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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Proximal and distal rectal cancers differ in curative resectability and local recurrence(Baishideng Publishing Group, 2011) Wijenayake, W.; Perera, M.; Balawardena, J.; Deen, R.; Wijesuriya, S.R.; Kumarage, S.K.; Deen, K.I.AIM: To evaluate patients with proximal rectal cancer (PRC) (> 6 cm up to 12 cm) and distal rectal cancer (DRC) (0 to 6 cm from the anal verge). METHODS: Two hundred and eighteen patients (120 male, 98 female, median age 58 years, range 19- 88 years) comprised 100 with PRC and 118 with DRC. The proportion of T1, T2 vs T3, T4 stage cancers was similar in both groups (PRC: T1+T2 = 29%; T3+T4 = 71% and DRC: T1+T2 = -31%; T3+T4 = 69%). All patients had cancer confined to the rectum - those with synchronous distant metastasis were excluded. Surgical resection was with curative intent with or without preoperative chemoradiation (c-RT). Follow-up was for a median of 35 mo (range: 12 to 126 mo). End points were: 30 d mortality, complications of operation, microscopic tumour- free margins, resection with a tumourfree circumferential margin (CRM) of 1 to 2 mm and > 2 mm, local recurrence, survival and the permanent stoma rate. RESULTS: Overall 30-d mortality was 6% (12): PRC 7 % and DRC 4%. Postoperative complications occurred in 14% with PRC compared with 21.5% with DRC, urinary retention was the complication most frequently reported (PRC 2% vs DRC 9%, P = 0.04). Twelve percent with PRC compared with 37% with DRC were subjected to preoperative c-RT (P = 0.03). A tumour-free CRM of 1 to 2 mm and > 2 mm was reported in 93% and 82% with PRC and 88% and 75% with DRC respectively (PRC vs DRC, P > 0.05). However, local recurrence was 5% for PRC vs 11% for DRC (P < 0.001). Three and five years survival was 65.6% and 60.2% for PRC vs 67% and 64.3% for DRC respectively. No patient with PRC and 23 (20%) with DRC received an abdomino-perineal resection. CONCLUSION: PRC and DRC differ in the rate of abdomino-perineal resection, post-operative urinary retention and local recurrence. Survival in both groups was similar.Item Young patients with colorectal cancer have poor survival in the first twenty months after operation and predictable survival in the medium and long-term: analysis of survival and prognostic markers(BioMed Central, 2010) Chan, K.K.; Dassanayake, B.; Deen, R.; Wickramarachchi, R.E.; Kumarage, S.K.; Samita, S.; Deen, K.I.OBJECTIVES: This study compares clinico-pathological features in young (<40 years) and older patients (>50 years) with colorectal cancer, survival in the young and the influence of pre-operative clinical and histological factors on survival. MATERIALS AND METHODS: A twelve-year prospective database of colorectal cancer was analysed. Fifty-three young patients were compared with forty-seven consecutive older patients over fifty years old. An analysis of survival was undertaken in young patients using Kaplan Meier graphs, non-parametric methods, Cox's Proportional Hazard Ratios and Weibull Hazard models. RESULTS: Young patients comprised 13.4 percent of 397 with colorectal cancer. Duration of symptoms and presentation in the young was similar to older patients (median, range; young patients; 6 months, 2 weeks to 2 years, older patients; 4 months, 4 weeks to 3 years, p > 0.05). In both groups, the majority presented without bowel obstruction (young--81%, older--94%). Cancer proximal to the splenic flexure was present more in young than in older patients. Synchronous cancers were found exclusively in the young. Mucinous tumours were seen in 16% of young and 4% of older patients (p < 0.05). Ninety-four percent of young cancer deaths were within 20 months of operation. At median follow up of 50 months in the young, overall survival was 70% and disease free survival 66%. American Joint Committee on Cancer (AJCC) stage 4 and use of pre-operative chemoradiation in rectal cancer was associated with poor survival in the young. CONCLUSION: If patients, who are less than 40 years old with colorectal cancer, survive twenty months after operation, the prognosis improves and their survival becomes predictable.Item Complete migration of a composite mesh into small bowel incidentally found during laparotomy for colectomy in an asymptomatic patient: a case report(BioMed Central, 2020) Chandrasinghe, P.; de Silva, A.; Welivita, A.; Deen, K.I.BACKGROUND: Composite meshes are used for incisional hernia repair because they enable intraperitoneal mesh placement due to their dorsal surface, which is made of inert material. We report, for the first time, to our knowledge, a case of composite mesh migration detected incidentally during a laparotomy for colon cancer in an asymptomatic patient. CASE PRESENTATION: Our patient was a 71-year-old South Asian man who underwent ventral mesh repair following a postoperative complication after right hemicolectomy for colon cancer. The patient was diagnosed with a metachronous sigmoid cancer 5 years later, for which he underwent laparotomy. During laparotomy, a migrated mesh was incidentally found and extracted from his proximal ileum without any evidence of abscess or fistula formation. CONCLUSION: To our knowledge, this is the first report of an incidentally found migrated composite mesh from a bowel lumen in an asymptomatic patient. KEYWORDS: Case report; Composite mesh; Mesh complications; Mesh migration.Item Colorectal cancer burden and trends in a South Asian cohort: experience from a regional tertiary care center in Sri Lanka(Biomed Central, 2017) Chandrasinghe, P.C.; Ediriweera, D.S.; Hewavisenthi, J.; Kumarage, S.K.; Fernando, F.R.; Deen, K.I.OBJECTIVE: Colorectal cancer (CRC) burden is increasing in the south Asian region due to the changing socio-economic landscape and population demographics. There is a lack of robust high quality data from this region in order to evaluate the disease pattern and comparison. Using generalized linear models assuming Poisson distribution and model fitting, authors describe the variation in the landscape of CRC burden along time since 1997 at a regional tertiary care center in Sri Lanka. RESULTS: Analyzing 679 patients, it is observed that both colon and rectal cancers have significantly increased over time (pre 2000-61, 2000 to 2004-178, 2005 to 2009-190, 2010 to 2014-250; P < 0.05). Majority of the cancers were left sided (82%) while 77% were rectosigmoid. Over 25% of all CRC were diagnosed in patients less than 50 years and the median age at diagnosis is < 62 years. Increasing trend is seen in the stage at presentation while 33% of the rectal cancers received neoadjuvant chemoradiation. Left sided preponderance, younger age at presentation and advanced stage at presentation was observed. CRC disease pattern in the South Asian population may vary from that observed in the western population which has implications on disease surveillance and treatment.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 Overall survival of elderly patients having surgery for colorectal cancer Is comparable to younger patients: results from a South Asian population(Hindawi Publishing Corporation, 2017) Chandrasinghe, P.C.; Ediriweera, D.S.; Nazar, T.; Kumarage, S.; Hewavisenthi, J.; Deen, K.I.INTRODUCTION: There has been a continuous debate on whether elderly patients with colorectal cancer (CRC) fair worse. The aim of this study is to assess the thirty-day mortality (TDM) and overall survival (OS) of elderly patients undergoing surgery for CRC. METHOD: OS between two groups (≥70 versus <70 years) having surgery for CRC was analyzed. Demographics, tumour characteristics, and serological markers were considered as independent factors. Multivariable analysis was done using the Cox proportional hazard model. We also compared overall survival in the elderly versus those <60 and <50 years. RESULTS: 477 patients, 160 elderly (55% male; median age 75, range 70-89) and 317 younger patients (49% male; median age 55, range 16 to 69), were studied. Overall survival in CRC patients ≥70 is comparable to <70 (P = 0.45) and <60 years (P = 0.08). Poor OS was observed in the ≥70 versus <50 years (P = 0.03). TDM in the elderly was poor (P < 0.05). Postoperative cardiac complication was the only determinant affecting survival in the elderly (P = 0.01). CONCLUSION: OS in elderly CRC patients having surgery is not worse compared to <70 and <60 years although the TDM was higher. Postoperative cardiac complications significantly affected OS in those ≥70 compared to those <50 years. Chronological age alone should not negatively influence surgical decision-making in the elderly.Item Postmortem sampling of the pancreas for histological examination: what is the optimum cut-off time?(iMed Pub, Washington., 2010) Siriwardana, R.C.; Deen, K.I.; Hewavisenthi, J.Item Resection of the large bowel suppresses hunger and food intake and modulates gastrointestinal fermentation(John Wiley & Sons, 2016) Hettiarachchi, P.; Wickremasinghe, A.R.; Frost, G.S.; Deen, K.I.; Pathirana, A.A.; Murphy, K.G.; Jayaratne, S.D.OBJECTIVE: To assess appetite and gut hormone levels in patients following partial (PR) or total resection (TR) of the large bowel. METHODS: A comparative cross sectional study was carried out with healthy controls (n = 99) and patients who had undergone PR (n = 64) or TR (n = 12) of the large bowel. Participants consumed a standard (720 kcal) breakfast meal at 0830 (t = 0) h followed by lactulose (15 g) and a buffet lunch (t = 210 min). Participants rated the subjective feelings of hunger at t = -30, 0, 30, 60, 120, and 180 min. Breath hydrogen (BH) concentrations were also evaluated. In a matched subset (11 controls, 11 PR and 9 TR patients) PYY and GLP-1 concentrations were measured following breakfast. The primary outcome measure was appetite, as measured using visual analogue scales and the buffet lunch. The secondary outcome was BH concentrations following a test meal. RESULTS: PR and TR participants had lower hunger and energy intake at the buffet lunch meal compared to controls. PR subjects had higher BH concentrations compared to controls and TR subjects. BH levels correlated with circulating GLP-1 levels at specific time points. CONCLUSIONS: PR or TR of the large bowel reduced feelings of hunger and energy intake, and PR increased gastrointestinal fermentation.Item The Recto-Anal Inhibitory Reflex (RAIR): abnormal response in diabetics suggests an intrinsic neuro-enteropathy(BMJ Publishing, 1997) Deen, K.I.; Premaratna, R.; Fonseka, M.M.D.; de Silva, H.J.INTRODUCTION: The recto-anal inhibitory reflex (RAIR) is characterized by reflex relaxation of the anal canal in response to electrical stimulation of the rectal mucosa, and is mediated by nitrergic neural plexuses within the gut wall. Impairment of this reflex may lead to incontinence. AIM: To measure anal canal pressures, anal mucosal electrosensation and RAIR in diabetic patients and correlate these measurements with incontinence for gas or faeces. METHODS: Anal canal pressure, RAIR and continence was evaluated in 30 diabetic patients [Male:Female=13:17, median age 57 years (range 37- 70)], and these data were compared with similar data obatained from 22 age and sex matched 'healthy' controls [Male:Female= 9:13, median age 51 years (range 19 - 65 )]. Median duration of diabetes was 8 years (range 3 -30 ). 12 (40%) of the 30 diabetics had impaired continence for gas (n=12) and liquid faeces (n=3). None ofthe controls had incontinence. RESULTS: Maximum resting anal canal pressure (MRP) was [median (range)]: Patients 30mmHg (20-75) vs. Controls 40mmHg (20-105), P=0.61. Maximum squeeze pressure (MSP) [median (range)]: Patients 65mmHg (30- 150) vs. Controls 84mmHg (35-230), P=0.59. Threshold rectal mucosal eletrosensation (RMES-T) [median (range)]: Patients 27 mA (5-40) vs. Controls l3mA (5-28), P=0.03. Maximum tolerable rectal mucosal electrosensation [median (range)]: Patients 40 mA (20-60) vs. Controls 20 mA (10-30), P=0.042 (all comparisons using Wilcoxon rank test). RAIR was present in 8, abnormal in 5 (1 with incontinence), and absent in 17 (II with incontinence) diabetics while it was present in 18 and abnormal in 4 controls (test of proportion, P=0.03 I). CONCLUSIONS: RAIR was impaired in significantly more patients with diabetes than controls implying impairment of intrinsic neuronal function. All diabetic patients with incontinence had impaired or absent RAIR. Impairment of this reflex may be a useful predictor of incontinence in diabetics.Item Comparison of hazard of death following surgery for colon versus rectal cancer(Sri Lanka Medical Association, 2016) Ediriweera, E.P.D.S.; Kumarage, S.; Deen, K.I.INTRODUCTION: Prognosis in cancer is usually assessed by use of Kaplan-Meier survival function estimate curves, which reflect survival, or the proportion of patients that will remain alive after a particular event at a given time. By contrast, hazard function represents the proportion expected to be deceased among those surviving at a given time after an event. OBJECTIVES: To evaluate survival and hazard of death, in patients with colon cancer (CC) and rectal cancer (RC), as indices of prognosis. METHODS: Colon and rectal cancer patients who underwent surgical resection with curative intent from 1996 to 2011 were studied. The hazard of death and survival patterns were assessed with Weibull Hazard models and Kaplan- Meier survival function estimate curves. RESULTS: There were 119 CC and 250 RC patients included in the study. Median (Inter-quartile range: IQR) age of both groups was 58 (49 - 66.5) years. The median (IQR) followup time was 30 (12 - 72) months for CC and 30 (13 - 70) months for RC. Both groups were similar in comparison with regard to age (p=0.96), gender (p=0.56), tumour stage (p=0.33), vascular invasion (p=0.69), lymphatic invasion (p=0.33), perineural invasion (p=0.94), degree of tumour differentiation (p=0.38) and preoperative carcinoembryonic antigen levels (p=0.77). CC showed better overall survival compared to RC (p=0.03) with a 5-year survival rate of 72% versus 60% respectively. After curative resection, CC showed a 6% decrease in hazard of death with time compared with RC which showed a 1% increase in the hazard of death with time. CONCLUSIONS: Among patients who underwent resectional surgery, CC had a better prognosis than RC.