Displaying all 14 publications

  1. Lopez JB
    Clin Biochem Rev, 2005 Aug;26(3):65-79.
    PMID: 16450014
    Hepatocellular carcinoma (HCC) ranks fifth in frequency of cancers worldwide. The main aetiological factor is hepatitis B virus (HBV) although the importance of hepatitis C virus (HCV) is growing. The most important tumour marker for HCC is alpha-fetoprotein (AFP). The common method of screening high risk patients by AFP and ultrasonography has been shown to result in earlier detection and consequently more easily treatable tumours and longer survival. Proposed screening interval varies from once every 3 months to annually to "as indicated' but, most commonly, is once every 6 months. AFP is a fairly specific but insensitive marker for HCC. Sensitivity of HCC detection by blood markers is improved by combining various other markers with AFP. Of the other markers, the newer high sensitivity des-gamma-carboxy-prothrombin (DCP) has been found to be useful. In addition the AFP fractions L3, P4/5 and the +II band are highly specific for HCC. Among routinely assayed tumour markers in the laboratory, CA 125 is more sensitive for HCC than AFP but far less specific. Various other enzymes, isoenzymes, growth factors, adhesion molecules, other proteins such as interleukin-2 receptor (IL-2R), human cervical cancer oncogene protein (HCCR) and glypican-3 (GPC3), p15 and p16 hypermethylation and nitrite/nitrate ratio have been tested; some of these show promise but none is presently in routine use. The value of other newer markers such as the HBx protein that is produced by HBV, and what are thought to be specific proteins and signatures identified by proteomics remain to be determined.
  2. Lopez JB, Balasegaram M, Thambyrajah V
    Int. J. Biol. Markers, 1996 Jul-Sep;11(3):178-82.
    PMID: 8915714
    This study was undertaken to investigate whether serum CA 125 could complement alpha-fetoprotein (AFP) to improve the diagnosis of hepatocellular carcinoma (HCC). CA 125 showed a sensitivity of 92% for HCC against the 58.8% sensitivity of AFP at the cutoff value of 200 ng/ml. However, the former was less specific (48.5% versus 97.4%) in relation to benign liver diseases (BLD). CA 125 had a higher negative predictive value (NPV) of 84.6% compared to 69.2% for AFP; when both markers were combined, however, the NPV rose to 91.7%. Overall, AFP was more efficient than CA 125 for the diagnosis of HCC. While a positive AFP result was highly indicative of HCC, a negative result did not rule out the disease; however, negative AFP and CA 125 meant that the likelihood of the disease was low. In situations of low HCC prevalence, CA 125 could serve as a first-line screening test followed by confirmation of positives by AFP.
  3. Lopez JB, Peng CL
    Clin Chem Lab Med, 2003 Oct;41(10):1369-72.
    PMID: 14580168
    The concentration of homocysteine (Hcy) rises rapidly after the collection of blood. This feature requires blood to be collected into the anticoagulants EDTA or heparin and the plasma to then be immediately separated; alternatively, the blood may be kept on ice and centrifuged within 1 hour. The use of chemical preservatives has been proposed as a means of stabilising Hcy levels in whole blood after collection. The objective of this study was to determine whether the commonly available fluoride-oxalate (Fl-Ox) and sodium citrate (Na-Cit) containers could stabilise Hcy levels in blood. Our results showed that when blood was collected into potassium EDTA (K-EDTA) tubes, Hcy levels rose from initial levels, on standing at room temperature (approximately 25 degrees C), by an average of 21% after 3 hours and 32% after 5 hours. The initial Hcy levels of blood collected into Fl-Ox and Na-Cit containers, however, were lower, at averages of 89% and 91%, respectively, compared to that of the same samples when collected into K-EDTA tubes. Hcy in these samples subsequently rose on standing, and after 5 hours was, on the average, 10 and 13% higher, respectively, compared with the initial levels in K-EDTA tubes. We conclude that Fl-Ox and Na-Cit do not stabilise Hcy in blood after collection and should not be used as preservatives.
  4. Kamariah K, Lopez JB, Satgunasingam N
    Br J Biomed Sci, 1994 Sep;51(3):296-8.
    PMID: 7881328
    We assessed the analytical performance of the Abbott IMxTM immunoassay analyser for total beta human chorionic gonadotropin (Beta hCG), follicle-stimulating hormone (FSH) and luteinising hormone (LH). The within-run CVs for various analyte concentrations were 2% to 6% while those for between-run imprecision in routine assay ranged from 4% to 10%. IMxTM values correlated well with radioimmunoassay for beta hCG, and immunoradiometric assay for FSH and LH; the correlation coefficients (r) were 0.97, 0.99 and 0.98 for total beta hCG, FSH and LH respectively. The average sensitivities were approximately 3.1, 0.2 and 0.5 iu/l for beta hCG, FSH and LH, respectively. Sample carry-over was not detected and there was negligible cross-reaction between LH and beta hCG in the respective assays. The automatic sample dilution protocol for beta hCG was superior to the manual procedure. The IMxTM is easy to operate and is able to process 24 samples in 40-45 minutes.
  5. Lopez JB, Balasegaram M, Thambyrajah V, Timor J
    Malays J Pathol, 1996 Dec;18(2):95-9.
    PMID: 10879229
    This study was undertaken to see if liver function tests (LFT) served a worthwhile purpose in the investigation of hepatocellular carcinoma (HCC). Sera from 80 HCC, 76 benign liver disease (BLD) and 152 healthy adult (HA) subjects were assayed for alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase and lactate dehydrogenase, bilirubin and albumin. Cut-off values were determined from the HA. ALP, GGT, AST and albumin were abnormal in about 90% of the HCC. With the exception of bilirubin, the LFT were abnormal more frequently in HCC than in chronic hepatitis and cirrhosis, the conditions which preceed it. Raised ALP in the presence of normal bilirubin was more often a feature of HCC than BLD although this relationship was not statistically significant. It seems unlikely that LFT serve a useful function in HCC.
  6. Lopez JB, Balasegaram M, Timor J, Thambyrajah V
    Malays J Pathol, 1997 Jun;19(1):53-8.
    PMID: 10879242
    Although alpha-fetoprotein (AFP) is regarded as the reference marker for hepatocellular carcinoma (HCC), it sometimes produces false results. The objective of this study was to see if some of the readily available laboratory markers could complement AFP to improve the laboratory diagnosis of HCC. The markers tested and their sensitivities were: CA 125, 92%; ferritin, 71.3%; CA 19-9, 69.8%; beta-2-microglobulin (B2M), 53.3%; CA 72-4, 13.6%; and carcinoembryonic antigen (CEA), 10.6%. In comparison, AFP had a sensitivity of 58.8%. CA 72-4 and CEA (at the "tumour" cut-off level of 20 ng/ml) had specificities of 100%, and AFP, 97.4%. The specificities of the other markers were less impressive: CEA, 77.8% (at the cut-off level of 5 ng/ml); ferritin, 48.6%; CA 125, 48.5%; B2M, 39.6%; and CA 19-9, 37.3%. The efficiencies of the markers for HCC, which are based on the consideration of sensitivity and specificity together, were as follows: AFP, 77.6%; CA 125, 71.3%; ferritin, 60.5%; CA 19-9, 55.3; B2M, 46.9%; CEA, 40.8%; and CA 72-4, 34.5%. The receiver-operating characteristic plots confirmed AFP to be the most efficient marker for HCC. Nevertheless, it is proposed that CA 125 be combined with AFP for HCC screening because of their excellent sensitivity and specificity, respectively: a negative result for both, or even just CA 125 alone, would indicate that the disease is unlikely while a positive AFP (which would likely occur with a positive CA 125) would make its presence highly probable. A positive CA 125 and negative AFP would be equivocal for HCC. Other markers in combination with AFP are less useful.
  7. Lopez JB, Sahabudin RM, Chin LP
    Int. J. Biol. Markers, 2004 Apr-Jun;19(2):164-7.
    PMID: 15255551
    Increased concentrations of insulin-like growth factor I (IGF-I) and decreased insulin-like growth factor binding protein 3 (IGFBP-3) in serum have been proposed as markers of prostate cancer (CaP). The evidence for this, however, is contradictory. We assayed serum for IGF-I, IGFBP-3 and prostate-specific antigen (PSA) in patients with CaP and benign prostatic hyperplasia (BPH) and in healthy controls (HC). The mean +/- SD concentration of IGF-I in CaP (98.3 +/- 39.3 ng/mL; n = 15) was lower than in BPH (119 +/- 31.1 ng/mL; n=24) and HC (119 +/- 36.1 ng/mL; n=46), but the differences between the three groups were not statistically significant (p > 0.05). The mean IGFBP-3 concentrations in CaP (2691 +/- 1105 ng/mL; n = 16; p = 0.029) and BPH (2618 +/- 816 ng/mL; n = 26; p = 0.006) patients were significantly lower than that of the HC (3119 +/- 618 ng/mL; n=59), but the difference between the two groups of patients was not significant (p > 0.05). PSA concentrations in CaP (median = 80.8 ng/mL; n = 25) were significantly higher than those in BPH (median = 8.6 ng/mL; n = 39) (p < 0.001). Ninety-six percent of CaP and 72% of BPH patients had PSA concentrations >4.0 ng/mL; the proportions of patients with concentrations exceeding 20 ng/mL were 76% and 10%, respectively. We conclude that IGF-I and IGFBP-3 are inferior to PSA for CaP detection.
  8. Gammie AJ, Lopez JB, Scott S
    Clin Chem Lab Med, 2023 Mar 28;61(4):634-637.
    PMID: 36343330 DOI: 10.1515/cclm-2022-1052
    Clinical laboratories are significant contributors to the environmental burden of the planet. They have been slow to address the issues with a few exceptions, but it is highly encouraging to see the current impetus and ambition in this direction. This paper describes some of these initiatives and provides the rationale as to why clinical laboratories should become sustainable. It also describes the economic and intangible benefits that labs will accrue in achieving sustainability.
  9. Lopez JB, Thambyrajah V, Balasegaram M, Satgunasingam N
    Br J Biomed Sci, 1994 Jun;51(2):177-80.
    PMID: 7519505
    Sera from 80 Malaysians with confirmed hepatocellular carcinoma were tested for five markers of the hepatitis B virus, anti-HCV and anti-HDV by enzyme immunoassay, and alpha fetoprotein (AFP) was measured by radioimmunoassay. Of the patients, 98.8% had evidence of HBV infection and 75% were positive for HBsAg--which latter correlated with AFP raised above cut-off values of 500 ng/ml (P = 0.0001) and 200 ng/ml (P = 0.005). Males correlated significantly with the presence of HBsAg (P = 0.002). Thirty-one per cent of HBsAg positive patients were also positive for HBeAg and 74% for anti-HBe. Twenty per cent of the cases were concurrently positive for both HBsAg and anti-HBs. Six of 70 (8.6%) patients were positive for anti-HCV, of whom four were also positive for HBsAg. None of 67 patients tested for anti-HDV were positive. The results strongly indicate an important aetiological role for hepatitis B virus in causation of hepatocellular carcinoma among Malaysians.
  10. Lopez JB, Royan GP, Lakhwani MN, Mahadaven M, Timor J
    Int. J. Biol. Markers, 1999 Jul-Sep;14(3):172-7.
    PMID: 10569140
    The objective of this study was to compare CA 72-4 with CEA and CA 19-9 in gastrointestinal malignancies. CA 72-4 was assayed by radioimmunoassay and CEA and CA 19-9 with the Abbott IMx analyser. The study included 52 patients with gastrointestinal cancer and 20 controls with benign gastrointestinal diseases. The 52 cases showed marker sensitivities of 39%, 49% and 35% for CA 72-4, CEA and CA 19-9, respectively, and 64% when the markers were combined. Marker expression in serum was highest in colorectal carcinoma followed by gastric and esophageal carcinoma. The sensitivities of the individual markers in colorectal, gastric and esophageal carcinomas, respectively, were: CA 72-4, 56%, 32% and 18%; CEA, 83%, 33% and 18%; CA 19-9, 53%, 25% and 18%. The sensitivity of the three markers in combination was 89%, 50% and 46% in colorectal, gastric and esophageal cancer, respectively. The specificity of CA 72-4, CEA and CA 19-9 was 100%, 72% and 86%, respectively. However, CA 72-4 is not a useful a marker for gastrointestinal cancers because of its poor sensitivity. CEA, which had the best overall sensitivity and a reasonable specificity, was the most useful single marker, especially for colorectal cancer. Whereas the single markers were not useful in gastric and esophageal cancer, the combination of the three may be.
  11. Lopez JB, Jackson D, Gammie A, Badrick T
    Clin Biochem Rev, 2017 Feb;38(1):3-11.
    PMID: 28798502
    Healthcare is a significant contributor to environmental impact but this has received little attention. The typical laboratory uses far more energy and water per unit area than the typical office building. There is a need to sensitise laboratories to the importance of adopting good environmental practices. Since this comes at an initial cost, it is vital to obtain senior management support. Convincing management of the various tangible and intangible benefits that can accrue in the long run should help achieve this support. Many good environmental practices do not have a cost but will require a change in the culture and mind-set of the organisation. Continuing education and training are important keys to successful implementation of good practices. There is a need to undertake a rigorous cost-benefit analysis of every change that is introduced in going green. The adoption of good practices can eventually lead to ISO certification if this is desired. This paper provides suggestions that will allow a laboratory to start going green. It will allow the industry to enhance its corporate citizenship whilst improving its competitive advantage for long-term.
  12. Shiesh SC, Wiedmeyer HM, Kao JT, Vasikaran SD, Lopez JB, Laboratory Management Committee for the Asian-Pacific Federation of Clinical Biochemistry
    Clin Chem, 2009 Oct;55(10):1876-80.
    PMID: 19617287 DOI: 10.1373/clinchem.2009.129726
    BACKGROUND: The correlation between hemoglobin A(1c) (Hb A(1c)) and risk for complications in diabetic patients heightens the need to measure Hb A(1c) with accuracy. We evaluated the current performance for measuring Hb A(1c) in the Asian and Pacific region by examining data submitted by laboratories participating in the Taiwan proficiency-testing program.

    METHODS: Five fresh-pooled blood samples were sent to participating laboratories twice each year. The results were evaluated against target values assigned by the National Glycohemoglobin Standardization Program network laboratories; a passing criterion of +/-7% of the target value was used. Measurement uncertainty at Hb A(1c) concentrations of 7.0% and 8.0% were determined.

    RESULTS: A total of 276 laboratories from 11 countries took part in the Hb A(1c) survey. At the Hb A(1c) concentrations tested method-specific interlaboratory imprecision (CVs) were 1.1%-13.9% in 2005, 1.3%-10.1% in 2006, 1.2%-8.2% in 2007, and 1.1%-6.1% in 2008. Differences between target values and median values from the commonly used methods ranged from -0.24% to 0.22% Hb A(1c) in 2008. In 2005 83% of laboratories passed the survey, and in 2008 93% passed. At 7.0% Hb A(1c), measurement uncertainty was on average 0.49% Hb A(1c).

    CONCLUSIONS: The use of accuracy-based proficiency testing with stringent quality criteria has improved the performance of Hb A(1c) testing in the Asian and Pacific laboratories during the 4 years of assessment.

  13. Lai LC, Cheong SK, Goh KL, Leong CF, Loh CS, Lopez JB, et al.
    Malays J Pathol, 2003 Dec;25(2):83-105.
    PMID: 16196365
    Tumour markers are substances related to the presence or progress of a tumour. An ideal tumour marker is (1) detectable only when malignancy is present, (2) specific for the type and site of malignancy, (3) correlates with the amount of malignant tissue present and (4) responds rapidly to a change in tumour size. At present, no tumour marker fulfills all of the above criteria. The first part of the review discusses the clinical usefulness of the commonly requested serum tumour markers, namely, prostate-specific antigen (PSA), CA 19-9, carcinoembryonic antigen (CEA), CA 125, CA 15-3, human chorionic gonadotrophin (hCG) and alpha-foetoprotein (AFP). It is hoped that this review article will decrease the abuse and misuse of these commonly requested serum tumour markers. The second part of the review discusses the clinical usefulness of catecholamines and their metabolites, calcitonin, thyroglobulin, parathyroid hormone, prolactin, adrenocorticotrophic hormone, oestrogen and progesterone receptors, p53, HER-2/c-erbB2, BRCA1 and BRCA2.
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