Browsing by Author "Jayasekara, R.W."

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Changing phenotype, early clinical course and clinical predictors of inflammatory bowel disease in Sri Lanka: a retrospective, tertiary care-based, multi-centre study
(BioMed Central, 2021) Niriella, M.A.; Liyanage, I.K.; Kodisinghe, S.K.; de Silva, A.P.; Jayatissa, A.V.G.A.M.; Navarathne, N.M.M.; Peiris, R.K.; Kalubovila, U.P.; Kumarasena, S.R.; Jayasekara, R.W.; de Silva, H.J.
BACKGROUND: Inflammatory bowel disease (IBD) is increasing in the Asia-Pacific region, with changes in disease phenotype and course. We aimed to assess the changing phenotypes of IBD over ten years, describe the early clinical course (ECC) and identify the clinical predictors (CP) of poor outcomes among a large, multi-centre, cohort of Sri Lankan IBD patients. METHODS: We included patients [diagnosed between June/2003-December/2009-Group-1(G1), January/2010-June/2016-Group-2(G2)] with ulcerative colitis (UC) and Crohn disease (CD) from five national-referral centres. Changing phenotype from G1 to G2, ECC (disease duration < 3-years) and CP of poor outcomes (disease duration ≥ 1-year) was assessed. Poor outcomes were complicated-disease (CompD-stricturing/penetrating-CD, extensive-UC/pancolitis, perforation/bleeding/colectomy/malignancy) and treatment-refractory disease (TRD-frequently-relapsing, steroid-dependent/refractory and biologic use). RESULTS: 375 (UC-227, CD-148) patients were recruited. Both G1/G2 had more UC than CD (77% vs 23%, 54.5 vs 45.5 respectively, p < 0.01). Increase of CD from G1-to-G2 was significant (23-45.4%, p < 0.001). In both groups, left-sided colitis (E2) and ileo-colonic (L3)/non-stricturing, non-penetrating disease behaviour (B1) CD predominated. Extensive-colitis (E3) (36.4% vs 22.7, p < 0.05) and stricturing-CD (B2) (26.1% vs 4.0%, p < 0.01) was commoner in G1. ECC was assessed in 173-patients (UC-94, CD-79). Aggressive disease behaviour and TRD were low among both UC and CD. Immunomodulator use was significantly higher among CD than UC (61.5% vs 29.0% respectively, p < 0.01). Anti-TNF use was low among both groups (UC-3.2%, CD-7.7%). Disease complications among UC [bleeding (2.1%), malignancy-(1.1%), surgery-(2.1%)] and CD [stricture-(3.9%), perforation-(1.3%), malignancy-(1.3%), surgery-(8.9%)] were generally low. CPs were assessed in 271-patients (UC-163, CD-108). Having a family history of IBD (for UC), extraintestinal manifestation (EIM), severe disease at presentation, being in younger age categories and severe disease at presentation, (for both UC and CD) predicted poor outcomes. CONCLUSION: There was an increase in CD over time without change in disease phenotype for both UC and CD. A relatively benign ECC was observed. Family history (UC), EIMs (UC/CD), severe disease at presentation (UC/CD), younger age (CD/UC) CPs of poor outcomes. KEYWORDS: Clinical course; Clinical predictors; Crohn disease; Inflammatory bowel disease; Phenotype; Sri Lanka; Ulcerative colitis.
Changing phenotype, early clinical course and clinical predictors of irritable bowel syndrome in Sri Lanka: a prospective, multi-centre descriptive study
(Sri Lanka Medical Association, 2017) Niriella, M.A.; Kodisinghe, S.K.; Nanayakkara, S.D.; Silva, K.T.M.; Rajapakshe, N.; Luke, D.; de Silva, A.P.; Navarathne, N.M.M.; Dissanayake, V.H.W.; Jayasekara, R.W.; de Silva, H.J.
INTRODUCTION & OBJECTIVES: Incidence of inflammatory bowel disease (IBD) is increasing in the Asia Pacific, with changes in phenotype and disease course been reported. METHODS: Ulcerative colitis (UC) and Crohn disease (CD) cases from four national referral centres were included. Phenotype was compared for cases [Group-1/G1-diagnosed between June/2003-December/2009, Group-2/G2-January/2010-June/2016]. Early clinical course (ECC) [complicated disease (Comp D-stricturing/penetrating CD, extensive-UC/pancolitis), treatment refractory disease (TRD-frequently-relapsing, steroid-dependent/refractory, biologics), disease complications (DC-perforation/bleeding/colectomy/malignancy)] among disease duration <3 years, and clinical predictors (CP) of CompD/TRD/DC among disease duration >1 year were also assessed. RESULTS: A total of 452-cases [G1: UC-89 (78.8%), CD-24 (21.2%); G2: UC-197 (58.1%), CD-142 (41.9%)] were included. G2 had a higher proportion of CD (p<0.001). In both groups, leftsided colitis (E2) for UC, ileo-colonic (L3)/non-stricturing, non-penetrating (B1) for CD predominated. More penetrating-CD (B3) in G2 (p<0.01) and more stricturing-CD (B2) in G1 (p<0.05) were noted. ECC was assessed in 293 patients [UC-168 (57.3%), CD-125 (42.7%)]. Among UC: extensive/pan-colitis (E3)-40 (24.5%), severe (S3)-38 (42.2%); among CD:severe episodes-15 (25.9%), stricturing (B2)/penetrating(B3)-18 (14.7%), perianal-disease (P)-29 (23.4%). TRD was seen in 19 (11.3%)-UC and 17 (10.1%)-CD. Immunomodulator use was-70 (41.7%)/93 (74.4%), and anti-TNF use was 3 (1.8%)/12 (9.6%) respectively for UC and CD. Complications for UC: bleeding-6 (3.6%), malignancy-1 (0.6%), surgery-3 (1.8%); for CD: stricture-6 (4.9%), perforation-3 (2.4%), malignancy-1 (0.8%), surgery-2 (1.6%). CP were assessed in 373 [UC-266 (71.3%), CD 107 (28.7%)]. EIM of joints predicted CompD in UC/CD (OR-1.94/OR-2.28). Family history (OR=8.64) and EIM of joints (OR=10.07) predicted DC in UC. CONCLUSION: There was an increase in CD during the study period, but no changes in disease phenotype for UC or CD. Although admissions with CompD were common for UC (but not CD), few patients had TRD or DCs indicating a relatively benign early disease course. Family history, EIM of joints predicted poor outcomes in UC, EIM of joints predicted a poor outcome in CD.
Clinical exome gene panel analysis of a cohort of urothelial bladder cancer patients from Sri Lanka
(Asian Pacific Organization for Cancer Prevention, 2023) Malalasekera, A.; Neththikumara, N.; Somasundaram, P.; Pathirana, S.; Ediriweera, C.; Ediriweera, D.; Goonewardena, S.A.; Perera, N.D.; Abeygunasekara, A.; Jayasekara, R.W.; Wettasinghe, K.; Lokuhetty, M.D.S.; Dissanayeke, V.H.W.
BACKGROUND: Bladder cancer has a high rate of recurrence and high mortality rates in those who progress to muscle invasive disease. Biomarkers and molecular sub classification of tumours beyond standard histopathology has been proposed to address therapeutic dilemmas. The Cancer Genome Atlas project and other studies have contributed to the enhanced knowledge base of the mutational landscape of urothelial bladder cancer. Once again, these are mostly from Caucasian and Chinese patients, with data from the rest of Asia and Sri Lanka being sparse. The objective of this study was to assess the genomic variations of a cohort of urothelial bladder cancer patients in Sri Lanka. METHODS: The molecular genetic study was conducted on formalin fixed paraffin embedded tumour samples of 24 patients, prospectively enrolled from 2013 to 2017. The samples were sequenced and variant distribution performed based on a 70-gene panel. RESULTS: Total number of filtered mutations in the 24 patients was 10453. Median mutations per patient were 450 (range 22-987). The predominant mutational change was C>T and G>A. The top 5 mutated genes in our cohort were SYNE1, SYNE2, KMT2C, LRP2, and ANK2. The genes were clustered into 3 groups dependent on the number of mutations per patient per gene. The genes of cluster 1 and 2 mapped to Chromatin modifying enzymes and Generic Transcription Pathway. The chromatin remodelling pathway accounted for the largest proportion (22%) of mutations. CONCLUSIONS: Clinical exome sequencing utilising a gene panel yielded a high mutation rate in our patients. The predominant mutational change was C>T and G>A. Three clusters of genes were identified. SYNE1 was the gene with the most mutations. The mutations comprised predominantly of genes of the chromatin remodelling pathway.
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.
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.
Meta-analysis of global variations in grade of pT1 urothelial bladder cancer and supplementary evaluation of a Sri Lankan cohort
(The College of Surgeons of Sri Lanka, 2022) Malalasekera, A.P.; Ediriweera, D.; Goonewardena, S.; Perera, N.; Abeygunasekara, A.; Jayasekara, R.W.; Wettasinghe,T.K.; Dissanayake,V.H.W.D.; Lokuhetty, M.D.S.
Introduction Bladder cancer grading is fraught with ambiguity. We aimed to conduct a meta-analysis of grading of pT1 urothelial cancers and assess histopathology and outcomes in a Sri Lankan pT1 bladder cancer cohort. Patients and Method A meta-analysis of grading of pT1 urothelial cancers was conducted as per PRISMA guidelines. A second metaanalysis of the proportion of pTa/NMIBC at disease presentation was conducted to assess impact of delayed presentation on grading. Analysis was supplemented with data from a cohort of Sri Lankan patients. Results In the meta-analysis, the overall pooled pT1 HG prevalence was 75.3% [95% CI:68.3%-81.7%]. The pT1 HG prevalence was significantly higher (p=4.916878e-11) among the European, Japanese and Taiwanese studies at 90.1% [95% CI: 85.3%-94.0%] compared to the rest of the countries at 56.1% [95% CI:46.5%-65.4%]. The overall pooled pTa/NMIBC prevalence was 44.2% [95% CI:36.4%-52.1%]. The pTa/NMIBC percentage among Europe, China and Taiwan was 66.9%[95% CI:62.4%-71.2%] and it was 37.6% [95% CI:29.0%-46.6%] in Turkey and other Asian countries indicating a significant difference(P=1.08e-08). In the Sri Lankan cohort of 66 enrolled patients, 31(47%) had pT1, of which 61% were low-grade (LG). The 5-year progressionfree survival (PFS) of pT1 was 60.9%. In LG it was 85.7% and 22.2% in high-grade (HG) (P = 0.0006). Conclusion There is a global variation of percentages of pT1 LG versus HG disease in bladder cancer specimens at presentation which could be attributed to delay in treatment with stage migration, ethnic variations in tumour biology, and interobserver variability in assigning a grade of tumour, and needs further study.