exudates and Liver-Neoplasms

Topics: Africa; China; Diagnosis, Differential; Echinococcosis, Hepatic; Fatty Liver; Hepatomegaly; Humans; Liver Cirrhosis; Liver Diseases, Parasitic; Liver Neoplasms; Malaysia; Melanoma

The spectrum of gastrointestinal (GI) and liver diseases is recognized to have a geographical variation, which may be due to environmental or genetic differences. We aimed to explore this further in a specialist clinic serving a multi-ethnic Asian urban population.. A retrospective analysis of outpatient data from this institution's electronic medical records was conducted between January and June 2019. Clinical diagnoses of GI and liver diseases and associated demographic information were collected.. Data from 3676 adult patients (median age 62 years, female 51.1%) were available for analysis. The frequency of luminal GI, liver and pancreato-biliary diseases were 34.2%, 63.2%, and 2.6%, respectively. Among luminal GI diseases, 38.6% were functional gastrointestinal disorders and 61.4% had an organic cause. A higher proportion of patients of Indian ethnicity were diagnosed with IBD compared with other ethnic groups (India 21.9%, Malay 16.5%, Chinese 12.2%, P = 0.001). Among liver diseases, the most common etiologies were HBV (44.4%) and NAFLD (39.3%). Cirrhosis and/or hepatocellular carcinoma were present in 18% of liver diseases, with NAFLD as the most frequent etiology. Among patients with NAFLD, a higher proportion of ethnic Malays and Indians were evident (Malay 53.8% vs Chinese 28.7% vs Indian 61.1%, P < 0.001). In contrast, a greater proportion of ethnic Chinese were diagnosed with HBV compared with other ethnic groups (Malay 30.9% vs Chinese 57.5% vs Indian 8.4%, P < 0.001).. The spectrum of GI and liver diseases has a peculiar epidemiology, particularly with reference to the ethnic predilection of certain diseases.

Topics: Adult; Carcinoma, Hepatocellular; Female; Humans; India; Liver Neoplasms; Malaysia; Middle Aged; Non-alcoholic Fatty Liver Disease; Retrospective Studies

Type 2 diabetes mellitus (T2DM) is increasingly known as a risk factor of hepatocellular carcinoma (HCC). In this study, we determined the risk factors associated with HCC in T2DM patients. This was a matched case-control study conducted at two hepatobiliary referral centres in a developing country. Patients' sociodemographic, clinical, and biochemical characteristics between 1 January 2012 and 30 June 2018 were extracted from the electronic medical records and analysed using multivariate logistic regression analysis. A total of 212 case-control pairs were included. Significant risk factors included Chinese and Malay ethnicities that interacted with viral hepatitis (adjusted odds ratio [AOR] = 11.77, 95% confidence interval [CI]: 1.39-99.79) and (AOR = 37.94, 95% CI: 3.92-367.61) respectively, weight loss (AOR = 5.28, 95% CI: 2.29-12.19), abdominal pain/ discomfort (AOR = 6.73, 95% CI: 3.34-13.34), alcohol (AOR = 4.08, 95% CI: 1.81-9.22), fatty liver (AOR = 3.29, 95% CI: 1.40-7.76), low platelet (AOR = 4.03, 95% CI:1.90-8.55), raised alanine transaminase (AOR = 2.11, 95% CI: 1.16-3.86). and alkaline phosphatase (ALP) levels (AOR = 2.17, 95% CI: 1.17-4.00). Statins reduced the risk of HCC by 63% (AOR = 0.37, 95% CI: 0.21-0.65). The identification of these factors aids the risk stratification for HCC among T2DM patients for early detection and decision-making in patient management in the primary care setting.

Topics: Aged; Aged, 80 and over; Carcinoma, Hepatocellular; Case-Control Studies; Clinical Decision-Making; Diabetes Mellitus, Type 2; Female; Hepatitis, Viral, Human; Humans; Liver Neoplasms; Logistic Models; Malaysia; Male; Middle Aged; Multivariate Analysis; Retrospective Studies; Risk Factors

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of hepatocellular carcinoma (HCC) was published in 2018, and covered the diagnosis, management, treatment and follow-up of early, intermediate and advanced disease. At the ESMO Asia Meeting in November 2018 it was decided by both the ESMO and the Taiwan Oncology Society (TOS) to convene a special guidelines meeting immediately after the Taiwan Joint Cancer Conference (TJCC) in May 2019 in Taipei. The aim was to adapt the ESMO 2018 guidelines to take into account both the ethnic and the geographic differences in practice associated with the treatment of HCC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with intermediate and advanced/relapsed HCC representing the oncology societies of Taiwan (TOS), China (CSCO), India (ISMPO) Japan (JSMO), Korea (KSMO), Malaysia (MOS) and Singapore (SSO). The voting was based on scientific evidence, and was independent of the current treatment practices, the drug availability and reimbursement situations in the individual participating Asian countries.

Topics: Asia; Carcinoma, Hepatocellular; China; Humans; India; Japan; Liver Neoplasms; Malaysia; Medical Oncology; Republic of Korea; Taiwan

Asian countries account for almost three quarter of hepatocellular carcinoma (HCC) reported globally and chronic hepatitis B infection is one of the main contributors. Clinical observations show that Malay patients with chronic hepatitis B and HCC tend to have a worse outcome, when compared to other two major races in Malaysia. The objectives of this study was to determine the frequency of human leukocyte antigen (HLA) class II alleles in chronic hepatitis B patients with HCC among Malays compared to the general population to identify potential associations of HLA alleles with this disease. HLA class II typing was performed in chronic hepatitis B patients with hepatocellular carcinoma (n=12) by -polymerase chain reaction, sequence specific primer (PCR-SSP) method. There were higher allelic frequencies of certain HLA-DQB1 and HLA-DRB1 alleles; HLA-DQB1*03 (07) (41.7%), and HLA-DRB1*12 (41.7% vs 28.6%) and compared to controls (41.7% vs 29.7%). However, there was no significant statistical correlation found when compared with the normal healthy general population. This study provides an insight into the HLA Class II association with chronic hepatitis B and hepatocellular carcinoma in Malays. However, findings from this study should be validated with a larger number of samples using a high resolution HLA typing.

Topics: Carcinoma, Hepatocellular; Case-Control Studies; Female; Gene Frequency; Hepatitis B, Chronic; HLA-DQ Antigens; HLA-DRB1 Chains; Humans; Liver Neoplasms; Malaysia; Male; Middle Aged; Pilot Projects

Hepatitis B virus co-infection with other strains of viral hepatitis is associated with increased risk of liver cirrhosis and hepatic decompensation.. This is a prevalence study that assessed the genetic diversity of chronic hepatitis B patients and coinfection.. Chronic hepatitis B patients enrolled in this study were tested for antibodies of other hepatitis viruses using ELISA kits. Patient clinical profiles were collected and partial genes of HBV, HCV, and HEV were amplified, sequenced, and analyzed using phylogenetic analysis. The associations between variables were determined using the chi-squared test.. Of the 82 patients recruited for this study, 53.7% were non-cirrhotic, 22.0% cirrhotic, 20.7% acute flare and 3.7% hepatocellular carcinoma. Majority (58%) of patients had a high level of ALT (≥34 U/L). Sequence analysis showed HBV (63.9%) belonged to genotype B, HEV belonged to genotype 4 while HCV belonged to genotype 3a and the genotypes were found to be significantly associated with the clinical stage of the patients (χ2=56.632; p<0.01). Similarly, Hepatitis B e antigen was also found to be significantly associated with the clinical stage of infection (χ2=51.952; p<0.01).. This study revealed that genetic diversity was found to have a significant impact on the severity of infection.

Topics: Adult; Antibodies, Viral; Carcinoma, Hepatocellular; Cross-Sectional Studies; DNA, Viral; Female; Genetic Variation; Genotype; Hepatitis B, Chronic; Hepatitis C; Hepatitis D; Hepatitis E; Humans; Liver Cirrhosis; Liver Function Tests; Liver Neoplasms; Malaysia; Male; Middle Aged; RNA, Viral; Severity of Illness Index

Hepatocellular carcinoma (HCC) is a common cancer that is frequently diagnosed at an advanced stage. Transarterial chemoembolisation (TACE) is an effective palliative treatment for patients who are not eligible for curative treatment. The two main methods for performing TACE are conventional (c-TACE) or with drug eluting beads (DEB-TACE). We sought to compare survival rates and tumour response between patients undergoing c-TACE and DEB-TACE at our centre.. A retrospective cohort study of patients undergoing either treatment was carried out from January 2009 to December 2014. Tumour response to the procedures was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Kaplan-Meier analysis was used to assess and compare the overall survival in the two groups.. A total of 79 patients were analysed (34 had c-TACE, 45 had DEB-TACE) with a median follow-up of 11.8 months. A total of 20 patients in the c-TACE group (80%) and 12 patients in the DEB-TACE group (44%) died during the follow up period. The median survival durations in the c-TACE and DEB-TACE groups were 4.9 ± 3.2 months and 8.3 ± 2.0 months respectively (p=0.008). There was no statistically significant difference noted among the two groups with respect to mRECIST criteria.. DEB-TACE demonstrated a significant improvement in overall survival rates for patients with unresectable HCC when compared to c-TACE. It is a safe and promising approach and should potentially be considered as a standard of care in the management of unresectable HCC.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Doxorubicin; Female; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Malaysia; Male; Middle Aged; Response Evaluation Criteria in Solid Tumors; Retrospective Studies; Survival Rate; Tertiary Care Centers; Treatment Outcome; Young Adult

Hepatocellular carcinoma (HCC) is an important cancer in Malaysia. This study aimed to determine the epidemiological characteristics and clinical presentations of patients in a multiracial population consisting of three major Asian races: Malays, Chinese and Indians.. Consecutive patients with HCC were prospectively studied from 2006 to 2009. HCC was diagnosed principally on multiphasic computed tomography and magnetic resonance imaging scans of the liver. The tumor was staged according to the Barcelona Clinic Liver Cancer (BCLC) classification.. Altogether, 348 patients were diagnosed with HCC. There were 239 (68.7%) Chinese patients, 71 (20.4%) Malays and 38 (10.9%) Indians, with the median age of 62.5 years and the male to female ratio of 3.4:1. The predominant etiology in Malay and Chinese patients was hepatitis B virus infection (>60%) and in Indian patients was alcohol intake (26.3%) and cryptogenic cause (29.0%). Hepatitis C was seen in 18.3% of Malays, but less than 10% in Chinese and Indians. BCLC staging was: Stage A, 120 (34.5%); Stage B, 75 (21.6%); Stage C, 84 (24.1%); and Stage D, 69 (19.8%). A larger proportion of Indian than Chinese and Malays patients (44.7%) presented with stage D disease. Portal vein invasion was noted in 124 patients (35.6%) and extrahepatic metastases in 68 (19.5%). Surgical resection and radiofrequency ablation with curative intent was carried out in >90% of stage A patients and transarterial chemoembolization in 49.3% and 21.4% of stages B and C patients, respectively.. HCC is most common among Chinese, followed by Malays and Indians in Malaysia. The etiology of HCC shows a peculiar racial pattern.

Topics: Aged; alpha-Fetoproteins; Biomarkers, Tumor; Carcinoma, Hepatocellular; China; Female; Health Surveys; Humans; India; Liver Cirrhosis; Liver Neoplasms; Lung Neoplasms; Magnetic Resonance Imaging; Malaysia; Male; Middle Aged; Neoplasm Staging; Population Surveillance; Tomography, X-Ray Computed

Up to 25% of chronic hepatitis B (CHB) patients eventually develop hepatocellular carcinoma (HCC), a disease with poor prognosis unless detected early. This study identifies a blood-based RNA biomarker panel for early HCC detection in CHB.. A genome-wide RNA expression study was performed using RNA extracted from blood samples from Malaysian patients (matched HCC, CHB, controls). Genes differentiating HCC from controls were selected for further testing using quantitative real-time polymerase chain reaction. Finally, a 6-gene biomarker panel was identified and characterized using a training set (cohort I = 126), and tested against 2 test sets (cohort II = 222; cohort III = 174). The total number of samples used for each group is: HCC + CHB = 143, CHB = 211, control = 168.. Our gene panel displays a consistent trend distinguishing HCC from controls in our test sets, with an area under receiver-operating characteristic curve of 0.9 in cohort III. Our independent test set (cohort III) showed that the gene panel had a sensitivity of 70% with a specificity of 92%. The biomarker profile for HCC was consistently detected in a small subgroup of CHB patients, thus potentially predicting early, preclinical cases of cancer that should be screened more intensively.. The biomarkers identified in this study can be used as the basis of a blood-based test for the detection of early HCC in CHB.

Topics: Adult; Area Under Curve; Biomarkers, Tumor; Carcinoma, Hepatocellular; Case-Control Studies; Databases, Genetic; Early Detection of Cancer; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Genetic Testing; Genome-Wide Association Study; Hepatitis B, Chronic; Humans; Liver Neoplasms; Malaysia; Male; Middle Aged; Oligonucleotide Array Sequence Analysis; Predictive Value of Tests; Real-Time Polymerase Chain Reaction; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; ROC Curve

The risk of febrile neutropaenia (FN) and treatment related death (TRD) with first line palliative chemotherapy for de novo metastatic breast cancer (MBC) remains unknown outside of a clinical trial setting despite its widespread usage. This study aimed to determine rates in a large cohort of patients treated in the University of Malaya Medical Centre (UMMC).. Patients who were treated with first line palliative chemotherapy for de novo MBC from 2002-2011 in UMMC were identified from the UMMC Breast Cancer Registry. Information collected included patient demographics, histopathological features, treatment received, including the different chemotherapy regimens, and presence of FN and TRD. FN was defined as an oral temperature >38.5° or two consecutive readings of >38.0° for 2 hours and an absolute neutrophil count <0.5x109/L, or expected to fall below 0.5x109/L (de Naurois et al, 2010). TRD was defined as death occurring during or within 30 days of the last chemotherapy treatment, as a consequence of the chemotherapy treatment. Statistical analysis was performed using the SPSS version 18.0 software. Survival probabilities were estimated using the Kaplan-Meier method and differences in survival compared using log-rank test.. Between 1st January 2002 and 31st December 2011, 424 patients with MBC were treated in UMMC. A total of 186 out of 221 patients with de novo MBC who received first line palliative chemotherapy were analyzed. The mean age of patients in this study was 49.5 years (range 24 to 74 years). Biologically, ER status was negative in 54.4% of patients and Her-2 status was positive in 31.1%. A 5-flourouracil, epirubicin and cyclophosphamide (FEC) chemotherapy regimen was chosen for 86.6% of the cases. Most patients had multiple metastatic sites (58.6%). The main result of this study showed a FN rate of 5.9% and TRD rate of 3.2%. The median survival (MS) for the entire cohort was 19 months. For those with multiple metastatic sites, liver only, lung only, bone only and brain only metastatic sites, the MS was 18, 24, 19, 24 and 8 months respectively (p-value= 0.319).. In conclusion, we surmise that FEC is a safe regimen with acceptable FN and TRD rates for de novo MBC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Brain Neoplasms; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Chemotherapy-Induced Febrile Neutropenia; Cohort Studies; Female; Humans; Liver Neoplasms; Lung Neoplasms; Malaysia; Middle Aged; Mortality; Palliative Care; Retrospective Studies; Young Adult

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.

Topics: Adult; Carcinoma, Hepatocellular; Female; Follow-Up Studies; Humans; Liver Neoplasms; Malaysia; Male; Middle Aged; Neoplasm Staging; Prognosis; Retrospective Studies; Survival Rate

The incidence of hepatocellular carcinoma (HCC) in Malaysia for the year 2001 was 2.8 per 100,000 people. The mortality rate is increasing. A retrospective cohort study measuring the survival of HCC patients who received treatment in Selayang Hospital was conducted from 1 January 2003 to 31 December 2006. The main objectives of the study were to measure the survival of the patients and to understand the influencing factors, especially ethnicity. The subjects were newly diagnosed cases of HCC by CT scan and histopathological assessment who underwent futher investigations and treatments in Hospital Selayang (inception cohort). The survival time was measured from the date of diagnosis until the subjects died, or failed to follow-up at the end of the study period (31 December 2007). A total of 299 patients were selected with 95 patients dying, the majority among Chinese (39.1%). Subgroup analysis according to ethnicity proved significantly that Chinese patients who had smaller tumor, less number of nodules, low AFP level, Child Pugh Class A and received surgical treatment had a better median survival rate compared to other ethnic groups. Malay (cHR: 1.3, 95%CI; 0.89-1.85) and Indian (cHR: 1.3, 95%CI; 0.74-2.26) patients had a poor survival compared to Chinese patients, but not in the final model. Therefore ethnicity may play a role in survival of HCC patients, but not as a main hazard prognostic factor.

Topics: Carcinoma, Hepatocellular; Cohort Studies; Humans; Liver Neoplasms; Malaysia; Retrospective Studies

Exposure to aflatoxins in the adult Malaysian diet was estimated by analysing aflatoxins in 236 food composites prepared as "ready for consumption". Dietary exposure to aflatoxin B1 (AFB1) ranged from 24.3 to 34.00 ng/kg b.w./day (lower to upper bound), with peanuts being the main contributor. Estimated liver cancer risk from this exposure was 0.61-0.85 cancers/100,000 population/year, contributing 12.4%-17.3% of the liver cancer cases. Excluding AFB1 occurrence data higher than 15 µg/kg reduced exposure by 65%-91% to 2.27-11.99 ng/kg b.w./day, reducing the cancer risk to 0.06-0.30 cancers/100,000 population/year (contributing 1.2%-6.1% liver cancer cases). Reducing further the ML of AFB1 from 15 to 5 µg/kg yielded 3%-7% greater drop in the exposure to 0.47-10.26 ng/kg b.w./day with an estimated risk of 0.01-0.26 cancers/100,000 population/year (0.2%-5.1% liver cancer cases attributed to dietary AFB1). These findings indicate that current MLs are adequate in protecting Malaysians' health.

Topics: Adult; Aflatoxin B1; Arachis; Diet; Environmental Exposure; Food Contamination; Fungi; Humans; Liver Neoplasms; Malaysia; Nuts; Risk Assessment; Risk Factors

To determine the etiology of liver cirrhosis and risk factors for hepatocellular carcinoma (HCC) in a multiracial Asian population.. Consecutive patients with liver cirrhosis presenting to outpatient clinics and inpatient service at the University of Malaya Medical Centre from 1 April 2006 to 31 May 2009 were included.. A total of 460 patients were included in the study: 317 male patients (68.9%) and 143 female patients (31.1%), with a mean age of 58.8years (range: 15-87years). The major causes of cirrhosis were: chronic hepatitis B, n=212, 46.1%; chronic hepatitis C, n=85, 18.5%; cryptogenic, n=71, 15.4%; alcohol, n=58, 12.6% and autoimmune, n=9, 2.0%. Alcohol was the main etiology in Indians (51.1%) compared to Malay (0%) and Chinese (4.4%) (both P<0.001). Hepatitis B was the predominant etiology in Malay (47.9%) and Chinese (58.8%) compared to Indians (5.6%) (both P<0.001). Hepatitis C cirrhosis was highest in Malays (25.0%). 136 patients (29.6%) had concurrent HCC. Male sex (P<0.001), age>60years (P=0.014), hepatitis B (P<0.001), hepatitis C (P=0.006) and cryptogenic cause (P=0.002) were found to be independent risk factors for HCC.. The etiology of cirrhosis has a peculiar pattern based on racial differences in alcohol intake and in the prevalence of hepatitis B.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alcohol Drinking; Asian People; Carcinoma, Hepatocellular; Chi-Square Distribution; China; Cross-Sectional Studies; Female; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; India; Liver Cirrhosis; Liver Neoplasms; Malaysia; Male; Middle Aged; Odds Ratio; Prevalence; Risk Assessment; Risk Factors; Young Adult

Transforming growth factor beta-1 (TGF-beta-1) is a multifunctional cytokine involved in the regulation of growth and differentiation of both normal and transformed cells. The main aim of this study was to determine whether TGF-beta-1 or alpha fetoprotein (AFP) or the combination of the two is a better indicator for hepatocellularcarcinoma (HCC). Serum TGF-beta-1 and AFP were measured by ELISA in 40 healthy subjects, 23 patients with hepatocellular carcinoma (HCC), 70 patients with hepatitis B, 26 patients with hepatitis C and 16 patients with liver cirrhosis (LC). Patients with liver diseases showed significantly higher serum TGF-beta-1 values (> 3 fold) compared to control subjects. As for serum AFP, significant elevation was only observed for HCC cases. Serum TGF-beta-1 exhibited higher percent sensitivity compared to serum AFP in all liver diseases. Combination of serum TGF-beta-1 and AFP increased specificities in all cases studied. In conclusion, serum TGF-beta-1 is a more sensitive marker for HCC when compared to serum AFP and its specificity is increased when combined with serum AFP.

Topics: Adolescent; Adult; Aged; alpha-Fetoproteins; Biomarkers, Tumor; Carcinoma, Hepatocellular; Case-Control Studies; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Humans; Liver Diseases; Liver Neoplasms; Malaysia; Middle Aged; Sensitivity and Specificity; Transforming Growth Factor beta1

Previous studies showed that the frequency of beta-catenin mutation was different in mice when induced by different chemicals. The aim of this study is to compare the expression of beta-catenin and p53 in hepatocellular carcinoma (HCC) from areas with exposure to high and low levels of aflatoxin B1 (AFB1).. Thirty-five and twenty HCC samples from Guangxi and Malaysia, respectively, were studied. The expression of beta-catenin and p53 was determined by immunohistochemistry.. The overexpression of beta-catenin was detected in 65.7% of HCC tissues and 37.1% in adjacent liver tissues samples from Guangxi, China. Similarly, overexpression of beta-catenin was also detected in 60.0% of HCC tissues and in 35.0% of adjacent liver tissues samples from Malaysia. The overexpression of p53 was detected in 42.9% of HCC specimens from Guangxi and in 25.0% of HCC specimens from Malaysia. There was a relationship between the expression of beta-catenin and hepatitis B virus (HBV) infection in the adjacent liver tissues in Guangxi, and between the expression of beta-catenin and p53 in HCC tissues in Malaysia.. The differences in the exposure to AFB1 did not affect the overexpression of beta-catenin in the development of HBV-associated HCC.

Topics: Adult; Aflatoxin B1; Aged; beta Catenin; Carcinoma, Hepatocellular; China; Cytoskeletal Proteins; Environmental Exposure; Female; Hepatitis B; Humans; Immunohistochemistry; Liver Neoplasms; Malaysia; Male; Middle Aged; Mutation; Sequence Analysis, DNA; Trans-Activators; Tumor Suppressor Protein p53

The aim of this study is to investigate the potential correlation between the expression of phosphorylated glycogen synthase kinase-3beta (phospho-GSK-3beta) and beta-catenin, and the mutations of beta-catenin gene at the consensus GSK-3beta phosphorylation site. The reason for this approach is to gain a better understanding of the molecular mechanisms of hepatocarcinogenesis in Malaysia. The expression of phospho-GSK-3beta and beta-catenin by immunohistochemistry and the mutations of beta-catenin were studied in 23 hepatocellular carcinoma (HCC) and surrounding tissues. Overexpression of phospho-GSK-3beta and beta-catenin was found in 12/23 (52.2%) and 13/23 (56.5%) in HCC tissues, 6/23 (26.1%) and 9/23 (39.1%) in surrounding tissues, respectively. Overexpression of beta-catenin in HCC tissues compared to the surrounding liver tissue was found to be higher in HCC tissues (p=0.015). In addition, we found that the expression of phospho-GSK-3beta was related with the accumulation of beta-catenin in surrounding tissues (p<0.05). The expression of phospho-GSK-3beta and its association with the development of HCC is reported for the first time. In addition, this is the first report from Malaysia which shows that there are no mutations at the GSK-3beta consensus phosphorylation sites on beta-catenin gene in all 23 paired HCC and surrounding tissues. This result differed from HCC in geographical areas with high aflatoxin exposure.

Topics: Adult; Aged; beta Catenin; Carcinoma, Hepatocellular; Cell Membrane; Cytoskeletal Proteins; Female; Gene Expression Regulation, Neoplastic; Glycogen Synthase Kinase 3; Humans; Immunoenzyme Techniques; Liver; Liver Neoplasms; Malaysia; Male; Middle Aged; Mutation; Phosphorylation; Trans-Activators

A study was conducted at the Department of Pathology, University of Malaya Medical Centre, Kuala Lumpur into the histological type (WHO classification), grade (modified Edmondson and Steiner's grading system), mitotic rate, bile production, hyaline globule and Mallory hyaline formation of 52 cases of hepatocellular carcinoma (HCC) diagnosed during a 13-year period between 1st January 1990 to 31st December 2002. In addition, associated cirrhosis, dysplasia (large liver cell dysplasia: LLCD and small liver cell dysplasia: SLCD) and microvascular permeation were also looked for whenever the situation permitted. The patients' ages ranged from 21-years to 85-years (mean = 58.7 years) with a predilection for males and Chinese. Histologically, majority (73.1%) of the tumours demonstrated a trabecular pattern of growth. The bulk (73%) of the tumours were either of grade II or III differentiation. Mitotic activity ranged between 0-100/10 high power fields (hpf) with a mean of 22.2/10 hpf. Bile was noted in 25%, hyaline globules 17.3% and Mallory bodies in one case. Concomitant cirrhosis was present in 73.5%. 73.5% of the cases had associated LLCD. 5 with LLCD also showed SLCD. Microvascular permeation was shown in 76.2% of cases. On comparison with findings from other studies, no major difference seems to exist between the histological characteristics of our HCC cases and that of other populations.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Hepatocellular; Female; Humans; Liver Neoplasms; Malaysia; Male; Middle Aged

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.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; alpha-Fetoproteins; Antigens, Tumor-Associated, Carbohydrate; beta 2-Microglobulin; Biomarkers, Tumor; CA-125 Antigen; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Child; Female; Ferritins; Humans; Liver Neoplasms; Malaysia; Male; Middle Aged; Reproducibility of Results; ROC Curve; Sensitivity and Specificity

Hepatocellular carcinoma (HCC) is one of the commonest cancers in Asian males. In Malaysia, it is one of the ten most common cancers amongst the male population. Most of our patients with HCC present to us rather late and almost all die within 4 months of diagnosis. HCC occurs more commonly in patients with cirrhosis associated with hepatitis B and C infections. Screening for HCC can lead to early detection of small tumours (< 5 cm) that are more amenable to surgical resection, resulting in improved survival rates. The average 5-year survival rate for those who have undergone surgical resection is 68% (range, 22-73%). Better results are obtained with the smaller tumours (< 2 cm in diameter). Patients with chronic hepatitis B and C infection especially those who are > 45 years of age, who have concomitant cirrhosis or have a family history of HCC should be examined every 3-6 months with periodic serum alpha-fetoprotein (AFP) measurements and abdominal ultrasound examinations. Abdominal ultrasound is useful in the detection of small tumours. While mass screening for HCC is not cost-effective in countries of low incidence of HCC, screening of high risk groups may be justified in countries with a high endemicity of HBV infection. Screening for HCC in Japan, Taiwan and China appears to yield better results than those in the West. Nonetheless, primary prevention with mass hepatitis B vaccination and blood donor screening for anti-HCV is expected to make a much greater impact in the control of HCC in the years to come.

Topics: Carcinoma, Hepatocellular; Cost-Benefit Analysis; Humans; Liver Neoplasms; Malaysia; Mass Screening

Chronic hepatitis B virus (HBV) infection constitutes a major public health problem particularly in developing countries in East Asia, South-East Asia, the Pacific Basin and Africa. In Malaysia, a developing nation in the South East Asian region, the chronic HBV carrier rate varies between < 1% to about 10% depending on the ethnic group studied. The highest frequency is seen among the Chinese, followed by the Malays and lastly the Indians, with a male preponderance of between 2 : 1 and 3 : 1. Exposure to the virus among the adult population is estimated to be about 15%, 26% and 36% among the Indians, Malays and Chinese respectively. Serological study of adult chronic HBV carriers showed a frequency of HBe antigenemia of about 35%, with a significant decreasing trend with age. HBV DNA status generally correlated with the HBe status. An atypical profile of anti-HBe associated with serum HBV DNA is found in some carriers; in most instances, this is related to seroconversion from HBe antigenemia to anti-HBe. Chronic complications of HBV infection include the development of hepatocellular carcinoma (HCC), the occurrence of which closely parallel that of HBsAg carrier rate. In Malaysia, HCC is the third most common malignant neoplasm and among the 10 leading causes of death. About 80% of our HCC cases are HBV associated. All 3 ethnic groups are afflicted, the highest frequency being among the Chinese. Males show a disproportionate risk with an odds ratio of 3.93 (p < 0.0001).

Topics: Asian People; Carcinoma, Hepatocellular; Carrier State; China; Ethnicity; Female; Hepatitis B virus; Hepatitis B, Chronic; Humans; India; Liver Neoplasms; Malaysia; Male

We studied the presence of Hepatitis C Virus (HCV) antibodies in a defined Malaysian population and examined the association, if any, between HCV and the Hepatitis B Virus (HBV), using sensitive recombinant DNA second generation Enzyme Immunoassay (EIA) test kits. This sero-prevalence study comprised 1,434 sera from eleven distinct groups comprising intravenous drug users (IVDU), haemophiliacs, male homosexuals, female prostitutes, healthy blood donors, staff of dialysis unit and laboratory personnel, chronic renal failure patients undergoing dialysis (CRFD), patients with liver cirrhosis, chronic active hepatitis, chronic persistent hepatitis and primary liver cancer. Except in laboratory personnel and dialysis staff, HCV antibodies were detected in each group of patients ranging from 3% in blood donors to 85% in IVDU. The main modes of HCV transmission identified were parenteral drug use, transfusion and/or dialysis related. The HBV was found to be the major viral etiological agent in 75% of chronic liver disease (CLD); while in 10% of cases both HCV and HBV were detected. HCV was implicated as the sole viral agent in only a small proportion (1.5%) of patients with chronic liver disease.

Topics: Carcinoma, Hepatocellular; Female; Hemophilia A; Hepacivirus; Hepatitis; Hepatitis Antibodies; Hepatitis B Antibodies; Hepatitis B Surface Antigens; Hepatitis C; Hepatitis, Chronic; Homosexuality; Humans; Liver Cirrhosis; Liver Neoplasms; Malaysia; Male; Sex Work; Substance Abuse, Intravenous

Based on data collected by the population-based Singapore Cancer Registry over the period 1968 to 1982, baseline epidemiological characteristics and incidence trends of primary liver cancer were described. This will facilitate the interpretation of future trends, especially in the light of new interventions such as hepatitis B immunisation. The primary liver cancer incidence is four times higher in males than in females, with the incidence peaked in the seventh decade. The incidence rate was higher in the Chinese than in Malays and Indians and marginally higher among foreign born than Singapore born Chinese. A general declining trend in liver cancer incidence was especially notable in the local born Chinese. Misclassification of metastatic carcinomas in the earlier years of cancer registration may have contributed to the initial higher incidence. Definitive decrease in incidence as a result of hepatitis immunisation will only be seen in another two to three decades.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Hepatocellular; China; Cohort Studies; Female; Humans; India; Liver Neoplasms; Malaysia; Male; Middle Aged; Retrospective Studies; Singapore

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.

Topics: Adult; Carcinoma, Hepatocellular; China; Ethnicity; Female; Hepatitis B; Humans; Liver; Liver Cirrhosis; Liver Neoplasms; Malaysia; Male; Middle Aged; Sex Factors

Twenty Malaysian patients with unresectable primary liver cell cancer were prospectively studied at the General Hospital, Kuala Lampur, and were compared for clinical features with an equal number each of African and American patients being studied by the Eastern Cooperative Oncology Group. The patients received intravenous 5-FU and oral MeCCNU which was used for the first time in an Asian country. Most of the Malaysian patients were Chinese, belonged to younger age groups, and presented with massive hepatomegaly, jaundice, and fever. Toxicity to MeCCNU invariably occurred in the form of leukopenia or thrombocytopenia, but none life threatening. Partial response was seen in 20% of Malaysians as compared to 16% in Americans and none in Africans. Malaysians achieved a median survival of 16 weeks compared to 28 weeks in Americans and only eight weeks in Africans. Malaysian Chinese patients were all HBc Ab + ve. Other factors which may have played an etiologic role in the induction of primary liver cancer included alcohol, Chinese herbal medicines, aflatoxin and habitual use of medicated rubbing oils.

Topics: Adult; Aged; Carcinoma, Hepatocellular; Female; Fluorouracil; Follow-Up Studies; Humans; Liver Neoplasms; Malaysia; Male; Middle Aged; Nitrosourea Compounds; Semustine; South Africa; United States

Two hundred eight-eight hepatic resections performed over the past 15 years are discussed. The safety and success achieved are attributed to the original work in Malaysia on the anatomy of the liver and its anomalies, the use of surgical instruments specially designed for hepatic resection, various types of resections devised and studies on aids to liver regeneration after resection. The diversity of the principles and practice of surgery in the Western countries compared with those in Malaysia is illustrated.

Topics: Calculi; Carcinoma, Hepatocellular; Cysts; Humans; Liver; Liver Abscess; Liver Diseases; Liver Neoplasms; Liver Regeneration; Malaysia; Surgical Instruments

An abnormal, fast-moving 5'-nucleotide phosphodiesterase isozyme was found in 90.0% of 20 Malaysian patients with primary hepatoma and in 23.5% of 391 Malaysian patients with various malignant diseases; it was also discovered in 42.9% of 14 Malaysian and American patients with clinically active hepatitis B infection; in 16.7% of 18 healthy American blood bank donors who were positive for hepatitis B surface antigen (HBsAg); in 13.9% of 287 healthy Malaysian blood bank donors, some positive for HBsAg; and in none of 160 healthy American donors who were negative for HBsAg. A correlation of this abnormal isozyme with hepatoma and with infectious hepatitis B is clearly evident.

Topics: Adult; Carcinoma, Hepatocellular; Female; Hepatitis B; Humans; Isoenzymes; Liver Neoplasms; Malaysia; Male; Neoplasms; Nucleotides; Phosphodiesterase I; Phosphoric Diester Hydrolases; United States

Topics: Adenoma, Bile Duct; Carcinoma, Hepatocellular; Child; Child, Preschool; Female; Humans; Infant; Liver Neoplasms; Malaysia; Male

We present a study of 288 hepatic resections carried out in Malaysia for the past fifteen years. First, we describe our indications for hepatic resectins which are not limited to hepatic trauma and hepatomas, but also include hepatic abscesses, cysts, intrahepatic calculi and hemangiomas. Second, we give a simplified classification of hepatic resections using accurate terminology. Third, we describe the safety of hepatic resections in our hands which we believe is due to specially designed surgical instruments and the accurate decision making process at surgery. We have had minimum postoperative mortality and no intraoperative deaths so far. Finally, while analysing each indication we have drawn vignettes from our experience for the past fifteen years.

Topics: Calculi; Carcinoma, Hepatocellular; Cysts; Hemangioma; Hepatectomy; Humans; Liver; Liver Abscess; Liver Diseases; Liver Neoplasms; Malaysia

Topics: Adolescent; Adult; Aged; Breast Neoplasms; Child; Child, Preschool; Female; Hospitals, University; Humans; Infant; Leukemia; Liver Neoplasms; Lung Neoplasms; Malaysia; Male; Middle Aged; Neoplasms; Stomach Neoplasms; Uterine Cervical Neoplasms

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.

Topics: Carcinoma, Hepatocellular; Female; Hepatitis B Antigens; Humans; Liver Cirrhosis; Liver Neoplasms; Lymphocytes; Malaysia; Male

The level of serum alpha-fetoprotein (AFP) was estimated by radioimmunoassay in 153 normal healthy Malysians of different ethnic groups. The mean level was 7.5 In1/ml (SD 2.28InU/ml). Among 330 patients with malignant tumors, 11 had increased levels of AFP. The only patient who had hepatoma had a very high level of serum AFP. High levels were also found in three of four patients with dysgerminoma of the ovary, in the only two patients with carcinoma of the testis, and in one patient with secondary carcinoma of the humerus of unknown origin. Lower, but significantly increased levels were observed in one patient (of 48) with breast carcinoma, one patient (of 8) with basal cell carcinoma of the nose, one patient (0f 27) with carcinoma of the lung, and one patient (of 59) with nasopharynegeal carcinoma.

Topics: Adult; alpha-Fetoproteins; Breast Neoplasms; Carcinoma, Hepatocellular; Female; Fetal Proteins; Humans; Liver Diseases; Liver Neoplasms; Malaysia; Male; Neoplasms; Nose Neoplasms; Ovarian Neoplasms; Pregnancy; Racial Groups; Testicular Neoplasms

Necropsies were performed on 285 consecutively unclaimed Orang Asli bodies from Gombak Orang Asli Hospital during an eight-year period from May 1967 to April 1975. Of the 25 malignant neoplasms, hepatocellular carcinoma was by far the commonest (36%). The nine patients with this neoplasm had coexistant macronodular cirrhosis. There were 20 cases of cirrhosis; 45% of these had coexistant hepatocellular carcinoma. The 53,000 Orang Aslis living in West Malaysia comprise three tribes, the Negrito, Senoi, and Melayu Asli (Proto Malays). The Sinoi appear to have a high predilection for liver cancer, all our nine cases occurring in this group. These aboriginal people live in the jungles where they practice shifting cultivation and maintain their own dietary and social customs. Detailed studies of their dietary habits may provide a clue to the etiology of liver cancer in these people.

Topics: Adult; Carcinoma, Hepatocellular; Female; Humans; Liver Cirrhosis; Liver Neoplasms; Malaysia; Male; Middle Aged

A review of 352 patients with primary liver cell carcinoma treated by the author is presented. The poor rate of resectability (7 per cent) has necessitated various forms of treatment over the years. These are described in detail. Based on this experience, the current form of treatment for nonresectable carcinoma is summarized. Although it is too early to assess this form of treatment, initial results appear to be promising. A second report in the near future is planned.

Topics: Age Factors; Alcoholism; alpha-Fetoproteins; Blood Donors; Carcinoma, Hepatocellular; Developing Countries; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Hepatectomy; Hepatic Artery; Hepatitis B Antigens; Humans; Liver Cirrhosis; Liver Neoplasms; Malaysia; Male; Mycotoxins; Nutrition Disorders; Prognosis; Racial Groups

Alpha-Fetoprotein (AFP) levels of 1,335 males (15 years and older) of seven ethnic groups (Chinese, Indians, and Malays from Singapore, Caucasians from Lyon, and Blacks from Nairobi, forest, and the savanna region of the Ivory Coast) were determined by radioimmunoassay. A few elevated levels (up to 30 nanounits/ml) were detected in some normal individuals, especially in the older age-groups. In addition, there was a systematic age-dependency of AFP levels particularly evident in the groups from Singapore-Lyon, in which there was a 50% AFP increase between the ages of 20 and 40. Comparison between Africans on the one hand and people from Singapore-Lyon on the other hand revealed highly significant differences (p less than 0.001), especially in the younger groups, whereas Chinese, Malays, and Indians from Singapore had very similar AFP pattern; this suggests an important role for environmental factors in the regulation of AFP levels. The age dependency of the presumed effect of environmental factors is in keeping with experimental data showing that young animals respond more vigorously to AFP-stimulating factors. Although the incidence of hepatocellular carcinoma (HCC) differs in the three Singapore groups (the highest in Chinese and the lowest in Indians), no relationship was observed in this study between mean AFP level and HCC incidence in Singapore.. The levels of alpha fetoproteins (AFP) were quantitated in 7 ethnic groups (Chinese, Indians, and Malays from Singapore, Caucasians from Lyon, and Blacks from the Nairobi, forest, and savanna region of the Ivory Coast) by radioimmunoassay. Sera from 1335 men (aged 15 years or older) were assayed. Mean AFP levels increased with age and varied among populations. A few elevated (30 nU/ml) AFP values were detected in normal individuals, mostly from older age groups. The systematic age-dependency was particularly evident in groups from Singapore-Lyon, in which there was a 50% increase in AFP between age 20 and 40 years. When Africans were compared on the one hand and people from Singapore-Lyon were compared on the other, highly significant differences were revealed in AFP patterns (P .001). This was true especially in the younger groups; whereas Chinese, Malays, and Indians from Singapore had very similar AFP patterns, suggesting an important role for environmental factors in regulation of AFP levels. The age dependency observed paralleled experimental data where laboratory animals responded most vigrously to AFP-stimulating factors the younger they were. Although the hepatocellular carcinoma incidence differs in the 3 Singapore groups (Chinese highest and Indians lowest), no relationship was observed bwtween mean AFP level and hepatocellular carcinoma incidence in Singapore.

Topics: Adult; Age Factors; Aged; alpha-Fetoproteins; Asian People; Black People; China; Cote d'Ivoire; Dose-Response Relationship, Drug; Epitopes; Fetal Proteins; France; Hepatitis B Antigens; Humans; India; Kenya; Liver Neoplasms; Malaysia; Male; Middle Aged; Precipitin Tests; Racial Groups; Singapore; White People

Topics: Burkitt Lymphoma; Female; Humans; Liver Neoplasms; Lung Neoplasms; Malaysia; Male; Neoplasms; Racial Groups; Sex Factors

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Liver Diseases; Liver Neoplasms; Malaysia; Male; Middle Aged; Radionuclide Imaging

Topics: Carcinoma; Humans; Liver Neoplasms; Malaysia