Medicine

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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty

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    Pre-treatment alphafeto protein in hepatocellular carcinoma with non-viral aetiology - a prospective study
    (BioMed Central, 2017) Siriwardana, R.C.; Thilakarathne, S.; Niriella, M.A.; Dassanayake, A.S.; Gunetilleke, M.B.; Habarakada, L.C.A.; de Silva, H.J.
    BACKGROUND: Alpha-fetoprotein (AFP) is a biomarker for hepatocellular carcinoma (HCC). The significance of pre-treatment AFP (pt-AFP) in non-viral HCC (nvHCC) is not clear. METHODS: Patients with nvHCC, referred to a Hepatobiliary Clinic from September 2011-2015 were screened. HCC was diagnosed using American Association for the Study of Liver Disease guidelines, and TNM staged. nvHCC was diagnosed when HBsAg and anti-HCVAb was negative. Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores were calculated. AFP level was evaluated against patient characteristics, tumour characteristics and survival. RESULTS: Three hundred eighty-nine patients with nvHCC [age 64(12-88) years; 344(88.4%) males] were screened. Median AFP was 25.46 ng/ml (1.16-100,000). 41.2% (n = 160) Of patients had normal AFP level. 22.9% (n = 89) had AFP over 400 ng/ml. Female gender (P < 0.05), vascular invasion (P < 0.001), tumours over 5 cm (P < 0.05), late TNM stage (P < 0.001) and non-surgical candidates had higher AFP levels. Diffuse type (P < 0.001), macro vascular invasion (P < 0.001) and late stage tumours (P < 0.001) had AFP over 400 ng/ml. Having AFP below 400 ng/ml was associated with longer survival (16 vs. 7 months, P < 0.001). CONCLUSION: Pre treatment AFP has a limited value In diagnosing nvHCC, Having a AFP value over 400 ng/ml was associated with aggressive tumour behaviour and poor prognosis.
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    Association of serum ferritin with diabetes and alcohol in patients with non-viral liver disease-related hepatocellular carcinoma
    (S. Karger, 2017) Siriwardana, R.C.; Niriella, M.A.; Dassanayake, A.S.; Ediriweera, D.; Gunetilleke, B.; Sivasundaram, T.; de Silva, H.J.
    INTRODUCTION: Non-alcoholic fatty liver disease is a leading cause for hepatocellular carcinoma (HCC) in Sri Lanka. Diabetes mellitus, alcohol abuse, and liver inflammation are known to increase the risk of HCC. The present study evaluates serum ferritin levels in a cohort of patients with non-viral HCC (nvHCC). METHODOLOGY: Consecutive patients with nvHCC presenting to the Colombo North Liver transplant Service, Ragama, from January 2012 to July 2013 were investigated. All were negative for hepatitis B and C. At registration, 5 mL of serum was separated into plain tubes, stored at -80°C and analysed for ferritin using an enzyme-linked immunosorbent assay. Correlation between the serum ferritin and patient risk factors, liver status, and tumour characteristics were analysed. RESULTS: There were 93 patients with nvHCC (median age 65 [12-82] years; 82 [88.2%] males). The median ferritin level was 246.2 μg/L, and 38 (40.86%) patients had elevated ferritin. Non-diabetics (median 363.5 mg/L, p = 0.003) and alcohol abusers (median 261.2 mg/L, p = 0.018) had higher ferritin levels. On multiple-variable analysis, being non-diabetic (p = 0.013) and alcoholic (p = 0.046) was significantly associated with high serum ferritin. No association was found with body mass index, tumour stage, size, macrovascular invasion, number of nodules, alpha-fetoprotein, bilirubin, international normalized ratio, and survival. CONCLUSION: In patients with nvHCC, serum ferritin levels are higher in non-diabetics and alcoholics.
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    Diffuse-Type Hepatoma: A grave prognostic marker
    (Karger Medical and Scientific Publishers, 2017) Siriwardana, R.C.; Liyanage, C.A.H.; Gunetilleke, B.; Niriella, M.A.; de Silva, H.J.; Dassanayake, A.S.; Jayatunga, S.P.
    BACKGROUND: Data on diffuse-type hepatocellular carcinoma (HCC) are rare. HCC in Sri Lanka is rising, and the majority is related to nonalcoholic fatty liver disease. This study was planned to compare nodular- and diffuse-type HCC in this cohort. METHODS: CT scans of 227 patients with HCC negative for infective hepatitis were analyzed and grouped as nodular and diffuse from July 2011 to July 2014. Diffuse-type cancer was defined as a tumor without convex/distinct margin, diffusely infiltrating the hepatic parenchyma. There were 45 (20%) cases. The baseline liver functions, etiology, treatment, and the outcome were compared with nodular-type cancers. Stage III diffuse cancers were matched with 2 stage III nodular cancers looking at the T stage and background liver. RESULTS: There was no difference in the age (63 vs. 62 years, p = 0.937) and gender. Diffuse cancers had a low BMI (24 vs. 22, p = 0.009), a higher alpha fetoprotein (AFP) level (p < 0.001), a higher incidence of major vascular invasion (14 vs. 80%, p < 0.001), and a history of significant alcohol consumption (39 vs. 67%, p = 0.001). The baseline liver functions were similar in diffuse and nodular cancers. A large proportion (27 vs.77%, p < 0.001) of diffuse cancers were not candidates for active treatment. Overall survival was poor in the diffuse type(4.7 vs. 25 months, p < 0.001). Diffuse-type stage III cancers had a poor survival compared to matched nodular cancers (2.5 vs. 15.8 months, p = 0.001). CONCLUSION: HCC without a background of infective hepatitis were common in our cohort. These tumors are associated with high AFP levels, major vascular invasion, and a poor prognosis.
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    Clinical predictors of poor outcomes in hepatocellular carcinoma of nonviral aetiology
    (Sri Lanka Medical Association, 2017) Siriwardana, H.D.R.C.; Niriella, M.A.; Dassanayake, A.S.; de Silva, A.P.; Gunetilleke, B.; Pathmeswaran, A.; de Silva, H.J.
    INTRODUCTION & OBJECTIVES: Clinical predictors for prognosis of NASH and alcohol related (non-viral) hepatocellular carcinoma (nvHCC) is poorly described. METHODS: Patients with nvHCC, from a tertiary referral hepatobiliary clinic were prospectively screened. Clinical evaluation, liver biochemistry, pre-treatment AFP (pt-AFP) and contrast enhanced CT abdomen were performed. HCC was diagnosed using American Association for the Study of Liver Disease guidelines, and TNM staged. nvHCC was diagnosed in HCC negative for HBsAg, anti-HCVantibody, autoimmune and metabolic screening. Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores were calculated. Cox regression analysis was used to identify the factors associated with mortality. RESULTS: A total of 472 patients with nvHCC [age-64 (12-88) years; males-417 (88.3%)] were screened [261 (61.1%) had diabetes; 212 (48.8%) were regular, 85 (19.6%) social, 137 (31.6%) nonconsumers of alcohol]. 358 (83.4%) had cirrhosis [Child A (58.3%), B (32.8%), C (8.9%); median CTP 6 (1-14), MELD 11 (5-40)]. 170 (42.2%) HCCs were TNM stage 3, with median diameter 6cm (0.9-26.5). 239 (71.6%) had no vascular or visceral invasion. Median pt-AFP was 26.6ng/ml (1.16-100,000) [pt-AFP>200ng/ml: n=90 (31.4%) pt-AFP>400ng/ml: n=68 (23.8%)]. Gender, alcohol use (consumer/not), diabetes (present/absent), cirrhosis (present/absent), Child-class (A or B/C), total diameter (<5cm or ≥5cm), nodularity (single/multiple), vascular invasion (present/absent), TNM stage (early/late) and pt-AFP level (<200 or ≥200ng/ml) were assessed as predictors of mortality. On bivariate analysis, Child B/C class (p<0.05), vascular invasion (p<0.001), TNM stage 3 and 4 (p<0.05) and pt- AFP≥200ng/ml (<0.05) were predictive of death. On multivariate analysis, TNM stage ¾ (p<0.05, HR=2.07 and 4.07 respectively) and pt-AFP level≥200ng/ml (p<0.05, HR=1.71) remained independently predictive of death. CONCLUSION: Among patients with nvHCC, TNM stage 3/4 and pt-AFP≥200ng/ml independently predicts death.
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    Significance of pre-treatment serum alpha-fetoprotein in hepatocellular carcinoma of non-viral aetiology
    (Sri Lanka Medical Association, 2016) Siriwardana, R.C.; Niriella, M.A.; Dassanayake, A.S.; de Silva, A.P.; Gunetilleke, B.; de Silva, H.J.
    INTRODUCTION: Alpha-fetoprotein (AFP) is a biomarker for hepatocellular carcinoma (HCC). The significance of pre-treatment AFP (pt-AFP) in non-viral HCC (nvHCC) is not clear. METHOD: Patients with nvHCC, referred to a Hepatobiliary Clinic from September 2011-2015 were screened. Clinical evaluation, liver biochemistry, pt-AFP and contrast enhanced CT abdomen were performed. HCC was diagnosed using American Association for the Study of Liver Disease guidelines and TNM staged. nvHCC was diagnosed in HCC, negative for HBsAg and anti-HCVAb. Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores were calculated. All values are presented as median (range). Differences between groups were tested using Pearson’s Chi-square, Mann Whitney U and Kruskal-Wallis tests. Cumulative survival and recurrence rates were calculated by the Kaplan-Meier method. Difference between survival was evaluated by the log-rank test. A p<0.05 was considered significant. RESULTS: Three hundred and eighty nine patients with nvHCC [age 64 (12-88) years; 344 (88.4%) males] were screened. Two hundred and thirty three (59.9%) had diabetes; 187 (48.1%) were regular, 79 (20.3%) social, 123 (31.6%) non-consumers of alcohol]. Three hundred and twenty nine (84.6%) had cirrhosis [Child A (57.3%), B (32.4%), C (10.3%); median CTP 6 (1-14), MELD 11(5-28)]. One hundred and seventy seven (45.5%) HCCs were TNM stage 3, with median diameter 6cm (0.9-26.5). Two hundred and thirty three (59.9%) had no vascular or visceral invasion. Median AFP was 25.46ng/ml (1.16-100,000) [AFP<10ng/ml: n=160(41.2%), AFP>400ng/ml: n=89(22.9%)]. Females (p<0.05), vascular invasion (p<0.001), diameter>5cm (p<0.05), late TNM stage (p<0.001) and non-surgical candidates had higher AFP levels. Diffuse (p<0.001), invasive (p<0.001) and late stage tumours (p<0.001) had AFP>400ng/ml. AFP<400ng/ml was associated with longer survival compared to AFP>400ng/ml (16 vs. 7 months, p<0.001). CONCLUSIONS: Although pt-AFP was not helpful for diagnosis of nvHCC, AFP>400ng/ml was associated with aggressive tumour behaviour and poor prognosis.
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    Hepatocellular carcinoma in Sri Lanka: Where do we stand?
    (Sri Lanka Medical Association, 2013) Siriwardana, R.C.; Liyanage, C.A.H.L.; Jayatunge, D.S.P.; Dassanayake, A.; Gunetileke, M.G.; Niriella, M.A.; Sirigampola, C.; Upasena, A.; de Silva, H.J.
    INTRODUCTION AND OBJECTIVES:Hepato-cellular carcinoma (HCC) is the sixth commonest cancer worldwide. We studied 105 consecutive patients with HCC in a single tertiary care centre. METHODS: North Colombo Liver Unit maintains a prospective database of HCC since September 2011. There were 105 entries by February 2013. Decision on the best form of treatment was taken at a multidisciplinary meeting. RESULTS: The median age at presentation was 63 years (range 12-79). Patients were predominantly male 93 (87%). Alcohol consumption above the safe limit was reported in 47 (45%). Hepatitis B surface antigen or C antibody was not detected in any of the patients. Background liver cirrhosis was evident in 59 (79%). Forty two (46%) patients had single nodular tumours while in 20 (21%) it was diffusely infiltrating. Portal vein invasion was seen in 22 (20 %). Median alpha-feto protein (AFP) level was 57.25 mg/ml (1.16- 94120 ng/ml; n=72). Twenty four (33%) patients had AFP level > 400u/l. Surgery was performed in 20 (19%), liver transplant in 2 (1.9%), radiofrequency ablation or alcohol ablation in 8 (7.6%), trans arterial chemo embolization (TACE) in 44 (41.9%) and sorafinib was prescribed .in four patients. Overall mean survival was 15 months. In the 'no treatment' group, mean survival was 4 months. Surgery group had a mean survival of 20 months. CONCLUSION: Hepatitis B is not a risk factor for HCC in Sri Lankans. Median survival without treatment is 4 months.
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    Diffuse and nodular type hepatocellular carcinoma - a comparative study
    (Sri lanka Medical Association, 2015) Wickramarathne, S.D.J.; Jayarathne, V.S.; Siriwardana, R.C.; Liyanage, C.A.H.; Niriella, M.A.; Dassanayake, A.S.; Gunetilleke, M.B.; de Silva, A.P.; de Silva, H.J.
    INTRODUCTION AND OBJECTIVES: Incidence of hepatocellular carcinoma (HCC) is increasing. Diffuse HCC (dHCC) is rare and data on such tumours are limited. METHOD: Ail consenting patients with HCC referred to Colombo North Liver Unit, Ragama (September 2011-February 2014) were Included. Tumours with diffuse margins on imaging were categorized as dHCC, while tumours with clear nodular morphology were categorized as nodular HCC (nHCC). Baseline parameters, treatment options and survival were compared between the two types. RESULTS: 203 HCCs were included in the study [dHCC=41(20%):87.8% males; nHCC=162(80%) 89.5% males]. The median age at presentation in the two groups was similar [dHCC 63.58(47-76) years, nHCC 62.13(12-88) years]. More patients with dHCC had a significant alcohol intake (68.9% vs. 41.7%, p=0.002). Background cirrhosis was present in 90.2% of dHCC compared to 79.1% in nHCC (p<0.05). Aspartate transaminase, Alanine transaminase, INR, total bilirubin, platelet count and MELD scores were similar in the two groups. Median alfa fetoprotein (AFP) was significantly higher in dHCC (136 vs 31ng/mL, p<0.001). Similar typical enhancement pattern on dynamic imaging was noted in the two groups (80.5% dHCC, 84.4% nHCC). dHCC had high incidence of major vascular invasion(78% vs 23.5%, p<0.001). Seventy six point nine percent of dHCC had only palliative care compared to 28.4% in nHCC was two months compared to 8 months in nHCC. CONCLUSION: 1/5 of HCCs were of the diffuse type. Patients dHCC had a significant alcohol intake. They had higher AFP, advanced disease at presentation with more vascular invasion and a worse prognosis than nHCC.
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    Low prevalence of Hepatitis B and C molecular markers in a cohort of Sri Lankan patients with hepatocellular carcinoma
    (Sri Lanka Medical Association, 2007) Dassanayake, A.S.; Manamperi, A.; Gunawardena, N.K.; Abeyewickreme, W.; de Silva, A.P.; de Silva, H.J.
    INTRODUCTION: Hepatitis B (HBV) and C (HCV) infections are leading causes of hepatocellular carcinoma (HCC). Although HCV is the predominant aetiological factor in many parts of the world, HBV remains more important in South Asia. Detection of molecular markers is the most reliable means of diagnosing infection. Molecular studies on HBV and HCV infection in HCC have not been performed in Sri Lanka. OBJECTIVES: To investigate the prevalence of HBV and HCV using molecular markers of infection in a cohort of Sri Lankan patients with HCC. DESIGN, SETTING AND METHODS: 34 consecutive patients with HCC were investigated for evidence of HBV and HCV infection. In addition to serology, serum was tested for HBV DNA and HCV RNA by PCR (sensitivity 500 copies/ml serum) and RT-PCR (sensitivity 200 copies/ml serum ) respectively. A detailed clinical work-up, screening for diabetes mellitus and iron studies were also performed. RESULTS: Of the 34 patients, 32 (94%) -were males; median age was 68 years. All had evidence of background cirrhosis. Five had evidence of past or present HBV infection, four were HBV DNA positive, one was anti-HBc positive but HBV DNA negative, and one was HCV RNA positive. In addition, 23 (67%) had a history of alcohol abuse and 18 (52%) had long standing diabetes. None had evidence of haemochromatosis. CONCLUSIONS: Prevalence of HBV and HCV infection was low in this cohort of Sri Lankan patients with HCC. This is in keeping with the low prevalence of these infections in the community.
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    Clinical characteristics and outcome of hepatocellular carcinoma in alcohol related and cryptogenic cirrhosis:a prospective study
    (Elsevier, 2015) Siriwardana, R.C.; Niriella, M.A.; Dassanayake, A.S.; Liyanage, C.; Gunetilleke, B.; Jayathunge, S.; de Silva, H.J.
    BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is becoming a leading cause of chronic liver disease. Hepatocellular carcinoma (HCC) is one of its complications. Although the pathophysiology is unclear, it is reasonable to expect that cryptogenic cirrhosis related HCC (cryptogenic HCC) behaves differently to other types of HCC. This study prospectively compared patients with cryptogenic HCC and those with HCC related to alcoholic cirrhosis. METHODS: A total of 150 consecutive patients with HCC (89 cryptogenic HCC and 61 alcohol related HCC) referred to our unit over a 23-month period were studied. Their demographic data, liver function, tumor characteristics and outcomes were compared. RESULTS: Alcohol related HCC was seen only in males. Compared with cryptogenic HCC, alcohol related HCC had significantly higher aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio (1.7 vs 1.4, P=0.002), model for end-stage liver disease score (13 vs 11, P=0.018) and Child's score (7 vs 6, P=0.037). No significant difference was seen in platelet counts, serum sodium and AST to platelet ratio index. Single nodular tumors were more common in cryptogenic HCC, while diffuse type tumors and macroscopic vascular invasion were common in alcohol related HCC. In patients who could not be offered any treatment because of advanced tumors or poor liver function, alcohol related HCC had a significantly lower median survival (5.3 months) compared with cryptogenic HCC (9.3 months, P=0.034). CONCLUSIONS: Compared with cryptogenic HCC, alcohol related HCC had worse liver function and aggressive tumor morphology at presentation, and a higher proportion was untreatable. In patients who could not be treated, median survival was lower in patients with alcohol related HCC than in those with cryptogenic HCC.
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