- Email: [email protected]
OC.09.1 Y-SHAPED BILATERAL SELF EXPANDABLE METALLIC STENT PLACEMENT FOR MALIGNANT HILAR BILIARY OBSTRUCTION: DATA FROM A LARGE SERIES OF PATIENTS TREATED WITH THE STENT-IN-STENT TECHNIQUE
S22
Abstracts of the 20th National Congress of Digestive Diseases / Digestive and Liver Disease 46S (2014) S1–S144
OC.09.1 Y-SHAPED BILATERAL SELF EXPANDABLE METALLIC STENT PLACEMENT FOR MALIGNANT HILAR BILIARY OBSTRUCTION: DATA FROM A LARGE SERIES OF PATIENTS TREATED WITH THE STENT-IN-STENT TECHNIQUE R. Di Mitri ∗ , F. Mocciaro, S. Sferrazza Gastroenterology and Endoscopy Unit, ARNAS Civico-Di Cristina-Benfratelli Hospital, Palermo, Italy Background and aim: Malignant hilar strictures (MHS) are a clinical challenge. Self expandable metallic stents (SEMS) have proven more effective than plastic stents for palliation of MHS registering a high success rate. We report data from a large series of patients treated with the “stent-in-stent” technique. Material and methods: From Apr. 2009 to Nov. 2013 we prospectively treated 22 consecutive patients with unrespectable MHS performing endoscopic bilateral stent-in-stent deployment (Niti-S Biliary Y stent; TaeWoong, Seoul, Korea). The first uncovered SEMS, with a central wide-open mesh, was placed across the hilar stricture (if needed balloon dilation was performed), afterwards the guidewire was withdrawn slowly and was inserted under fluoroscopic guidance into the central wide-open mesh identified by radiopaque markers. The second uncovered SEMS was so placed through the central crossed mesh of the primary stent (Y-shaped configuration). Results: Ten male and 12 female were treated (mean age 64.9±15.7 years): 10 had a cholangiocarcinoma (46%), 6 a metastatic colon cancer (27%), 4 a metastatic pancreatic cancer (18%), 2 a hepatocarcinoma (9%). The types of MHS according to the Bismuth classification were II in 5 patients (23%), IIIa in 1 (4%), and IV in 16 (73%). The mean bilirubin level was 15.1±4.8 mg/dL. Technical success (outflow of contrast medium and/or bile through the stents) was achieved in all patients with a significant reduction in bilirubin levels (2.9±1.8 mg/dL); 54% [12/22] patients were treated with balloon dilation before stent placement. One patient experienced cholangitis as early complication (<30 days) while in 2, at 3 and 10 months respectively, SEMS ingrowth was observed (occlusion were managed with the insertion of a plastic stent or a new SEMS through the occluded stent). No SEMS migration or other complications were recorded. At the end of the follow-up (mean 7.4±3.3 months) 15 out of 22 patients (68%) died. Conclusions: Our experience confirms as endoscopic bilateral SEMS placement with stent-in-stent technique (Y-shaped configuration) is a feasible, effective, and safe procedure for palliation of unresectable MHS.
OC.09.2 ASPIRIN REDUCED CELL VIABILITY AND MTOR SIGNALLING IN NEUROENDOCRINE TUMOR CELL LINES M.P. Spampatti ∗,1 , G. Vlotides 2 , G. Spoettl 2 , J. Maurer 2 , B. Goeke 2 , D. Conte 1 , C.J. Auernhammer 2 1 Università degli Studi di Milano, Milano, Italy; 2 Medizinische Klinik 2, Klinikum LMU, Munich, Germany
Background and aim: Acetylsalicylic acid (i.e. aspirin), has been demonstrated to have antitumor activity in several cancer cell lines. At present, no preclinical data are available concerning the effect of aspirin on NETs. Therefore, this in vitro study was aimed at investigating the possible effect of aspirin on NET cell growth. Material and methods: The effect of aspirin was evaluated on both pancreatic neuroendocrine cells BON1 and bronchopulmonary neuroendocrine cells NCI-H727. BON1 and NCI-H727 cells were treated with increasing concentrations of aspirin (from 0,001 to 5mM) and the effects on metabolic activity and cell proliferation were measured with Cell Titer 96 Aqueous One Solution cell proliferation assay (Promega, Madison, USA) and SYBR-DNAlabeling after 72, 144 and 216 hours of incubation. The effects of aspirin were determined with Western blot. Results: Treatment with aspirin time- and dose-dependently suppressed BON1 and NCI-H727 cell viability and proliferation. For both cell lines, these effects were statistically significant starting from a dose of 0.5-1 mM, and peaked at 5 mM. For instance, treatment with aspirin 1 mM for 144 hrs, decreased
cell viability to 66±13% (p<0.05 vs no treatment) for BON1 and to 53±8% (p<0.01 vs no treatment) for NCI-H727 cells. Similar data were reported by SYBR-DNA labelling experiments. Again, aspirin suppressed mTOR downstream signalling, as evidenced by reduced phosphorylation of mTOR substrates, i.e. 4E binding protein 1 (4EBP1), serine/threonine kinase P70S6K and S6 ribosomal protein. A compensatory activation of the serine/threonine specific protein kinase AKT and of extracellular signal-regulated kinases (ERK) was also observed. However, these findings were not related to an increased upstream growth factor signalling, as aspirin suppressed phosphorylation of epidermal growth factor receptor (EGFR) and of proto-oncogene c-MET. Conclusions: Present preliminary results, obtained in vitro, suggest a promising anticancer activity of aspirin on NETs. Further ad hoc designed preclinical and clinical studies are mandatory.
OC.09.3 ANALYSIS OF CLINICAL AND ENDOSCOPIC FACTORS PREDISPOSING THE SUCCESS OF ERCP IN RESOLUTION OF BILIARY ANASTOMOTIC STRICTURES AFTER LIVER TRANSPLANTATION S.F. Vadalà Di Prampero ∗ , M. Bulajic, L.M. Zoratti, P. Rossitti, J. Panos, I. Lodolo, E. Pinese, M. Zilli Gastroenterology Unit, University Hospital of Udine, Udine, Italy Background and aim: The main biliary complication following liver transplantation (LT) is biliary anastomotic stricture (BAS). To define possible predisposing factors of BAS appearance and resolution we analyzed different epidemiological, clinical and endoscopic features in patients undergoing ERCP. Material and methods: We evaluated 171 consecutive liver transplanted recipients recruited in our Centre from 2004 to 2010 (133 males, median age 56 years), with at least one year of follow-up. All patients with clinical or radiologic suspicion of obstructive jaundice and cholestasis underwent ERCP. The concept of ERCP was based on biliary sphyncterotomy followed by stricture dilation and placement of at least one plastic stent, exchangeable every 3-6 months until the final stricture resolution. Results: During post-operative follow-up 40 patients presented BAS. The median number of ERCP per patient was 3, median number of stents inserted per patient per procedure was 1 and median period until stricture resolution was 9 months. Stricture resolution was obtained in 83%. Occurrence of BAS was strongly associated with use of Kehr T tube (12/23 Vs 28/148, p<0.01) and with use of cyclosporine as immunosuppressive therapy (18/54 Vs 22/117, p<0.05). The univariate logistic analysis showed that elevated number of repeated ERCP (OR 0,659; 95% CI: 0.522–0.832; p=0.000), combined stenting with dilation (OR 0,197; 95% CI: 0.074–0.525; p=0.001), increasing number of inserted stents per procedure (OR 0.896; 95% CI: 0.782–1.026; p=0.112) and longer period of warm ischemia (OR 0.966; 95% CI: 0.938– 0.995; p=0.023) were associated with successful endoscopic treatment. On the contrary, longer period of stent in place (OR 1.034; 95% CI: 1.005–1.064; p=0.021), elevated MELD score (OR 1.104; 95% CI: 1.035–1.178; p=0.003), elevated Child-Pugh score (OR 1.679; 95% CI: 1.089–2.591; p=0.019) and high pre-transplantation bilirubin values (OR 1.104; 95% CI: 1.007–1.210; p=0.035) were associated with endoscopic treatment failure. Conclusions: Understanding clinical and endoscopic risk factors may help in predicting of more appropriate regimen of treatment of patients undergoing ERCP for BAS post-LT.
Abstracts of the 20th National Congress of Digestive Diseases / Digestive and Liver Disease 46S (2014) S1–S144
OC.09.1 Y-SHAPED BILATERAL SELF EXPANDABLE METALLIC STENT PLACEMENT FOR MALIGNANT HILAR BILIARY OBSTRUCTION: DATA FROM A LARGE SERIES OF PATIENTS TREATED WITH THE STENT-IN-STENT TECHNIQUE R. Di Mitri ∗ , F. Mocciaro, S. Sferrazza Gastroenterology and Endoscopy Unit, ARNAS Civico-Di Cristina-Benfratelli Hospital, Palermo, Italy Background and aim: Malignant hilar strictures (MHS) are a clinical challenge. Self expandable metallic stents (SEMS) have proven more effective than plastic stents for palliation of MHS registering a high success rate. We report data from a large series of patients treated with the “stent-in-stent” technique. Material and methods: From Apr. 2009 to Nov. 2013 we prospectively treated 22 consecutive patients with unrespectable MHS performing endoscopic bilateral stent-in-stent deployment (Niti-S Biliary Y stent; TaeWoong, Seoul, Korea). The first uncovered SEMS, with a central wide-open mesh, was placed across the hilar stricture (if needed balloon dilation was performed), afterwards the guidewire was withdrawn slowly and was inserted under fluoroscopic guidance into the central wide-open mesh identified by radiopaque markers. The second uncovered SEMS was so placed through the central crossed mesh of the primary stent (Y-shaped configuration). Results: Ten male and 12 female were treated (mean age 64.9±15.7 years): 10 had a cholangiocarcinoma (46%), 6 a metastatic colon cancer (27%), 4 a metastatic pancreatic cancer (18%), 2 a hepatocarcinoma (9%). The types of MHS according to the Bismuth classification were II in 5 patients (23%), IIIa in 1 (4%), and IV in 16 (73%). The mean bilirubin level was 15.1±4.8 mg/dL. Technical success (outflow of contrast medium and/or bile through the stents) was achieved in all patients with a significant reduction in bilirubin levels (2.9±1.8 mg/dL); 54% [12/22] patients were treated with balloon dilation before stent placement. One patient experienced cholangitis as early complication (<30 days) while in 2, at 3 and 10 months respectively, SEMS ingrowth was observed (occlusion were managed with the insertion of a plastic stent or a new SEMS through the occluded stent). No SEMS migration or other complications were recorded. At the end of the follow-up (mean 7.4±3.3 months) 15 out of 22 patients (68%) died. Conclusions: Our experience confirms as endoscopic bilateral SEMS placement with stent-in-stent technique (Y-shaped configuration) is a feasible, effective, and safe procedure for palliation of unresectable MHS.
OC.09.2 ASPIRIN REDUCED CELL VIABILITY AND MTOR SIGNALLING IN NEUROENDOCRINE TUMOR CELL LINES M.P. Spampatti ∗,1 , G. Vlotides 2 , G. Spoettl 2 , J. Maurer 2 , B. Goeke 2 , D. Conte 1 , C.J. Auernhammer 2 1 Università degli Studi di Milano, Milano, Italy; 2 Medizinische Klinik 2, Klinikum LMU, Munich, Germany
Background and aim: Acetylsalicylic acid (i.e. aspirin), has been demonstrated to have antitumor activity in several cancer cell lines. At present, no preclinical data are available concerning the effect of aspirin on NETs. Therefore, this in vitro study was aimed at investigating the possible effect of aspirin on NET cell growth. Material and methods: The effect of aspirin was evaluated on both pancreatic neuroendocrine cells BON1 and bronchopulmonary neuroendocrine cells NCI-H727. BON1 and NCI-H727 cells were treated with increasing concentrations of aspirin (from 0,001 to 5mM) and the effects on metabolic activity and cell proliferation were measured with Cell Titer 96 Aqueous One Solution cell proliferation assay (Promega, Madison, USA) and SYBR-DNAlabeling after 72, 144 and 216 hours of incubation. The effects of aspirin were determined with Western blot. Results: Treatment with aspirin time- and dose-dependently suppressed BON1 and NCI-H727 cell viability and proliferation. For both cell lines, these effects were statistically significant starting from a dose of 0.5-1 mM, and peaked at 5 mM. For instance, treatment with aspirin 1 mM for 144 hrs, decreased
cell viability to 66±13% (p<0.05 vs no treatment) for BON1 and to 53±8% (p<0.01 vs no treatment) for NCI-H727 cells. Similar data were reported by SYBR-DNA labelling experiments. Again, aspirin suppressed mTOR downstream signalling, as evidenced by reduced phosphorylation of mTOR substrates, i.e. 4E binding protein 1 (4EBP1), serine/threonine kinase P70S6K and S6 ribosomal protein. A compensatory activation of the serine/threonine specific protein kinase AKT and of extracellular signal-regulated kinases (ERK) was also observed. However, these findings were not related to an increased upstream growth factor signalling, as aspirin suppressed phosphorylation of epidermal growth factor receptor (EGFR) and of proto-oncogene c-MET. Conclusions: Present preliminary results, obtained in vitro, suggest a promising anticancer activity of aspirin on NETs. Further ad hoc designed preclinical and clinical studies are mandatory.
OC.09.3 ANALYSIS OF CLINICAL AND ENDOSCOPIC FACTORS PREDISPOSING THE SUCCESS OF ERCP IN RESOLUTION OF BILIARY ANASTOMOTIC STRICTURES AFTER LIVER TRANSPLANTATION S.F. Vadalà Di Prampero ∗ , M. Bulajic, L.M. Zoratti, P. Rossitti, J. Panos, I. Lodolo, E. Pinese, M. Zilli Gastroenterology Unit, University Hospital of Udine, Udine, Italy Background and aim: The main biliary complication following liver transplantation (LT) is biliary anastomotic stricture (BAS). To define possible predisposing factors of BAS appearance and resolution we analyzed different epidemiological, clinical and endoscopic features in patients undergoing ERCP. Material and methods: We evaluated 171 consecutive liver transplanted recipients recruited in our Centre from 2004 to 2010 (133 males, median age 56 years), with at least one year of follow-up. All patients with clinical or radiologic suspicion of obstructive jaundice and cholestasis underwent ERCP. The concept of ERCP was based on biliary sphyncterotomy followed by stricture dilation and placement of at least one plastic stent, exchangeable every 3-6 months until the final stricture resolution. Results: During post-operative follow-up 40 patients presented BAS. The median number of ERCP per patient was 3, median number of stents inserted per patient per procedure was 1 and median period until stricture resolution was 9 months. Stricture resolution was obtained in 83%. Occurrence of BAS was strongly associated with use of Kehr T tube (12/23 Vs 28/148, p<0.01) and with use of cyclosporine as immunosuppressive therapy (18/54 Vs 22/117, p<0.05). The univariate logistic analysis showed that elevated number of repeated ERCP (OR 0,659; 95% CI: 0.522–0.832; p=0.000), combined stenting with dilation (OR 0,197; 95% CI: 0.074–0.525; p=0.001), increasing number of inserted stents per procedure (OR 0.896; 95% CI: 0.782–1.026; p=0.112) and longer period of warm ischemia (OR 0.966; 95% CI: 0.938– 0.995; p=0.023) were associated with successful endoscopic treatment. On the contrary, longer period of stent in place (OR 1.034; 95% CI: 1.005–1.064; p=0.021), elevated MELD score (OR 1.104; 95% CI: 1.035–1.178; p=0.003), elevated Child-Pugh score (OR 1.679; 95% CI: 1.089–2.591; p=0.019) and high pre-transplantation bilirubin values (OR 1.104; 95% CI: 1.007–1.210; p=0.035) were associated with endoscopic treatment failure. Conclusions: Understanding clinical and endoscopic risk factors may help in predicting of more appropriate regimen of treatment of patients undergoing ERCP for BAS post-LT.