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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item SLHPBA Guidelines for the management of hepatocellular carcinoma in Sri Lanka - consensus statement(College of Surgeons of Sri Lanka, 2018) Siriwardana, R.C.; Pathirana, A.A.; Siriwardana, A.K.; Espat, N.J.; Anya AdiarItem 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.Item 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.Item 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.Item 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.Item Comparison of cryptogenic and hepatitis B related hepatocellular carcinoma(Sri Lanka Medical Association, 2016) Siriwardana, R.C.; Niriella, M.A.; Dassanayake, A.S.; de Silva, A.P.; Gunetilleke, B.; Chok, K.S.H.; Lo, C.M.; Chan, S.C.; Fan, S.T.; de Silva, S.T.INTRODUCTION AND OBJECTIVES: Viral hepatitis is the leading cause for hepatocellular carcinoma (HCC) globally. Cryptogenic or non-alcoholic fatty liver related HCC is increasing and is predominant in Sri Lanka (SL). Few studies have compared cryptogenic (cHCC) and hepatitis B (bHCC) HCC. Objective of the study was to compare cryptogenic and hepatitis B related hepatocellular carcinoma. METHOD: Patients with HCC were screened at two centres, in Hong Kong (HK) and SL, from 2012-2014. HCC was diagnosed on typical CT/MRI appearance. Biopsy was performed when uncertain. Those with safe alcohol intake, no hepatotoxic exposure, and not having viral, autoimmune or inherited aetiology were considered cHCC. Demography, baseline liver status, tumour characteristics and treatment were compared between groups. A p<0.05 was considered significant. RESULTS: There were 891 patients (350-SL,541-HK). All HK patients were HBsAg positive. Two HBsAg positive SL patients, and 363 with unsafe alcohol intake were excluded. There were no hepatitis C patients. cHCC=234 and bHCC=292 were compared. There was no difference in gender, presenting age, symptoms, transaminases, platelet counts, median tumour diameter, morphology and tumour stage at presentation between groups. Significantly more cHCC had diabetes [133 vs. 67], while more bHCC were cirrhotics [269 vs.175]. At presentation, serum bilirubin was significantly higher in bHCC (1.2 vs. 0.7), while INR (1.23vs1.1) and AFP (51u/lvs.26u/l) were significantly higher in cHCC. bHCC had significantly more surgical candidates [113 vs. 50], while significantly more cHCC were transarterial- chemo-embolization (TACE) candidates [74 vs. 53]. More cHCC were unsuitable for active treatment despite similar tumour stage at presentation. CONCLUSIONS: More cHCC had diabetes and occurred in non-cirrhotic livers. Compared to bHCC, fewer cHCC were candidates for surgery or active treatment at presentation.Item 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.Item 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.Item 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.