Displaying publications 21 - 40 of 63 in total

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  1. Ling YS, Lim LR, Yong YS, Tamin O, Puah PY
    Nat Prod Res, 2020 Jun;34(12):1796-1803.
    PMID: 30587039 DOI: 10.1080/14786419.2018.1531288
    Soft coral, Sinularia sp. had been proven to inherit promising anti-cancer properties against variety of cancer. Current study, Sinularia sp. extract was introduced to Hepatocellular carcinoma (Hep 3B). Cell viability assay indicated the extract exhibit a dose and time dependent cytotoxicity. LC50 exhibited the lowest at 72 h post treatment estimated as 45.3 µg/mL. Morphological alterations including nuclear condensation, cytoplasm shrinkage and deformed cellular shape in treated Hep 3B were observable. Chemometric analysis revealed hydrophobic metabolites were significantly altered. Elevated vitamin D and derivatives tend to up-regulation Ca2+ and ROS subsequently triggering apoptosis. Dysregulated glycerolipids may suggest that they were biotransformed to compensate the needs of phospholipids during cell damage. Perturbation of sphingolipids, ceramide and carbohydrate-conjugated ceramides species increased the release of pro-apoptotic components reside within mitochondria and promote programmed cell death in treated Hep 3B. To conclude, MS-based metabolomics enabled the characterization of Sinularia sp. extract-induced cell death.
    Matched MeSH terms: Liver Neoplasms/pathology*
  2. Primrose JN
    Med J Malaysia, 2005 Jul;60 Suppl B:67-9.
    PMID: 16108177
    Matched MeSH terms: Liver Neoplasms/pathology
  3. Sumithran E, Prathap K
    Cancer, 1977 Oct;40(4):1618-20.
    PMID: 198100
    Necropsy and clinical data show that primary hepatocellular carcinoma (PHC) is the commonest cancer among the Senoi (a Malaysian aboringine group). The other aboringine tribes do not appear to have this high predilection for liver cancer. In the necropsy series, PHS was present in 10 out of 22 Senoi patients with cirrhosis. All the 22 livers contained hepatocytes that stained with Shikata's orcein stain and specific immunoperoxidase and immunofluorescent stains for hepatitis B antigen (HBAg). This observation raises the strong possibility that hepatitis B may be an important etiologic factor in the development of cirrhosis and PHC in the Senoi. The reason for the high susceptibility of the Senoi for HB virus infection is not clear, and the role of aflatoxin in the pathogenesis of PHC in the Senoi has yet to be determined. That the Senoi are a numerically small community, maintaining their own unique dietary and social customs and living in readily accessible areas in the Malaysian jungle, makes them an ideal population for the study of factors in the etiology of liver cancer.
    Matched MeSH terms: Liver Neoplasms/pathology
  4. Handayani T, Sakinah S, Nallappan M, Pihie AH
    Anticancer Res, 2007 Mar-Apr;27(2):965-71.
    PMID: 17465228
    Xanthorrhizol is a sesquiterpenoid compound extracted from the rhizome of Curcuma xanthorrhiza. This study investigated the antiproliferative effect and the mechanism of action of xanthorrhizol on human hepatoma cells, HepG2, and the mode of cell death. An antiproliferative assay using methylene blue staining revealed that xanthorrhizol inhibited the proliferation of the HepG2 cells with a 50% inhibition of cell growth (IC50) value of 4.17 +/- 0.053 microg/ml. The antiproliferative activity of xanthorrhizol was due to apoptosis induced in the HepG2 cells and not necrosis, which was confirmed by the Tdt-mediated dUTP nick end labeling (TUNEL) assay. The xanthorrhizol-treated HepG2 cells showed typical apoptotic morphology such as DNA fragmentation, cell shrinkage and elongated lamellipodia. The apoptosis mediated by xanthorrhizol in the HepG2 cells was associated with the activation of tumor suppressor p53 and down-regulation of antiapoptotic Bcl-2 protein expression, but not Bax. The levels of Bcl-2 protein expression decreased 24-h after treatment with xanthorrhizol and remained lower than controls throughout the experiment, resulting in a shift in the Bax to Bcl-2 ratio thus favouring apoptosis. The processing of the initiator procaspase-9 was detected. Caspase-3 was also found to be activated, but not caspase-7. Xanthorrhizol exerts antiproliferative effects on HepG2 cells by inducing apoptosis via the mitochondrial pathway.
    Matched MeSH terms: Liver Neoplasms/pathology
  5. Yap SF, Peh SC
    Malays J Pathol, 1991 Dec;13(2):115-8.
    PMID: 1726642
    Serum alpha-fetoprotein (AFP) levels and its expression in liver tissue was studied in 50 cases of histologically confirmed hepatocellular carcinoma (HCC). Serum AFP levels were elevated (greater than 20iu/ml) in 35/50 (70%) of the cases, 28 of whom had levels greater than 500 iu/ml, which is highly suggestive of HCC. These results indicate that serum AFP, by itself, is a relatively insensitive diagnostic test for HCC. Although elevated levels in high risk patients provide a specific clue, a negative result does not exclude the diagnosis of HCC. Expression of AFP by tumour cells paralleled that of serum in the majority of cases. However, tissue AFP was negative in 7 patients who had markedly elevated serum AFP. This observation may be a reflection of preferential excretion of the tumour antigen or differential expression of the antigen by the tumour cells. None of the patients with normal serum AFP demonstrated a reaction for tissue AFP. There was no correlation between AFP production and tumour differentiation.
    Matched MeSH terms: Liver Neoplasms/pathology
  6. Yeoh NT, Somasundaram K, Alhady SF, Paramsothy M
    Med J Malaysia, 1986 Dec;41(4):365-9.
    PMID: 2823084
    Carcinoma of the biliary tract is a rare complication of choledochal cysts. Furthermore, the greater predisposition of the cyst wall to neoplastic change has been cited as additional justification for cyst excision rather than on-site internal drainage as the primary choice of operation. The report concerns a patient who developed cholangiocarcinoma despite excision of a choledochal cyst and presented with symptoms of biliary obstruction within one year of the operation. Although this is a rare complication, the need for careful long-term follow-up is supported by this observation.
    Matched MeSH terms: Liver Neoplasms/pathology
  7. Norsa'adah B, Nurhazalini-Zayani CG
    Asian Pac J Cancer Prev, 2013;14(11):6955-9.
    PMID: 24377632
    The incidence of hepatocellular carcinoma (HCC) is relatively high in Southeast Asia. Globally, HCC has a high fatality rate and short survival. The objectives of this retrospective cohort study were to review the epidemiology and survival of HCC patients at a tertiary centre in north-east of Peninsular Malaysia. Subjects were adult HCC patients diagnosed by histopathology or radio-imaging. Secondary liver carcinoma was excluded. Kaplan Meier and multiple Cox proportional hazard survival analyses were used. Only 210 HCC cases from years 1987-2008, were included in the final analysis. The number of cases was increasing annually. The mean age was 55.0 (SD 13.9) years with male:female ratio of 3.7:1. Approximately 57.6% had positive hepatitis B virus, 2.4% hepatitis C virus, 20% liver cirrhosis and 8.1% chronic liver disease. Only 2.9% had family history and 9.0% had frequently consumed alcohol. Most patients presented with abdominal pain or discomfort and had hepatomegaly, 47.9% had an elevated α-fetoprotein level of 800 IU/ml or more, 51.9% had multiple tumors and 44.8% involved multiple liver lobes. Approximately 63.3% were in stage 3 and 23.4% in stage 4, and 82.9% did not receive any treatment. The overall median survival time was 1.9 months (95% confidence interval (CI): 1.5, 2.3). The 1-month, 6-month, 1-year and 2-year survival rates were 71.8%, 23.3%, 13.0% and 7.3% respectively. Significant prognostic factors were Malay ethnicity [Adjusted hazard ratio (AHR) 1.6; 95%CI: 1.0, 2.5; p=0.030], no chemotherapy [AHR 1.7; 95%CI: 1.1, 2.5; p=0.017] and Child-Pugh class C [AHR 2.6; 95%CI: 1.4, 4.9; p=0.002]. HCC in our study affected a wide age range, mostly male, in advanced stage of disease, with no treatment and very low survival rates. Primary prevention should be advocated in view of late presentation and difficulty of treatment. Vaccination of hepatitis virus and avoidance of liver toxins are to be encouraged.
    Matched MeSH terms: Liver Neoplasms/pathology
  8. Khaw KY, Kumar P, Yusof SR, Ramanathan S, Murugaiyah V
    Arch Pharm (Weinheim), 2020 Nov;353(11):e2000156.
    PMID: 32716578 DOI: 10.1002/ardp.202000156
    α-Mangostin has been reported to possess a broad range of pharmacological effects including potent cholinesterase inhibition, but the development of α-mangostin as a potential lead compound is impeded by its toxicity. The present study investigated the impact of simple structural modification of α-mangostin on its cholinesterase inhibitory activities and toxicity toward neuroblastoma and liver cancer cells. The dialkylated derivatives retained good acetylcholinesterase (AChE) inhibitory activities with IC50 values between 4.15 and 6.73 µM, but not butyrylcholinesterase (BChE) inhibitory activities, compared with α-mangostin, a dual inhibitor (IC50 : AChE, 2.48 µM; BChE, 5.87 µM). Dialkylation of α-mangostin produced AChE selective inhibitors that formed hydrophobic interactions at the active site of AChE. Interestingly, all four dialkylated derivatives of α-mangostin showed much lower cytotoxicity, being 6.4- to 9.0-fold and 3.8- to 5.5-fold less toxic than their parent compound on neuroblastoma and liver cancer cells, respectively. Likewise, their selectivity index was higher by 1.9- to 4.4-fold; in particular, A2 and A4 showed improved selectivity index compared with α-mangostin. Taken together, modification of the hydroxyl groups of α-mangostin at positions C-3 and C-6 greatly influenced its BChE inhibitory and cytotoxic but not its AChE inhibitory activities. These dialkylated derivatives are viable candidates for further structural modification and refinement, worthy in the search of new AChE inhibitors with higher safety margins.
    Matched MeSH terms: Liver Neoplasms/pathology
  9. Chaudhry GE, Sohimi NKA, Mohamad H, Zafar MN, Ahmed A, Sung YY, et al.
    Asian Pac J Cancer Prev, 2021 Feb 01;22(S1):17-24.
    PMID: 33576208 DOI: 10.31557/APJCP.2021.22.S1.17
    OBJECTIVE: Liver cancer is one of the most common causes of cancer death, with reduced survival rates. The development of new chemotherapeutic agents is essential to find effective cytotoxic drugs that give minimum side effects to the surrounding healthy tissues. The main objective of the present study was to evaluate the cytotoxic effects and mechanism of cell death induced by the crude and diethyl ether extract of Xylocarpus mouccensis on the human hepatocellular carcinoma cell line.

    METHODS: The cytotoxicity activity was measured using the MTS assay. The mode of cell death determined by the apoptosis study, DNA fragmentation analysis done by using the TUNEL system. The pathway study or mechanism of apoptosis observed by study caspases 8, 9, 3/7 Glo-caspases method.

    RESULTS: In this study, the methanol extracts prepared from leaf Xylocarpus mouccensis leaf produced cytotoxicity effect with IC50 (72hr) < 30µg/ml. The IC50 value at 72 hours exerted by diethyl ether extract of Xylocarpus moluccensis leaf was 0.22 µg/ml, which was more cytotoxic than to that of crude methanol extract. The results obtained by the colorimetric TUNEL system suggest that methanol crude extract of Xylocarpus moluccensis (leaf), diethyl ether extract of Xylocarpus moluccensis (leaf) and methanol extract of Xylocarpus granatum (bark) induced DNA fragmentation in the HepG2 cell line. Besides, the caspase-Glo assay demonstrated that diethyl ether leaf extract of Xylocarpus moluccensis triggered apoptotic cell death via activation of caspases -8, and -3/7 However, no visible activation was noticed for caspase -9. Furthermore, TLC indicates the presence of potential metabolites in an extract of Xylocarpus moluccensis.

    CONCLUSION: Thus, the present study suggests the remarkable potential of active metabolites in the extract of Xylocarpus moluccensis as a future therapeutic agent for the treatment of cancer.
    .

    Matched MeSH terms: Liver Neoplasms/pathology*
  10. Mohd Azamai ES, Sulaiman S, Mohd Habib SH, Looi ML, Das S, Abdul Hamid NA, et al.
    J Zhejiang Univ Sci B, 2009 Jan;10(1):14-21.
    PMID: 19198018 DOI: 10.1631/jzus.B0820168
    Chlorella vulgaris (CV) has been reported to have antioxidant and anticancer properties. We evaluated the effect of CV on apoptotic regulator protein expression in liver cancer-induced rats. Male Wistar rats (200~250 g) were divided into eight groups: control group (normal diet), CDE group (choline deficient diet supplemented with ethionine in drinking water to induce hepatocarcinogenesis), CV groups with three different doses of CV (50, 150, and 300 mg/kg body weight), and CDE groups treated with different doses of CV (50, 150, and 300 mg/kg body weight). Rats were sacrificed at various weeks and liver tissues were embedded in paraffin blocks for immunohistochemistry studies. CV, at increasing doses, decreased the expression of anti-apoptotic protein, Bcl-2, but increased the expression of pro-apoptotic protein, caspase 8, in CDE rats, which was correlated with decreased hepatocytes proliferation and increased apoptosis as determined by bromodeoxy-uridine (BrdU) labeling and terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) assay, respectively. Our study shows that CV has definite chemopreventive effect by inducing apoptosis via decreasing the expression of Bcl-2 and increasing the expression of caspase 8 in hepatocarcinogenesis-induced rats.
    Matched MeSH terms: Liver Neoplasms/pathology*
  11. Tajul Arifin K, Sulaiman S, Md Saad S, Ahmad Damanhuri H, Wan Ngah WZ, Mohd Yusof YA
    BMC Cancer, 2017 12 21;17(1):879.
    PMID: 29268718 DOI: 10.1186/s12885-017-3883-3
    BACKGROUND: Chlorella vulgaris (ChV), a unicellular green algae has been reported to have anticancer and antioxidant effects. The aim of this study was to determine the chemopreventive effect of ChV on liver cancer induced rats by determining the level and expression of several liver tumour markers.

    METHODS: Male Wistar rats (200-250 g) were divided into 4 groups according to the diet given: control group (normal diet), ChV group with three different doses (50, 150 and 300 mg/kg body weight), liver cancer- induced group (choline deficient diet + 0.1% ethionine in drinking water or CDE group), and the treatment group (CDE group treated with three different doses of ChV). Rats were killed at 0, 4, 8 and 12 weeks of experiment and blood and tissue samples were taken from all groups for the determination of tumour markers expression alpha-fetoprotein (AFP), transforming growth factor-β (TGF-β), M2-pyruvate kinase (M2-PK) and specific antigen for oval cells (OV-6).

    RESULTS: Serum level of TGF-β increased significantly (p < 0.05) in CDE rats. However, ChV at all doses managed to decrease (p < 0.05) its levels to control values. Expressions of liver tumour markers AFP, TGF-β, M2-PK and OV-6 were significantly higher (p < 0.05) in tissues of CDE rats when compared to control showing an increased number of cancer cells during hepatocarcinogenesis. ChV at all doses reduced their expressions significantly (p < 0.05).

    CONCLUSIONS: Chlorella vulgaris has chemopreventive effect by downregulating the expression of tumour markers M2-PK, OV-6, AFP and TGF-β, in HCC-induced rats.

    Matched MeSH terms: Liver Neoplasms/pathology
  12. Taha MM, Abdul AB, Abdullah R, Ibrahim TA, Abdelwahab SI, Mohan S
    Chem Biol Interact, 2010 Aug 05;186(3):295-305.
    PMID: 20452335 DOI: 10.1016/j.cbi.2010.04.029
    Zerumbone (ZER), a monosesquiterpene found in the subtropical ginger (Zingiber zerumbet Smith), possesses antiproliferative properties to several cancer cells lines, including the cervical, skin and colon cancers. In this study, the antitumourigenic effects of ZER were assessed in rats induced to develop liver cancer with a single intraperitoneal injection of diethylnitrosamine (DEN, 200 mg/kg) and dietary 2-acetylaminofluorene (AAF) (0.02%). The rats also received intraperitoneal ZER injections at 15, 30 or 60 mg/kg body wt. twice a week for 11 weeks, beginning week four post-DEN injection. The hepatocytes of positive control (DEN/AAF) rats were smaller with larger hyperchromatic nuclei than normal, showing cytoplasmic granulation and intracytoplasmic violaceous material, which were characteristics of hepatocarcinogenesis. Histopathological evaluations showed that ZER protects the rat liver from the carcinogenic effects of DEN and AAF. Serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (AP) and alpha-fetoprotein (AFP) were significantly lower (P<0.05) in ZER-treated than untreated rats with liver cancer. The liver malondialdehyde (MDA) concentrations significantly (P<0.05) increased in the untreated DEN/AAF rats indicating hepatic lipid peroxidation. There was also significant (P<0.05) reduction in the hepatic tissue glutathione (GSH) concentrations. The liver sections of untreated DEN/AAF rats also showed abundant proliferating cell nuclear antigen (PCNA), while in ZER-treated rats the expression of this antigen was significantly (P<0.05) lowered. By the TUNEL assay, there were significantly (P<0.05) higher numbers of apoptotic cells in DEN/AAF rats treated with ZER than those untreated. Zerumbone treatment had also increased Bax and decreased Bcl-2 protein expression in the livers of DEN/AAF rats, which suggested increased apoptosis. Even after 11 weeks of ZER treatment, there was no evidence of abnormality in the liver of normal rats. This study suggests that ZER reduces oxidative stress, inhibits proliferation, induces mitochondria-regulated apoptosis, thus minimising DEN/AAF-induced carcinogenesis in rat liver. Therefore, ZER has great potential in the treatment of liver cancers.
    Matched MeSH terms: Liver Neoplasms/pathology
  13. Katiman D, Manikam J, Goh KL, Abdullah BJ, Mahadeva S
    J Gastrointest Cancer, 2012 Sep;43 Suppl 1:S187-90.
    PMID: 22692948 DOI: 10.1007/s12029-012-9373-6
    Matched MeSH terms: Liver Neoplasms/pathology
  14. Abdul Hakim MS, Azmi AN, Jayalakshmi P, Mahadeva S
    J Gastrointest Cancer, 2018 Sep;49(3):346-348.
    PMID: 28066868 DOI: 10.1007/s12029-016-9913-6
    Matched MeSH terms: Liver Neoplasms/pathology*
  15. Mun KS, Cheah PL, Baharudin NB, Looi LM
    Malays J Pathol, 2006 Dec;28(2):73-7.
    PMID: 18376794 MyJurnal
    Hepatocellular carcinoma (HCC) is among the ten most common cancers in Malaysian males. As cellular proliferation is an important feature of malignant transformation, we studied the proliferation pattern of normal and benign perineoplastic liver versus hepatocellular carcinoma in an attempt to further understand the tumour transformation process. 39 HCC (21 with accompanying and 18 without cirrhosis) histologically diagnosed at the Department of Pathology, University of Malaya Medical Centre between January 1992 and December 2003 were immunohistochemically studied using a monoclonal antibody to PCNA (Clone PC10: Dako). 20 livers from cases who had succumbed to traumatic injuries served as normal liver controls (NL). PCNA labeling index (PCNA-LI) was determined by counting the number of immunopositive cells in 1000 contiguous HCC, benign cirrhotic perineoplastic liver (BLC), benign perineoplastic non-cirrhotic (BLNC) and NL cells and conversion to a percentage. The PCNA-LI was also expressed as Ojanguren et al's grades. PCNA was expressed in 10% NL, 38.9% BLNC, 76.2% BLC and 71.8% HCC with BLNC, BLC and HCC showing significantly increased (p < 0.05) number of cases which expressed PCNA compared with NL. The number of BLC which expressed PCNA was also significantly increased compared with BLNC. PCNA-LI ranged from 0-2.0% (mean = 0.2%) in NL, 0-2.0% (mean = 0.3%) in BLNC, 0-3.6% (mean = 0.7%) in BLC and 0-53.8% (mean = 7.6%) in HCC with PCNA-LI significantly increased (p < 0.05) only in HCC compared with BLC, BLNC and NL. Accordingly, all NL, BLC and BLNC showed minimal (<5% cells being immunopositive) immunoreactivity on Ojanguren et al's grading system and only HCC demonstrated immunoreactivity which ranged up to grade 3 (75% of cells). From this study, there appears to be a generally increasing trend of proliferative activity from NL to BLNC to BLC and HCC. Nonetheless, BLNC and BLC, like NL, retained low PCNA-LI and only HCC had a significantly increased PCNA-LI compared with the benign categories. This is probably related to the malignant nature of HCC and may reflect the uncontrolled proliferation of the neoplastic hepatocytes.
    Matched MeSH terms: Liver Neoplasms/pathology
  16. Sumithran E, Looi LM
    Cancer, 1985 Sep 1;56(5):1124-7.
    PMID: 2990666
    In West Malaysia, hepatocellular carcinoma (HCC) is common in the Chinese and in the members of the Senoi aboriginal tribe, two racial groups with diametrically opposite life-styles. Certain fundamental differences exist between the liver tumors in the two races. In the Senoi, the tumor occurs in a younger age group and there is a greater male preponderance than in the Chinese. There is also a very close relationship between hepatitis B virus infection, chronic active hepatitis, cirrhosis, liver cell dysplasia, and HCC in the Senoi and the tumors generally present as multiple nodules studding both lobes of the liver. In the Chinese, although a relationship between hepatitis B virus infection, HCC, and cirrhosis exists, this association is not as strong as in the Senoi and the tumors are generally large and solitary. The data suggest that, although the hepatitis B virus is probably an important oncogenic agent in both racial groups, there may be a difference in the pathogenesis of HCC in the two races.
    Matched MeSH terms: Liver Neoplasms/pathology*
  17. Ling LL, Hsu CC, Yong CC, Elsarawy AM, Chan YC, Wang CC, et al.
    Int J Surg, 2019 Sep;69:124-131.
    PMID: 31386913 DOI: 10.1016/j.ijsu.2019.07.035
    BACKGROUND: Tumor histology affects outcome after liver transplantation (LT) for hepatocellular carcinoma (HCC). This study explores the association between F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and tumor histology in living donor liver transplantation (LDLT) recipients and their outcome.

    MATERIALS AND METHODS: Two hundred fifty-eight patients with primary liver tumors who underwent FDG-PET before LDLT were enrolled in this retrospective study. Unfavorable tumor histology was defined as primary liver tumor other than a well- or moderately differentiated HCC. Thirteen patients had unfavorable tumor histology, including 2 poorly differentiated HCC, 2 sarcomatoid HCC, 5 combined hepatocellular cholangiocarcinoma, 3 intrahepatic cholangiocarcinoma, and 1 hilar cholangiocarcinoma.

    RESULTS: FDG-PET positivity was significantly associated with unfavorable tumor histology (P < 0.001). Both FDG-PET positivity and unfavorable tumor histology were significant independent predictors of tumor recurrence and overall survival. In a subgroup analysis of patients with FDG-PET-positive tumors, unfavorable tumor histology was a significant independent predictor of tumor recurrence and overall survival. High FDG uptake (tumor to non-tumor uptake ratio ≥ 2) was a significant predictor of unfavorable tumor histology. Patients with high FDG uptake and/or unfavorable tumors had significantly higher 3-year cumulative recurrence rate (70.8% versus 26.2%, P = 0.004) and worse 3-year overall survival (34.1% versus 70.8%, P = 0.012) compared to those with low FDG uptake favorable tumors.

    CONCLUSIONS: The expression of FDG-PET is highly associated with histology of explanted HCC and predicts the recurrence. FDG-PET-positive tumors with high FDG uptake may be considered contraindication for LDLT due to high recurrence rate except when pathology proves favorable histology.

    Matched MeSH terms: Liver Neoplasms/pathology
  18. Tak WY, Lin SM, Wang Y, Zheng J, Vecchione A, Park SY, et al.
    Clin Cancer Res, 2018 01 01;24(1):73-83.
    PMID: 29018051 DOI: 10.1158/1078-0432.CCR-16-2433
    Purpose: Lyso-thermosensitive liposomal doxorubicin (LTLD) consists of doxorubicin contained within a heat-sensitive liposome. When heated to ≥40°C, LTLD locally releases a high concentration of doxorubicin. We aimed to determine whether adding LTLD improves the efficacy of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) lesions with a maximum diameter (dmax) of 3 to 7 cm.Experimental Design: The HEAT Study was a randomized, double-blind, dummy-controlled trial of RFA ± LTLD. The 701 enrolled patients had to have ≤4 unresectable HCC lesions, at least one of which had a dmax of 3 to 7 cm. The primary endpoint was progression-free survival (PFS) and a key secondary endpoint was overall survival (OS). Post hoc subset analyses investigated whether RFA duration was associated with efficacy.Results: The primary endpoint was not met; in intention-to-treat analysis, the PFS HR of RFA + LTLD versus RFA alone was 0.96 [95% confidence interval (CI), 0.79-1.18; P = 0.71], and the OS HR ratio was 0.95 (95% CI, 0.76-1.20; P = 0.67). Among 285 patients with a solitary HCC lesion who received ≥45 minutes RFA dwell time, the OS HR was 0.63 (95% CI, 0.41-0.96; P < 0.05) in favor of combination therapy. RFA + LTLD had reversible myelosuppression similar to free doxorubicin.Conclusions: Adding LTLD to RFA was safe but did not increase PFS or OS in the overall study population. However, consistent with LTLD's heat-based mechanism of action, subgroup analysis suggested that RFA + LTLD efficacy is improved when RFA dwell time for a solitary lesion ≥45 minutes. Clin Cancer Res; 24(1); 73-83. ©2017 AACR.
    Matched MeSH terms: Liver Neoplasms/pathology*
  19. Raymond AA, Isa MR, Abdullah T, Kudva MV
    Singapore Med J, 1993 Jun;34(3):276-8.
    PMID: 8266193
    A 41-year-old Malay housewife presented with recurrent chylous ascites and progressive cachexia over 17 years. A diagnosis of lymphangioleiomyomatosis (LAM) was established by laparotomy where biopsy of the liver, peritoneum and adhesions from previous surgery showed smooth muscle proliferation in the blood vessels and lymphatics. Clinically and radiologically, there was no evidence of pulmonary involvement. She was treated with dietary fat restriction and medium-chain triglycerides. This is the first case of LAM reported in Malaysia.
    Matched MeSH terms: Liver Neoplasms/pathology*
  20. Stepien M, Fedirko V, Duarte-Salles T, Ferrari P, Freisling H, Trepo E, et al.
    Cancer Epidemiol, 2016 Feb;40:179-87.
    PMID: 26773278 DOI: 10.1016/j.canep.2016.01.002
    INTRODUCTION: Serum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of hepatobiliary cancers.

    METHODS: A nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI).

    RESULTS: In multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT)=4.23, 95%CI:2.72-6.59; OR(ALP)=3.43, 95%CI:2.31-5.10;OR(AST)=3.00, 95%CI:2.04-4.42; OR(ALT)=2.69, 95%CI:1.89-3.84; OR(Bilirubin)=2.25, 95%CI:1.58-3.20). Each liver enzyme (OR(GGT)=4.98; 95%CI:1.75-14.17; OR(AST)=3.10, 95%CI:1.04-9.30; OR(ALT)=2.86, 95%CI:1.26-6.48, OR(ALP)=2.31, 95%CI:1.10-4.86) but not bilirubin (OR(Bilirubin)=1.46,95%CI:0.85-2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR(ALP)=1.59, 95%CI:1.20-2.09).

    CONCLUSION: This study shows positive associations between circulating liver biomarkers in sera collected prior to cancer diagnoses and the risks of developing HCC or IHBC, but not GBTC.

    Matched MeSH terms: Liver Neoplasms/pathology
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