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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Detection of micrometastasis in LYMPH nodes using reverse transcription polymerase chain reaction (RT-PCR) for Cytokeratin 20 (CK-20): are we under staging rectal cancer(The College of Surgeons of Sri Lanka and SAARC Surgical Care Society, 2003) Wijesuriya, S.R.E.; Kuruppuarachchi, K.O.R.; Deen, K.I.; Weerasinghe, A.; Ramesh, R.; Hewavisenthi, J.INTRODUCTION: Postoperative adjuvant chemotherapy in rectal cancer is determined by the presence of metastases in lymph nodes. Detection of LYMPH node metastases is routinely performed by light microscopy. Conventional histology may not detect all metastases especially following neoadjuvant therapy (NAT). CK-20 is a cytokeratin known to be specific to colonic epithelium which may help detection of rectal cancer metastases in lymph nodes. OBJECTIVE: To detect micro metastases in lymph nodes in patients with rectal cancer. staged node negative by routine histology. METHODS: Mesenteric lymph nodes from patients who have undergone NAT for rectal cancer were harvested during surgery. Nodes were bisected and one half sent for Haernatoxylin and eosin (H&E) staining and evaluated by a single pathologist, while the other half was examined for CK 20 by RT-PCR. The technique was validated by testing lymph nodes with known metastases and nodes from patients without cancer. 21 lymph nodes from 6 patients (median age 46 years, range 25-55) which were negative for tumour deposits by H&E stain were assessed for micro metastases. RESULTS: All 2 l nodes which were histologically negative for metastases were positive for micro metastases (positive predictive value l 00%) whilst 2 nodes with known metastases were positive for CK-20, 3 nodes from non-cancer patients were negative for CK-20. CONCLUSION: Detection of CK-20 is accurate in identification of micro metastases of rectal cancer to lymph nodes. Assessment of nodes by H&E histology risks under staging lymph node micro metastases in rectal cancer.Item Result of trans-anal inter-sphincteric resection(taisr) combined with total mesorectal excision (ime) and colo- anal anastomosis for distal rectal cancer(The College of Surgeons of Sri Lanka and SAARC Surgical Care Society, 2003) Deen, K.I.; Rajendra, S.; Hewavisenthi, J.; Perera, M.T.P.R.; Satheesan, B.INTRODUCTION: The treatment of distal rectal cancer is controversial. Most prefer abdomino-perineal excision because of the potential for wide local clearance. Staplers have limitations in restorative resection for distal rectal cancer. OBJECTIVE: To audit the results ofcombinning TAISR with TME and handsewn colo-anal anastomosis for distal rectal cancer. METHODS: I 08 Patients (45 male, median age 59 years, range -22-87) with rectal cancer underwent abdomino-perineal resection -15 ( 14%), Hartmann's procedure - 7 (6.5%), anterior resection -39 (36%) and anterior resection or total colectomy with TAISR and colo-anal anastomosis -47 (43.5%). TAISR was undertaken for tumours between O and 7 ems from the anal verge for rectal cancer with familial polyposis. Data sought were; overall survival, local clearance (RO- clear margins; R l-at least one involved margin) and local recurrence at 24 month median follow up (range- 5 -89 months). Data in the TAISR group were compared with the rest by the test for proportions. Significance was assigned to p<0.05. RESULTS: For the entire group, operative 30-day mortality was 4.6%. Overall disease related mortality at 24 months was 18%. For the entire group, curative resection (RO) was achieved in 93(86%) { TAISR- 39 of 47 (83%) vs. resection without TAJSR- 54 of61(88.5%)- P>0.05}. Overall, local recurrence was seen in 8 (7.4%) {TAISR - 4 of 47 (8.5%) vs. resection without TAISR- 4 of 61 (6.5%). CONCLUSION: There was no significant difference in achievement of free resection margins and local recurrence, in the-short-term, employin anal inter-sphincteric resection with TME for distal rectal cancer co with resection for proximal rectai cancer. Trans-anal inter-sphincteric r with TME for distal rectal cancer is safe in trained hands and should preferred choice in surgical management of distal rectal cancer.Item Clinical outcome of patients having neo-adjuvant therapy(NAT) for rectal cancer: a case control study(The College of Surgeons of Sri Lanka and SAARC Surgical Care Society, 2003) Wijesuriya, S.R.E.; Deen, K.I.; Hewavisenthi, J.; Ratnayake, G.INTRODUCTION: From July i 999 we have employed NAT on a selective basis in the management of rectal cancer. OBJECTIVE: To explore the value of NAT in patients with rectal cancer in the short term. To study the effect of Neo Adjuvant Therapy for rectal carcinoma in the short term. METHODS: Two abdomino perineal resections and 24 anterior resections were done in the NAT group and 5 and 2 l in the no NAT group. There were 2 perioperative deaths in NAT group and one in the no NAT group (P 0.75). There were 7 Cancer related deaths in the NAT group and 6 in the no NAT group (P = l). The survival was 15 month (5 -45) for the NAT group and 16 (3 -54) for the non NAT group (P = I). There were no difference in the recurrences (2 vs 4 P ""0.67) metastasis (4 vs 4 P = 1) or complication (8 vs 2 p =0.08) abdomino perineal resections were performed in 2 patients in the NAT group and 5 in the no NAT group. Anterior resections were performed in 24 patients and 24 patients in NAT and no NAT groups. CONCLUSION: Overall there was no significant difference in the clinical out come between those given NAT and those not given.Item Histopathology reporting in colorectal cancer: a proforma improves quality(Wiely-Blackwell, 2009) Siriwardana, P.N.; Pathmeswaran, A.; Hewavisenthi, J.; Deen, K.I.AIM: The histopathology report is vital to determine the need for adjuvant therapy and prognosis in colorectal cancer (CRC). Completeness of those in text format is inadequate. This study evaluated the improvement of quality of histopathology reports following the introduction of a template proforma, based on standards set by the Royal College of Pathologists (RCP), UK. METHOD: Sixty-eight consecutive histopathology reports based on 19 items for rectal cancer (RC) and 15 items for colon cancer (CC) using the proforma were prospectively analysed and compared with results of a previous audit of 82 consecutive histopathology reports in text format. The percentage of reports containing a statement for each data item for both series was compared using the Normal test for difference between two proportions. Completeness of each report was assessed and a percentage score (percentage completeness) was given. Mean percentage completeness was calculated for each format and compared using the two sample t-test. RESULTS: Except for comments on the presence of 'histologically confirmed liver metastases' in CC and RC, 'distance from dentate line' and 'distance to circumferential margin' in RC, all other items were commented in more than 90% of reports, where 71% of the items based on the minimum data set were present in all reports. Compared to prose format, the mean percentage completeness (SD) improved from 74% (8) to 91% (4) (P < 0.0001) and from 81% (5) to 99% (1) (P < 0.0001) for RC and CC respectively in template proforma format. CONCLUSION: A template proforma and surgeon's contribution in relation to operative findings improves the quality of the histopathology report in CRC.Item Clinical features and treatment outcomes in patients with symptoms of irritable bowel syndrome (IBS) with and without non-specific colitis (NSC) on histology(Sri Lanka Medical Association, 2003) de Silva, H.J.; Navaratne, N.M.D.; Hewavisenthi, J.BACKGROUND: Routine rectal biopsies in patients with IBS symptoms often show histological changes of NSC. The aetiology and pathogenesis of NSC are unclear, and there are no guidelines for treatment. OBJECTIVE: To determine clinical features and treatment outcomes in patients with IBS symptoms with and without NSC on rectal or colonic biopsies. METHODS: Consecutive patients attending an out-patient clinic diagnosed as having IBS using ROME II criteria were further studied. They all had a clinical assessment, and routine stools examination and culture, flexible sigmoidoscopy and barium enema or colonoscopy with biopsy. Patients who had normal rectal/ colonic histology (NHIBS) or NSC were given treatment for IBS symptoms with dietary modification, anti-spasmodics, anti-diarrhoeals, and anti-depressants, alone or in combination. Response to treatment was assessed after three months. RESULTS: 75 patients (M;- F=50:25; mean age 35.9 years) who had IBS symptoms and normal stool examination and large bowel endoscopy/ radiology were followed up. Six (one with ulcerative colitis, 5 with lymphocytic colitis) were excluded after rectal histology. Patients with NHIBS (n=29) and NSC (n=40) were well matched for age, gender and duration of symptoms. After 3 months of treatment for IBS symptoms, the response to treatment was similar in the two groups (NIBS Vs. 20, worsening 7 Vs 8). CONCLUSIONS; NSC is frequently seen in patients presenting with IBS symptoms. The clinical significance of this finding is unclear, as clinical features and short-term response to symptomatic treatment is similar to patients with BHIBS.Item The detection of the expression of Keratin 19 and Keratin 20 genes in the diagnosis of micrometastases of colonic cancers(Sri Lanka Medical Association, 2003) Weerasinghe, A.; Kuruppuarachchi, G.; Wijesuriya, R.; Hewavisenthi, J.; Deen, K.I.OBJECTIVE: Keratin 19(K-19) and Keratin 20(K-20) genes are expressed in the epithelial tissues while they are absent in lymphoid-tissues. Therefore the expression of these foreign genes in lymph nodes is used in the diagnosis of micrometastases. We investigated the expression of K19 and K2C in the diagnosis of micrometastases of colonic cancer. DESIGN, SETTING AND METHODS: Regional lymph nodes of patients with colonic cancer (n = 5) were obtained from University Surgical Unit of Ragama. Two corresponding lymph nodes from non-cancer patients and colonic tumor tissue were used as negative and positive control respectively. De-ionized water was used as blank control. Lymph nodes were collected directly to the RNA extracting media (Isogen) during the surgery. Specimens were transported to Medical Research Institute within one hour at 4 C. cDNA was synthesized using reverse transcriptase and K19 and K20 primers were used to detect the expression of these genes. PCR products were identified using agarose gel electrophoresis after amplification using the thermal cycler (Perkin Elmer). (3-actin primer was used for internal quality control. RT/PCR findings were compared with the routine histological findings of the patients. RESULTS: Lymph nodes of all five patients with colonic cancers and the colonic cancer tissues were positive for the expression of K19 and K 20. Both control lymph nodes were negative for the expression of K-19 and K-20. All the patients with colonic cancers were negative on histology of the lymph node biopsies. CONCLUSION: These findings suggest that the detection of the expression of K19 and K20 help to identify the metastases, which are negative on histology.Item Views of students on the use of computer aided pathology practical classes(Sri Lanka Medical Association, 2012) Mahendra, B.A.G.G.; Rathnayake, R.M.U.S.; Hewavisenthi, J.INTRODUCTION: Conducting pathology practical classes in the traditional manner is becoming increasingly difficult With rapidly advancing medical knowledge it is a challenge to impart a large amount of facts within a limited time. A programme of Computer Aided Pathology Practicals (CAPP) was introduced to overcome these challenges. AIMS: To determine whether this programme was successful in the view of the students, what the short comings were, and how the system could be improved. METHODS: A self administered questionnaire was used to assess the views of the students of Batch 20 of the Medical Faculty, Kelaniya. The pathology practicals for these students had been conducted using both the traditional and the CAPP systems. Results: 62.7 % students preferred the CAPP programme. The reasons offered for this preference included greater enhancement of knowledge of the course content [59.6% ), a greater area of knowledge covered within a single session (76.9%], ability to appreciate the architectural (73.4%) and cytological features ( 76.8%) of lesions better, being easier to operate (77%) and the saving of time ( 85.7%). However 67.9% of the students were of the opinion that the traditional pathology practicals were more realistic especially with regard to appreciating the macroscopic features, than the CAPP system. CONCLUSIONS: Overall the CAPP programme was well received by a majority of students. The lack of "hands on experience" is a problem encountered in all forms of virtual teaching. This could be improved by encouraging the students to use the pathology museum more frequently.Item Distribution of human papillomavirus genotypes in archival cervical tissue from women with cervical cancer in urban Sri Lanka(Elsevier, 2011) Samarawickrema, N.A.; Tabrizi, S.N.; Hewavisenthi, J.; Leong, T.; Garland, S.M.OBJECTIVE: To identify the contributions of various human papillomavirus (HPV) genotypes in tissue samples from women diagnosed with cervicalcancer in Sri Lanka. METHODS: In a retrospective study, archival cervical tissues samples (n=108) obtained from Sri Lankan women diagnosed with histologically proven invasive squamous cell carcinoma between 2006 and 2007 were tested for HPV. Genotyping of HPV DNA was performed using an INNO-LiPA assay. RESULTS: Overall, 93% of tumor samples tested positive for HPV DNA. HPV types 16 and 18 accounted collectively for 83.4% of the positive samples. CONCLUSION: The findings suggest that the HPV genotypes responsible for causing cervical cancer in Sri Lanka are similar to those reported elsewhere worldwide. Consequently, women in Sri Lanka could benefit from currently available prophylactic HPV vaccines should they be implemented.Item Comparison of one and two weeks of triple therapy for eradication of H. pylori: a randomized, controlled study in a tropical country(Wiley Blackwell Scientific Publications, 2004) de Silva, H.A.; Hewavisenthi, J.; Pathmeswaran, A.; Navarathne, N.M.M; Peiris, R.; Dassanayake, A.S.; de Silva, H.J.INTRODUCTION: Resistance of H. pylori to antibiotics may be particularly high in parts of the tropics. Infection may prove difficult to eradicate in such situations, and there is some evidence of benefit in increasing duration of treatment (triple therapy) from one week to two or three weeks. AIM : To assess the efficacy and tolerability of one-week versus two weeks triple therapy for eradication of H. pylori in a Sri Lankan population. METHODS: 82 consecutive patients aged 18–70 years with peptic ulcer disease testing positive for H. pylori infection (histology and rapid urease test on gastric antral biopsies) were randomly allocated to two treatment groups. The baseline characteristics of the two groups were similar. Both groups received omeprazole 20mg, clarithromycin 250mg, and tinidazole 500mg. Group A (n = 42) received the trial medication twice daily for one week and the Group B (n = 40) twice daily for two weeks. H. pylori eradication was defined as a negative 14C labeled urea breath test at two weeks after completion of therapy. The assessors were blind to randomization and other patient information. RESULTS; All patients presented for follow up after completion of therapy. H. pylori infection was eradicated in 36 (85.7%) patients in group A and 36 (90%) patients in group B (p = 0.9; 95% CI: -19.1 to 10.8). 23 (55%) patients in group A and 17 (43%) in group B reported adverse effects attributable to trial medication (p = 0.387); none were serious. 3 (7.5%) patients in group B discontinued treatment due to adverse events that developed on days 7, 9 and 10. CONCLUSION: Twice daily treatment with clarithromycin, tinidazole, and omeprazole for one-week is well tolerated and provides as good a rate of H. pylori eradication as two weeks therapy in Sri Lankan patients.Item Subclinical intestinal mucosal inflammation in diarrhoea predominant irritable bowel syndrome in a tropical setting(Sri Lanka Medical Association, 2010) de Silva, A.P.; Mannamperi, A.; Ariyasinghe, M.P.; Nandaslri, A.S.D.; Hewavisenthi, J.; Dassanayake, A.S.; Jewell, D.P.; de Silva, H.J.OBJECTIVES: There has been increasing evidence to support an inflammatory pathology in irritable bowel syndrome (IBS), especially diarrhoea predominant type (IBS-D).The aim of this study was to investigate for evidence of intestinal mucosal inflammation in IBS-D in a tropical setting. METHODS: In a prospective study over one year, we investigated 49 patients with IBS-D [median age 34 years (range 18-59; M: F 36:13], based on Rome III criteria and 14 controls [median age 46.5 years (range 23-56); M: F 6:8]. None had alarm symptoms, were on NSAIDS or PPIs. All patients had normal ESR, CRP, TSH and stools reports. Stools of all subjects were tested for calprotectin. During colonoscopy, serial biopsies were obtained.Tissue expression of IL-8 and IL-10 were assessed in biopsy specimens using semi-quantitative RT-PCR. RESULTS: Colono-ileoscopy was macroscopically normal and faecal calprotectin was undetectable in cases and controls. Microscopic colitis not otherwise specified (MNOS) was seen in 10/49 cases and 1/14 controls (p=0.43, Fisher's Exact test). A history suggestive of an episode of infectious diarrhoea (ID) was seen in 16/49 cases and 0/14 controls (p=0.013). Tissue expression of IL-8 was significantly higher and IL-10 significantly lower in cases compared to controls (target/standard cDNA ratio, median (range) IL-8: 1.25 (0.75-2) vs 0.85 (0.63-1.37), p<0.0001, Mann-Whitney U test; IL-10: 0.33 (0-0.63) vs 0.55 (0.5-0.7), p<0.0001). There was a significant inverse correlation between IL-8 and IL-10 expression (Pearson Correlation, (-) 0.509; p<0.01). CONCLUSIONS: There is evidence for sub-clinical intestinal mucosal inflammation in patients with IBS-D in a tropical setting, whether a history of ID or MNOS was present or absent.
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