Conference Papers

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This collection contains abstracts of conference papers, presented at local and international conferences by the staff of the Faculty of Medicine

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End date: 2019Has files: No

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    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.; Dassanayaka, 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%), radio frequency ablation or alcohol ablation in 8 (7.6%), trans arterial chemo embolization (TACE) in 44 (41.9%) and sorafmib 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.
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    Chracterisation of beta giobin mutations in Sri Lankan patients with betathalassaemia intermedia
    (Sri Lanka Medical Association, 2013) Perera, S.; Silva, D.P.S.I.; Hapugoda, M.; Wickramarathne, M.N.; Wijesirwardhena, I.; Efremove, D.G.; Fisher, C.A.; Weatherall, D.J.; Premawardhena, A.P.
    INTRODUCTION AND OBJECTIVES: Patients with beta thalassaemia intermedia account for a third of patients attending thalassaemia clinics in Sri Lanka. They show immense phenotypic diversity, the genetic basis for which has not been identified so far. Objective were to characterise beta globin gene mutations in Sri Lankan thalassaemia intermedia patients and to determine how it to influences disease severity. METHODS: We identified 64 thalassaemia intermedia patients from the five main thalassaemia centers; Anuradhapura (n= 6), Kuruncgala (n= 4), Ragama (n= 42), Badulla (n=7) and Chilaw (n=5). Their beta globin DNA sequences were analyzed using ABI PRISM 313lx genetic analyser. RESULTS: Of sixteen patients identified to be homozygous for beta mutations, eleven carried mild beta alleles, IVSI 5 G_C (n= 10) and a rare homozygous promoter mutation - 90 C_T (N=l). Other five were shown to have different types of severe iputations in homozygous state. Nearly half the sample (n=39) was heterozygous for beta mutations. Of them 33 showed mild to severe mutation in one of the alleles IVSI-5 G_C (n=12), IVSI-1 G_A (n= 11) were the commonest. Two patients who were hetcrozygones for beta mutation had a highly unstable Hb variant haemoglobin Mizuho causing severe haemolytic anacma. Hb variants Hb G-Szuhu and Hb G-Coushatta were identified in two patients. CONCLUSIONS: We identified types of beta mutations in some patients with thalassaemia intermedia, which account for the clinical severity.
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    Paraspinal extramcduallry erythropoiesis- a rare cause of spinal cord compression: two case reports
    (Sri Lanka Medical Association, 2004) Arambepola, M.; Premawardhena, A.P.; de Silva, S.; Olivieri, N.; Weatherall, D.J.
    INTRODUCTION: Extrameduallry erythropoiesis (EME) is characterized by the appearance of haemopoietic tissue outside the bone marrow. When EME occurs, albeit rarely, outside the liver and spleen problems may occur. We describe two patients with haemoglobin E- [β thalassaemia who had spinal cord compression, due to EME masses which was reversed with treatment with hydroxyurea and hypertransfusion. PATIENT A: Was a 27year old with HbE -(β thalassaemia. His mean pre transfusion haemoglobin level was 5.5 g/dl. He presented with a six-month history of progressive numbness of his legs. On examination he was found to be paraparetic. The magnetic resonance scan (MRI) showed external compression of the spinal cord between the 4th and 8th thoracic vertebrae. Patient was put on a hypertransfusion regimen and hydroxyurea and made a complete recovery within 4 weeks. Patient B: Was a 9 year old boy with a diagnosis of Haemoglobin E [β thalassaemia who presented with paraplegia which had developed over 3 months. His spinal MRI showed two masses one in the upper thoracic vertebrae and the other at the 1st lumbar level. He was commenced on hydroxyurea and hypertransfusiion to maintain pre-transfusion haemoglobin at >9.5g/dl) and his neurological recover was remarkable. Six months later he had no neurological deficit. DISCUSSION: The above cases highlight the potentially dangerous complications of EME when it involves the spinal cord. They also highlight that even lesions which are sufficiently large to cause complete paraplegia are potentially reversible. Hypertransfusion, hydroxyurea, surgery and previously been used with varying success. The problem remains in deciding the optimal method of management.
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    Development of a model of 3D imaging for the pre-operative planning of TaTME
    (Oxford University Press, 2018) Sahnan, K.; Pellino, G.; Adegbola, S.O.; Tozer, P.J.; Chandrasinghe, P.; Misovik, D.; Hompes, R.; Hart, A.L.; Warusavitarne, J.; Lung, R.F.
    BACKGROUND:Transanal TME (TaTME) is a new addition to the approaches in rectal surgery. TaTME requires advanced technical skills and, more importantly, knowledge of the pelvic structures, planes, and spaces as they are encountered moving cephalad from the perineum. We have developed a technique for producing 3D reconstructions of the anorectum and associated anatomy, to aid peri-operative planning and understanding of the anatomy crucial to TaTME surgery. METHODS: A patient was scheduled for single incision laparoscopy surgery (SILS) TaTME completion proctectomy and ileoanal pouch formation for ulcerative colitis. Standard axial T2-weighted Spectral Attenuated Inversion Recovery (SPAIR) and sagittal T2-weighted MRI sequences were obtained and digital imaging and communications in medicine (DICOM) images were imported into a validated open-source segmentation software.1 A specialist consultant gastrointestinal radiologist manually segmented the following structures: sphincter complex; rectosigmoid colon; levator plate, bladder, ureters, urethra and prostate. Each mesh was imported into another open-source system, MeshLab V1.3.3.1 as Stereolithography (STL) files for mesh smoothing to be applied. Individual labels were applied to each anatomical structure. RESULTS: Segmentation took approximately 15 min and an additional 10 min was required for smoothing and applying colour and transparency of the anatomical structures to emphasise surgically relevant anatomy. In Figure (A) provides an overview of the anatomy showing a relatively straight and posterior direction of the rectum as it descends into the pelvis; (B) provides insight into the relation between internal sphincter/rectum and the prostate/urethra. Distance between structures and relative proximity can be easily understood. Figure (C) shows the clearance between low rectum and both ureters, whilst (D) shows an anterior oblique view of the sphincter complex and the urethra. Conclusions :Surgeons currently use a combination of MRI scans, reports and discussion with radiologists to better understand anatomy. The use of these reconstructions in the MDT, in clinic and in the operating theatre could be useful to better communicate complex rectal anatomy, identify areas of difficulty and aid surgical planning. Our reconstructions present a present a cost-neutral solution to better visualise the anatomy they represent the first step towards innovation in TaTME surgery.
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    Transanal minimally invasive proctectomy (TaMIP) in patients with Crohn’s disease: A cohort study from the TaTME international database
    (Oxford University Press, 2018) Pellino, G.; Sahnan, K.; Penna, M.; Adegbola, S.; Chandrasinghe, P.; Hompes, R.; Spinelli, A.; Warusavitarne, J.; International TaTME Registry Collaborative
    BACKGROUND :Perianal Crohn’s disease (pCD) is a debilitating condition and despite the advances of medical and surgical treatment, a proportion of patients eventually require proctectomy for severe and/or refractory pCD. TaTME has several advantages, particularly in patients with low rectal cancer, narrow pelvis, previous radiation and bulky prostate. Aim of this study is to assess the feasibility of transanal minimally invasive proctectomy (TaMIP) within the International TaTME registry. METHODS:The TaTME registry was interrogated from 2014 to 2017 for benign conditions. Data were collected across 11 international centres submitted for patients who received TaMIP, with or without TME, for pCD. RESULTS:Forty patients (mean age 42.6 ± 13.8 years) underwent TaMIP for pCD with a median total operative time of 202 ± 102 min for the abdominal phase and 126 ± 58 min for the perineal phase. The majority of patients were female (67.5%; 27 of 40), 80.0% had active IBD at the time of surgery and average duration of follow-up was 4.4 ± 5.8 months. The commonest approach to proctectomy was an intersphincteric APE (30.0%; 12 of 40), with over half of cases (52.5%; 21 of 40) undergoing total intersphincteric dissection. The median height of the pursestring was 4.4 ± 2.4 cm and the most common extraction site was transanal (37.5%; 15 of 40). Intact specimens were found in 21% (8 of 38 TME) and major defects in four cases. During the abdominal phase, 29% (9 of 31) cases were converted-to-open procedure (all strategic) and 20% (8 of 40) during the perineal phase. Peri-operative complications during perineal dissection were: bleeding (12.5%, 5 of 40), incorrect plane (15%, 6 of 40), issues with smoke extraction (12.5%; 5 of 40) and maintaining pneumopelvis (10.0%; 4 of 40). Rectal perforations occurred in two cases at a median of 4 ± 2.8 cm from the anal verge. There were no urethral injuries and blood loss was < 100 ml in 45.4% (15.33) in our cohort. The average length of stay was 6 ± 5 days with no post-operative mortalities. The majority of patients (75.0%; 30 of 40) had no complications. Two-thirds of patients had Clavien-Dindo grade II complications (60.0%; 6 of 40) and one patient had a grade III complication. Late morbidity (>1 month) was available for 23 patients and perineal wound complications were identified in over half of patients (56.5%). CONCLUSIONS: pCD causes perineal fibrosis and chronic sepsis, which can make proctectomy an extremely complex operation (particularly when associated with proctitis), thereby increasing the risk of complications. TaMIP offers a safe and feasible minimally invasive approach to this subset of patients. Outcomes from TaMIP need to be compared with current techniques in order to discern the future role and training requirements for this promising new technique.
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    Transanal minimally invasive proctectomy (TaMIP) in patients with inflammatory bowel diseases (IBD) within the TaTME international database
    (Oxford University Press, 2018) Pellino, G.; Sahnan, K.; Penna, M.; Adegbola, S.; Chandrasinghe, P.; Spinelli, A.; Hompes, R.; Warusavitarne, J.; International TaTME Registry Collaborative
    BACKGROUND : The necessity of proctectomy in IBD often represents refractory disease, with severe active/chronic inflammation, frequently in the context of immunosuppression. Minimally invasive techniques are currently being used as an option in the often challenging operations required. We aim to assess the feasibility and short-term outcomes of a transanal minimally invasive approach to proctectomy (TaMIP) in patients undergoing surgery for IBD within the TaTME registry. METHODS: The TaTME registry (secure online database), was interrogated from 2014 to 2017 for benign conditions. Data were collected across 11 international centres submitted for IBD patients. Patients with ulcerative colitis (UC) received proctectomy with or without Ta-IPAA, and patients with Crohn’s disease (CD) received TaMIP, with or without total mesorectal excision (TME), for perianal CD (pCD).RESULTS: In total, 174 patients with a median BMI of 25.6 ± 4.7 kg/m2 were entered into the database. The majority of patients (77%; 134 of 174) had UC and 79.9% (111 of 174) had a simultaneous laparoscopic or single-incision laparoscopic (SILS) approach to the abdomen. Active IBD featured in 63.8% (111 of 174) which was more prominent in the CD patients (80% vs. 59%, p = 0.015) and 19% (33 of 174) were on steroids at the time of surgery. The median total operative time was 249 ± 113 min (abdominal phase 206 ± 112 and perineal phase 133 ± 60 min). An incorrect plane was the most common problem encountered intra-operatively (10.3%; 18 of 174) followed by bleeding (9.2%; 16 of 174). There was an inadvertent rectal perforation rate of 5.6% (6 of 107). Over a fifth of abdominal procedures were converted (21.6%; 30 of 139) compared with 17 (9.8%) in the perineal phase. There were more perineal conversions in CD patients (20% vs. 6.7%, p = 0.028). A purse-string was used in 51.1% (81 of 174) at a median height of 3.8 ± 2 cm. Most anastomoses were created using a stapler (85.1%; 57 of 67) at median distance of 2.9 ± 1.5 cm from the anal verge. The median length of postoperative stay was 9 ± 6.5 days, which was longer in the UC patients (9 ± 7 days vs. 6 ± 5 days, p = 0.0079). There were no mortalities. Forty-four patients (25.3%) had a complication and seven (15.9%) of these (i.e. 4% of total cohort) had a grade III Clavien-Dindo complication (re-operation). Data on late morbidity (>1 month) were available in 92 patients and 15 of these patients (16.3%) had a wound breakdown. Two of these had a VAC dressing and three had re-operations. There was a trend towards more wound sinuses in CD (19% vs. 4.8%, p = 0.062). CONCLUSIONS:Our results demonstrate that the application of a transanal minimally invasive approach to proctectomy is a feasible option in IBD patients with a relatively low complication rate.
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    Transanal minimally invasive proctectomy with ileal pouch anal anastomosis (Ta-IPAA) in patients with ulcerative colitis: a cohort study from the TaTME international database
    (Oxford University Press, 2018) Pellino, G.; Sahnan, K.; Penna, M.; Adegbola, S.; Chandrasinghe, P.C.; Spinelli, A.; Hompes, R.; Warusavitarne, J.; International TaTME Registry Collaborative
    BACKGROUND:Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) can achieve excellent outcomes in terms of function and quality of life, for patients refractory to medical therapy for ulcerative colitis (UC). Minimally invasive approaches are gaining momentum and evolution of the transanal approach to rectal surgery has led to broadening its use, from total mesenteric excision (TME) in cancer, to include IPAA in ulcerative colitis. In this study, we analysed the short-term outcomes of transanal minimally invasive IPAA (Ta-IPAA) within the International TaTME registry.METHODS:The TaTME registry, a secure online database was interrogated from 2014 to 2017 for benign conditions. Data were collected across 11 international centres submitted for patients who received Ta-IPAA, with or without TME, for UC. RESULTS:Sixty-nine patients with a median age of 38.6 ± 12.2 years were entered into the database. The majority of patients were male (75.4%; 52/69) and had a median BMI of 24.4 ± 4 kg/m2. There were no smokers in our cohort. Over half of the patients (53.6; 37/69) had active IBD at the time of surgery and 12 patients were on steroids at the time of the surgery. A proctectomy in the TME plane was the most common approach (75.4%; 52/69), a close rectal dissection was chosen in 13 patients and in four patients the plane was not specified. A simultaneous abdominal/TaTME approach was performed in over two-thirds of cases (69.6%; 48/69) and most surgeons either used an SILS approach (46.4%; 32/69) or a laparoscopic approach (40.6%; 28/69). A pursestring was used by the majority (87%; 60/69) at a median height of 4 ± 1.6 cm. The majority of pouches were created using a stapler (85.1%; 57/69) at a median distance of 2.9 ± 1.5 cm from the anal verge. Median operative time was 311 ± 126 min. Under a quarter of abdominal operations were converted (24.6%; 14/57) compared with four cases (5.8%) in the perineal phase. The median length of postoperative stay was 10 ± 6 days and three patients had a re-operation. There were no mortalities. Three patients (4.3%) had an anastomotic leak and two patients (2.9%) had collections. Late morbidity (>1 month) was available in 31 patients and of these seven patients (22.6%) had a stricture. CONCLUSIONS: Transanal minimally invasive proctectomy with ileal pouch anal anastomosis is feasible and safe in patients with UC. It is also associated with relatively low rates of re-operation and anastomotic leakage.
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    Single Incision Laparoscopic Surgery (SILS) as surgical option in Crohn's disease: our experience
    (Oxford University Press, 2018) Leo, C.A.; Samaranayake, S.F.; Hodgkinson, J.D.; Santorelli, C.; Chandrasinghe, P.C.; Warusavitarne, J.
    BACKGROUND:Transanal TME (TaTME) is a new addition to the approaches in rectal surgery. TaTME requires advanced technical skills and, more importantly, knowledge of the pelvic structures, planes, and spaces as they are encountered moving cephalad from the perineum. We have developed a technique for producing 3D reconstructions of the anorectum and associated anatomy, to aid peri-operative planning and understanding of the anatomy crucial to TaTME surgery. METHODS: A patient was scheduled for single incision laparoscopy surgery (SILS) TaTME completion proctectomy and ileoanal pouch formation for ulcerative colitis. Standard axial T2-weighted Spectral Attenuated Inversion Recovery (SPAIR) and sagittal T2-weighted MRI sequences were obtained and digital imaging and communications in medicine (DICOM) images were imported into a validated open-source segmentation software.1 A specialist consultant gastrointestinal radiologist manually segmented the following structures: sphincter complex; rectosigmoid colon; levator plate, bladder, ureters, urethra and prostate. Each mesh was imported into another open-source system, MeshLab V1.3.3.1 as Stereolithography (STL) files for mesh smoothing to be applied. Individual labels were applied to each anatomical structure. RESULTS: Segmentation took approximately 15 min and an additional 10 min was required for smoothing and applying colour and transparency of the anatomical structures to emphasise surgically relevant anatomy. In Figure (A) provides an overview of the anatomy showing a relatively straight and posterior direction of the rectum as it descends into the pelvis; (B) provides insight into the relation between internal sphincter/rectum and the prostate/urethra. Distance between structures and relative proximity can be easily understood. Figure (C) shows the clearance between low rectum and both ureters, whilst (D) shows an anterior oblique view of the sphincter complex and the urethra. Conclusions :Surgeons currently use a combination of MRI scans, reports and discussion with radiologists to better understand anatomy. The use of these reconstructions in the MDT, in clinic and in the operating theatre could be useful to better communicate complex rectal anatomy, identify areas of difficulty and aid surgical planning. Our reconstructions present a present a cost-neutral solution to better visualise the anatomy they represent the first step towards innovation in TaTME surgery.
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    Long-term function after transanal vs. transabdominal ileal pouch-anal anastomosis for ulcerative colitis: a multi-centre cohort study
    (Oxford University Press, 2019) Chandrasinghe, P.; Carvello, M.; Wasmann, K.; Tanis, P.; Warusavitarne, J.; Spinelli, A.; Bemelman, W.
    BACKGROUND:The transanal approach has been introduced in ileal pouch-anal (IPAA) surgery to gain better exposure for the rectal dissection. It has been shown to be safe with lower morbidity than the trans-abdominal approach. The aim of this study was to compare functional outcome of transanal ileal pouch-anal anastomosis (ta-IPAA) with transabdominal (abd-IPAA) approach for ulcerative colitis (UC) using the Cleveland Global Quality of Life (CGQL). METHODS: This is a multi-centre cohort of consecutive patients undergoing abd-IPAA or ta-IPAA for UC prospectively registered in the databases of three tertiary referral institutions between March 2002 to September 2017. Patient characteristics, surgical details and postoperative outcomes were retrieved. The primary end-point was pouch function determined by CGQL score. The questionnaire was administered to all patients with a functioning pouch for 12 months. RESULTS: Ninety-nine patients with ta-IPAA were compared with 274 patients with abd-IPAA. A defunctioning stoma was created at the time of pouch construction in 46 (46%) patients undergoing ta-IPAA and in 130 (47%) patients with abd-IPAA (p = 0.90). Thirty-day postoperative complications according to Clavien-Dindo classification (p = 0.22) as well as anastomotic leak rates (13% vs. 6%), abd-IPAA and ta-IPAA, respectively, were comparable (p = 0.09). Time to stoma closure did not differ between the two groups (abd-IPAA- 6 ± 7 vs. ta-IPAA- 5 ± 4 months; p = 0.72). Twelve months CGQL score was obtained for 251 patients in the abd-IPAA group and for 97 in ta-IPAA cohort. The CGQL index was comparable between the two groups (0.72 ± 0.15 vs. 0.75 ± 0.12; p = 0.07). Quality of health and energy level components were statistically higher for ta-IPAA (7.30 ± 1.53 vs. 7.73 ± 1.19, p = 0.01; 6.68 ± 1.74 vs. 7.17 ± 1.54, p = 0.01) while no difference was found for quality of life item (7.63 ± 1.52 vs. 7.62 ± 1.30, p = 0.73). Pouch failure (including defunction and excision) was reported in 40 of 298 (12%) patients undergoing abd-IPAA and in 1 patient (1%) having ta-IPAA during the follow-up period. CONCLUSIONS: ta-IPAA produces functional result comparable to transabdominal approach at 12 months after surgery.
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    SMAD7 shows a biphasic expression pattern during progression of ulcerative colitis-associated colorectal cancer
    (Oxford University Press, 2019) Chandrasinghe, P.; Cereser, B.; Moorghen, M.; Spaggiari, P.; Maroli, A.; Del Bel Belluz, L.; Hart, A.; Spinelli, A.; Stebbing, J.; Warusavitarne, J.
    BACKGROUND: Ulcerative colitis (UC) is an idiopathic inflammation of the intestine with an increased risk of developing colitis-associated cancer (CAC). Currently, clinical trials are underway aiming to inhibit SMAD7 to ameliorate inflammation. While the direct effect of depleting SMAD7, an inhibitory molecule in the transforming growth factor-β1 (TGFβ1) pathway, may be therapeutic in UC, its indirect effect on CAC development is largely unknown. TGFβ1 is known to enhance late stages of sporadic colorectal cancers (CRC), where SMAD7 is also elevated. Therefore, we hypothesise that removing inhibition of this pathway by depleting SMAD7 may also be detrimental for CAC. We therefore evaluated the expression of SMAD7 in the colonic epithelium during the inflammation associated neoplastic process to determine a possible role of SMAD7 in CAC. METHODS: The expression of SMAD7 protein and mRNA in colonic epithelia was assessed by immunohistochemistry (IHC) and in situ hybridisation (ISH),, respectively, in a cohort of 53 archival colon samples (17 CAC, 12 dysplastic, 12 inflammed, 12 non-neoplastic/non-inflammed) from patients who have undergone colectomies for UC and CAC. The expression within the epithelial cells was evaluated by both digital quantification and validated by blind scoring by a pathologist. Significant differences were tested with one-way ANOVA and Mann–Whitney U test. RESULTS: Cytoplasmic expression of SMAD7 protein is significantly higher in the inflammed epithelium compared with non-inflamed epithelium (p < 0.0001). Interestingly, a significant decrease of the same was detected in dysplasia (p = 0.01), although this group is characterised by a higher variability. SMAD7 levels are elevated in cancer compared with dysplasia, suggesting a biphasic expression (p = 0.009), which could be in part due to the different genetic composition. SMAD7 mRNA expression was not significantly different across different stages of CAC (p = 0.49). We hypothesise that the lack of correlation between mRNA and protein levels could be attributed to yet unknown post-transcriptional or post-translational regulations. CONCLUSIONS:In our cohort of UC affected colon tissues, SMAD7 demonstrated a biphasic expression pattern along the different stages of CAC with peaks during active inflammation and cancer. The increase in SMAD7 expression during neoplastic transformation, comparable to sporadic CRC, may be a protective response of the epithelium to inhibit the effect of TGFβ1. Although inhibiting SMAD7 as a therapy for UC may remit inflammation, we hypothesise it may exacerbate CAC due to further enhancement in TGFβ1 signalling. We envisage further mechanistic studies in vitro, in particular in organoids, could help in understanding the TGFβ superfamily pathway in CAC.