Medicine
Permanent URI for this communityhttp://repository.kln.ac.lk/handle/123456789/12
This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
Browse
6 results
Search Results
Item Demographics, pathological characteristics and survival in urothelial bladder cancer in a cohort of Sri Lankan patients.(The Sri Lanka Medical Association, 2022) Malalasekera, A.P.; Ediriweera, D.; Goonewardena, S.A.S.; Perera, N.D.; Abeygunasekara, A.; Jayasekara, R.W.; Wettasinghe, K.; Dissanayake, V.H.W.; Lokuhetty, M.D.S.INTRODUCTION: Bladder cancer has the 9th highest incidence among Sri Lankan males. This study describes the demographic profiles and survival in bladder cancer patients at two tertiary care centres in Sri Lanka. METHODS: A group of patients with urothelial bladder cancer, presenting for the first time for definitive treatment, were prospectively enrolled from 2013 to 2017. RESULTS: There were sixty-six patients, with median age of 65 years and male to female ratio of 7:1. Histopathologically pTa 24%, pT1 47% and pT2 29%. Of the pT1 tumours 61% were low grade (LG). The majority (71%) of non-muscle invasive bladder cancer (NMIBC) patients underwent transurethral resection of bladder tumour only. For the entire cohort the 5-year overall survival was 59% and cancer specific survival (CSS) was 65%. CSS in NMIBC was 75% and 30% in muscle invasive bladder cancer (MIBC). The 5-year female CSS (22%) was significantly lower than in males (71%). CONCLUSION: Our cohort has a high male to female ratio. The percentage of MIBC was lower than reported in previous Sri Lankan studies. Of the pT1 tumours there is a higher percentage of pT1 LG patients in comparison to Western reports. There is low utilisation of intravesical mitomycin / bacillus Calmette–Guérin (BCG) in the treatment of NMIBC. The 5-year CSS in the Sri Lankan (lower middle-income economy) cohort lies between the values of high-income economies and upper middle-income economies in Asia. The reasons for poor CSS among Sri Lankan women with bladder cancer needs to be further investigated.Item The new normal of medical education - challenges and opportunities(South East Asia Regional Association for Medical Education (SEARAME), 2020) Karunathilake, I.M.; Dissanayake, V.H.W.; Yasawardena, S.; Abegunawardena, A.; Raviraj, S.; Wijesinghe, P.S.; Anthony, A.A.; Wijesinghe, R.A.N.K.; Bowatte, S.; Wickramaratne, N.; Pathirana, K.D.; Pilapitiya, S.; Edirisinghe, S.; Hettiarachchi, D.; Kohombange, C.; Olipeliyawa, A.No abstract availableItem Genetic associations of inflammatory bowel disease in a South Asian population(Baishideng Publishing Group, 2018) Niriella, M.A.; Liyanage, I.K.; Kodisinghe, S.K.; Silva, A.P.; Rajapakshe, N.; Nanayakkara, S.D.; Luke, D.; Silva, T.; Nawarathne, M.; Peiris, R.K.; Kalubovila, U.P.; Kumarasena, S.R.; Dissanayake, V.H.W.; Jayasekara, R.W.; de Silva, H.J.AIM: To estimate prevalence and phenotypic associations of selected inflammatory bowel disease (IBD)-associated genetic variants among Sri Lankan patients. METHODS: A case study of histologically confirmed ulcerative colitis (UC) or Crohn's disease (CD) patients with ≥ 1 year disease duration, who were compared to unrelated, gender-matched, healthy individuals as controls, was conducted at four major centers in Sri Lanka. Phenotypic data of the cases were obtained and all participants were genotyped for 16 selected genetic variants: IL12B:rs1045431, IL23R:rs11805303, ARPC2:rs12612347, IRGM:rs13361189, IL26/IL22:rs1558744, CDH1:rs1728785, IL10:rs3024505, FCGR2A:rs3737240, PTGER4:rs4613763, IL17REL/PIM3:rs5771069, HNF4a:rs6017342, STAT3:rs744166, SMURF1:rs7809799, LAMB1:rs886774, HLA-DRB5, DQA1, DRB1, DRA:rs9268853, MST1, UBA7, and APEH:rs9822268. The genotypes of all variants were in Hardy-Weinberg Equilibrium (P > 10-3). To account for multiple hypothesis testing, P-values < 0.003 were considered significant. RESULTS: A total of 415 patients and 465 controls were recruited. Out of the single nucleotide polymorphisms (SNPs) tested, the majority were not associated with IBD in Sri Lankans. Significant positive associations were noted between rs886774 (LAMB1-gene) and UC (odds ratio (OR) = 1.42, P = 0.001). UC patients with rs886774 had mild disease (OR = 1.66, P < 0.001) and remained in remission (OR = 1.48, P < 0.001). A positive association was noted between rs10045431 (IL 12B gene) and upper gastrointestinal involvement in CD (OR = 4.76, P = 0.002). CONCLUSION: This confirms the heterogeneity of allelic mutations in South Asians compared to Caucasians. Most SNPs and disease associations reported here have not been described in South Asians.Item The Pattern of KRAS mutations in metastatic colorectal cancer: a retrospective audit from Sri Lanka(Biomed Central, 2017) Sirisena, N.D.; Deen, K.I.; Mandawala, D.E.N.; Herath, P.; Dissanayake, V.H.W.Activating mutations in the KRAS gene, found in approximately 53% of metastatic colorectal cancer (mCRC) cases, can render epidermal growth factor receptor (EGFR) inhibitors ineffective. Regional differences in these mutations have been reported. This is the first study which aims to describe the pattern of KRAS mutations in a Sri Lankan cohort of mCRC patients. RESULTS: The KRAS genotypes detected in mCRC patients which have been maintained in an anonymized database were retrospectively analyzed. Of the 108 colorectal tissue samples tested, 25 (23.0%) had KRAS mutations. Overall, there were 68 (63.0%) males and 40 (37.0%) females. Among the KRAS positive cases, there were 14 (56.0%) males and 11 (44.0%) females. Their age distribution ranged from 29 to 85 years with a median age of 61 years. There were 15 patients (60.0%) with point mutations in codon 12 while 10 (40.0%) had a single mutation in codon 13. The most common KRAS mutation identified was p.Gly13Asp (40.0%), followed by p.Gly12Val (24.0%). Other mutations included p.Gly12Cys (12.0%), p.Gly12Ser (12.0%), p.Gly12Asp (8.0%), and p.Gly12Arg (4.0%). The codon 13 mutation was a G>A transition (40.0%), while G>T transversions (32.0%), G>A transitions (24.0%), and G>C transversions (4.0%) were found in the codon 12 mutations. The frequency of KRAS mutations was similar to that reported for Asian patients. However, in contrast to several published studies, the G>A transition in codon 12 (c.35G>A; p.Gly12Asp), was not the most common mutation within codon 12 in our cohort. This may be a reflection of the genetic heterogeneity in the pattern of KRAS mutations in mCRC patients but valid conclusions cannot be drawn from these preliminary findings due to the small size of the study sample.Item Variants of ACAN are associated with severity of lumbar disc herniation in patients with chronic low back pain(Public Library of Science, 2017) Perera, R.S.; Dissanayake, P.H.; Senarath, U.; Wijayaratne, L.S.; Karunanayake, A.L.; Dissanayake, V.H.W.INTRODUCTION: Disc herniation is a complex spinal disorder associated with disability and high healthcare cost. Lumbar disc herniation is strongly associated with disc degeneration. Candidate genes of the aggrecan metabolic pathway may associate with the severity of lumbar disc herniation. OBJECTIVES: This study evaluated the association of single nucleotide variants (SNVs) of the candidate genes of the aggrecan metabolic pathway with the severity of lumbar disc herniation in patients with chronic mechanical low back pain. In addition, we assessed the in-silico functional analysis of the significant SNVs and association of their haplotypes with the severity of lumbar disc herniation. METHODS: A descriptive cross sectional study was carried out on 106 patients. Severity of disc herniation and disc degeneration were assessed on T2-weighted mid sagittal lumbar MRI scan. Sixty two exonic SNVs of ten candidate genes of aggrecan metabolic pathway (ACAN, IL1A, IL1B, IL6, MMP3, ADAMTS4, ADAMTS5, TIMP1, TIMP2 and TIMP3) were genotyped on a Sequenom MassARRAY iPLEX platform. Multivariable linear regression analysis was carried out using PLINK 1.9 software adjusting for age, gender, body mass index and severity of disc degeneration. Four online bioinformatics tools (Provean, SIFT, PolyPhen and Mutation Taster) were used for in-silico functional analysis. RESULTS: Mean age was 52.42 ± 9.42 years and 69.8% were females. The mean severity of disc herniation was 2.81 ± 1.98. The rs2272023, rs35430524, rs2882676, rs2351491, rs938609, rs3825994, rs1042630, rs698621 and rs3817428 variants and their haplotypes of ACAN were associated with the severity of lumbar disc herniation. However, only the rs35430524, rs938609 and rs3817428 variants of ACAN were detected as pathogenic by in-silico functional analysis. CONCLUSIONS: SNVs of ACAN and their haplotypes are associated with the severity of lumbar disc herniation. Functional genetic studies are necessary to identify the role of these significant SNVs in the pathogenesis of disc herniation.Item Associations between disc space narrowing, anterior osteophytes and disability in chronic mechanical low back pain: a cross sectional study(BioMed Central, 2017) Perera, R.S.; Dissanayake, P.H.; Senarath, U.; Wijayaratne, L.S.; Karunanayake, A.L.; Dissanayake, V.H.W.BACKGROUND: Radiographic features of lumbar disc degeneration (LDD) are common findings in patients with chronic mechanical low back pain; however, its role in disability and intensity of pain is debatable. This study aims to investigate the associations of the x-ray features of LDD and lumbar spondylolisthesis with severity of disability and intensity of pain. METHODS: A cross-sectional study was conducted on 439 patients with chronic mechanical low back pain who attended the rheumatology clinic, National Hospital of Sri Lanka, Colombo, from May 2012 to May 2014. Severity of disability was measured using Modified Oswestry Disability Index and intensity of pain was assessed using numeric rating scale (0-100). X-ray features of LDD (disc space narrowing, anterior osteophytes and overall LDD) and spondylolisthesis were assessed in lateral recumbent lumbar x-rays (L1/L2 to L5/S1) and graded by a consultant radiologist blinded to clinical data. Generalised linear model with linear response was used to assess the associations of x-ray features of LDD with severity of disability and intensity of pain adjusting for age, gender, body mass index and pain radiating into legs. RESULTS: Mean age was 48.99 ± 11.21 and 323 (73.58%) were females. 87 (19.82%) were obese. Mean severity of disability was 30.95 ± 13.67 and mean intensity of pain was 45.50 ± 20.37. 69 (15.72%), 26 (5.92%) and 85 (19.36%) patients had grade 2 disc space narrowing, anterior osteophytes and overall LDD, respectively. 51 (11.62%) patients had lumbar spondylolisthesis. Grade of disc space narrowing and overall LDD were not associated with severity of disability or intensity of pain. The presence of lumbar spondylolisthesis was associated with severity of disability. Female gender and pain radiating into legs were associated with severity of disability and intensity of pain. Advancing age was associated with x-ray features of LDD and lumbar spondylolisthesis. CONCLUSIONS: Lumbar spondylolisthesis is associated with severity of disability in patients with chronic mechanical low back pain. Associations of x-ray features of LDD with severity of disability and intensity of pain are inconclusive. Female gender and pain radiating into legs are significant confounders.