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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Author: search.filters.author.Chandrasinghe, P.Subject: search.filters.subject.Colitis, Ulcerative

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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.
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    Long-term function after transanal versus transabdominal ileal pouch-anal anastomosis for ulcerative colitis: a multicenter cohort study
    (Wiely-Blackwell, 2019) Chandrasinghe, P.; Carvello, M.; Wasmann, K.; Tanis, P.; Warusavitarne, J.; Spinelli, A.; Bemelman, W.
    AIM:The novel transanal approach to ileal pouch-anal anastomosis (ta-IPAA) provides better exposure with lower short-term morbidity in ulcerative colitis (UC). The aim of this study was to assess the long-term outcomes after ta-IPAA versus abdominal IPAA (abd-IPAA) in UC. METHOD:This is a multicentre cohort analysis between March 2002 and September 2017. Patient characteristics, surgical details and postoperative outcomes were compared. The primary end-point was CGQL (Cleveland Global Quality of Life) score at 12 months. RESULTS:374 patients (100 ta-IPAA vs 274 abd-IPAA) were included. Mean CGQL scores were comparable between the two groups (0.75 ± 0.11 vs 0.71 ± 0.14; respectively, P = 0.1). Quality of life (7.71 ± 1.17 vs 7.30 ± 1.46; P = 0.04) and energy level (7.16 ± 1.52 vs 6.66 ± 1.68; P = 0.03) were significantly better after ta-IPAA, while the quality of health item was comparable (7.68 ± 1.26 vs 7.64 ± 1.44; P = 0.9655). Stool frequencies (> 10/24 h:22% vs 21%; P = 1.0) and major incontinence rates (27% vs 26%; P = 0.89) were similar. Thirty-day morbidity rates (33% vs 41%; P = 0.2) and anastomotic leak rates were comparable (6% vs 13%; P = 0.09). CONCLUSION: This study, for the first time, provides evidence of comparable long-term functional outcome of ta-IPAA vs abd-IPAA for UC.