chen, Kuo-Chin Chang, Chuan-Mo Lee, Chi-Sin Changchien, Yao-Der Chen, Lin-San Tsai and Tony Hsiu-Hsi Chen
Cancer Epidemiol Biomarkers Prev July 1 2008 (17) (7) 1813-1821; DOI: 10.1158/1055-9965.EPI-07-2746

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Community-Based Mass Ultrasonographic Screening of Hepatocellular Carcinoma among Thrombocytopenic Adults
Sheng-Nan Lu, Jing-Houng Wang, Pao-Fei Chen, Hung-Da Tung, Po-Lin Tseng, Chao-Hung Hung, Kwong-Ming Kee, Chien-Hung Chen, Kuo-Chin Chang, Chuan-Mo Lee, Chi-Sin Changchien, Yao-Der Chen, Lin-San Tsai and Tony Hsiu-Hsi Chen
Cancer Epidemiol Biomarkers Prev July 1 2008 (17) (7) 1813-1821; DOI: 10.1158/1055-9965.EPI-07-2746
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