Mo1430 Nitroglycerine for Prevention of Post-ERCP Pancreatitis: Meta-Analysis of Randomized...

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Mo1430 Nitroglycerine for Prevention of Post-ERCP Pancreatitis: Meta- Analysis of Randomized Controlled Trials Priyanka Tiwari, Abdul S. Khan, Jonathan P. Nass, Ricardo V. Romero, Mainor R. Antillon, Ramon E. Rivera, Praveen K. Roy Ochsner Clinic Foundation, New Orleans, LA Background and Aims: Acute pancreatitis is a common complication of ERCP. Over the years, attempts have been made to identify an agent to prevent this complication. Several recent studies have evaluated the efficacy of nitroglycerine (NTG) with mixed results. We conducted a meta-analysis of randomized controlled trials to evaluate the efficacy and safety of nitroglycerine for prevention of post-ERCP pancreatitis. Methods: MEDLINE, Cochrane Central Register of Controlled Trials & Database of Systematic Reviews, PubMed, and recent abstracts from major conference proceedings were searched (through 11/ 10). RCTs comparing nitroglycerine to placebo for prevention of post-ERCP pancreatitis were included. Standard forms were used to extract data by two independent reviewers. The effects of nitroglycerine were analyzed by calculating pooled estimates of post-ERCP pancreatitis. Pooled odds ratio (OR) was calculated using Comprehensive Meta-analysis software. The number needed to treat (NNT) was also calculated. Publication bias was assessed by funnel plots. All studies were graded by Jadad score. Heterogeneity among studies was assessed. Results: Nine RCTs (N2,020) met the inclusion criteria. Nitroglycerine was administered transdermally (4 trials), sublingually (2 trials), topically at the ampulla (2 trials) and intravenously (1 trial). The dose and timing of administration of nitroglycerine varied among the studies. Overall pooling of the studies showed that nitroglycerine decreased the odds of post-ERCP pancreatitis (OR 0.64, 95% CI: 0.45 - 0.92, p 0.01). The relative risk reduction was 23% (95% CI: 9-52%). The NNT was 50. Sub-group analysis revealed that the sublingual route of administration was the most efficacious route (OR 0.34, 95% CI: 0.16-0.75, p0.007, NNT 8). No statistical difference was seen between the studies that used a higher dose (5mg/hr) or a lower dose ( 5mg/hr). No difference in the outcomes was noted based on the time of administration ( or 30 mins before ERCP). Significant reduction in post- ERCP pancreatitis was seen in studies with high rates of pancreatitis in the placebo arm. This suggests that NTG may be useful in high-risk situations (high risk patients or low volume centers). No significant heterogeneity was present. Headache and transient hypotension were the most common complications encountered. Conclusions: Nitroglycerine decreases the odds of post-ERCP pancreatitis, with high risk patients likely to benefit the most from its administration. Although our subgroup analysis suggests that the sublingual route as the most efficacious route (NNT 8), the optimal route, timing and dosing warrant further studies. Mo1431 The Use of Additional Sampling Methods and Molecular Markers in the Diagnosis of Cytology Negative Biliary Strictures Tamas A. Gonda, Michael P. Glick, Amrita Sethi, John M. Poneros, Susana Gonzalez, Peter D. Stevens Division of Digestive and Liver Diseases, Columbia UNiversity Medical Center, New York, NY INTRODUCTION. Biliary stenoses that are not associated with a mass, metastasis or recent stone disease and bile duct trauma remain difficult to diagnose by ERCP. These strictures are often concerning for a malignancy and an accurate diagnosis is critical for further planning of therapy. Although brush cytology, the mainstay of diagnosis, has a very high specificity, the sensitivity is very low. The goal of our study was to evaluate the additional yield of targeted sampling methods and molecular markers in the diagnosis of bile duct cancer. METHODS. We conducted a retrospective review of all indeterminate biliary strictures evaluated at our institution over a three year period and identified those with a final diagnosis of malignancy. A cytology result was considered positive when it was read as “malignant” or “suspicious” by a cytopathologist. In false negative cytology cases we identified all patients who underwent biliary biopsy, cholangioscopic targeted biopsies, biliary aspiration and EUS/FNA as well as FISH. FISH was performed using CEP3, 7 and 17 probes for chromosome enumeration and 9p21 for deletion and we evaluated the performance of both polysomy alone and polysomy combined with the presence of 9p21 deletion. RESULTS. There were 124 biliary strictures and 42 of them were later diagnosed as malignant. Initial cytology was positive in 14 (sensitivity of cytology was 33%). The sensitivity of the additional diagnostic modalities is described in the Table. Among the 28 patients with, false negative cytology direct biopsy was performed in 14, cholangioscopic biopsy in 9, biliary aspiration in 9 and EUS FNA in 17. FISH was performed in all cases and was interpretable in 26. The yield of these tests in cases when cytology was negative is shown below. Among all cases that were negative by cytology, FISH polysomy or 9p21 deletion was the single diagnostic modality in 15/28 cases. Among the 10 false negative cases by both cytology and FISH, one was diagnosed by cholangioscopic biopsy and two by EUS/FNA. CONCLUSIONS. These data suggest that FISH should always be included in the diagnosis of indeterminate strictures as this method offers higher sensitivity and yield then any other sampling modality. In relatively rare instances targeted biopsy may yield diagnosis when FISH or cytology does not. Sensitivity and yield of molecular markers and additional sampling methods in the diagnosis of biliary malignancy Sensitivity Yield in False Negative (FN) cases by cytology (n28) Yield in FN cases by cytology and FISH (n10) Biopsy 35 1/9 (11%) 0/4 Cholangioscopic Biopsy 44 3/7 (42%) 1/3 Aspirate 0 0/8 (0%) 0/4 EUS FNA 29 2/10 (20%) 2/5 FISH polysomy 55 12/26 (46 %) FISH polysomy/9p21 deletion 73 17/26 (65%) Mo1432 Self Expandable Metal Stents for Anastomotic Stricture Following Liver Transplant: Should We Go Back to Plastic Stenting? Jorge Cerecedo-Rodriguez, Melissa S. Phillips, Paola Figueroa-Barojas, Monica Gaidhane, Timothy M. Schmitt, Sean C. Kumer, Michel Kahaleh Digestive Health, University of Virginia, Charlottesville, VA Background: Biliary complications are frequent after liver transplantation (LT), with an incidence range of 7-51%. Endoscopic treatment with plastic stent placement has been preferred since it is a less invasive alternative to surgical management. The use of self-expandable metal stents (SEMS) has been reported in post-LT strictures. The aim of this study was to compare the success rates of three types of covered self- expandable metal stents (CSEMS) for the treatment of post-LT strictures. Methods: Data from patients who had undergone LT with biliary strictures were retrieved from a prospectively established database. Patients receiving covered metal stent were divided into three groups. Group A received partially CSEMS (Wallstent, Boston Scientific), Group B received fully CSEMS with fins (Viabil, Conmed), and Group C received fully CSEMS with flared ends (Wallflex, Boston Scientific). Technical success, stricture resolution, number of ERCP procedures, follow up, immediate and late complications were recorded. Results: A total of 55 patients were included. There were 19 patients in Group A (14 male, mean age 5210.83 [range 29-70]), 21 patients in Group B (14 male, mean age 557.43 [range 43-70]) and 15 patients in Group C (12 male, mean age 58.536.68 [range 46-71]). The indications for transplantation included Hepatitis C virus (A7, B9, C4), alcoholic liver disease (A3, B2, C5) and other diagnosis (A9, B10, C6). There were no statistically significant differences between groups with regards to demographics. The CSEMS were successfully deployed in all 55 cases. The was no evidence of significant difference with regards to stricture resolution (14 [73.68%] vs. 15 [71.42%] vs. 9 [75%] p0.6630, df2) or complications between groups. There was 1 post- ERCP pancreatitis in group B. Stent-related complications were as follows: 3 in group A (2 proximal stent migrations and 1 stent occlusion), 5 in group B (4 stent occlusions and 1 proximal migration), and 1 proximal migration in group C (p0.3894, df2). There were no complications reported during the removal of the stents. A total of 3 cases required surgery (hepatico-jejunostomy) due to refractory strictures. One non-procedure-related death was reported in Group C. Conclusions: Global success rate of CSEMS (70.37%) proved to be unsatisfactory. There were no significant differences between stent types. Occlusion and migration were the main failure causes. These results need to be confirmed in a randomized multicenter trial. Table 1. Patient characteristics (n55) Group A Group B Group C p-value WALLSTENT Gore Viabil WALLFLEX Number of patients 19 21 15 Age y, mean (range) 52.3110.83 (29-70) 55.427.43 (43-70) 58.536.68 (46-71) 0.12 Male/Female 14/5 14/7 12/3 0.679 (df2) Indication for transplantation HCV 7 9 4 ETOH 3 2 5 0.465 (df4) Other 9 10 6 Days to Stent removal 130.7295.73 (24-393) 12569.21 (17-266) 136.91105.62 (22-401) 0.925 ERCPs previous to CSEMS 2.62.1 (0-7) 0.621.12 (0-4) 1.21.89 (0-7) 0.002 Total ERCPs 6.794.59 (2-18) 3.481.75 (2-8) 2.931.71 (1-8) 0.001 Follow up after removal (mo) 38.9422.31 (1-78) 24.279.50 (5-40) 4.623.37 (0.03-11) 0.001 Abstracts www.giejournal.org Volume 73, No. 4S : 2011 GASTROINTESTINAL ENDOSCOPY AB343

Transcript of Mo1430 Nitroglycerine for Prevention of Post-ERCP Pancreatitis: Meta-Analysis of Randomized...

Mo1430Nitroglycerine for Prevention of Post-ERCP Pancreatitis: Meta-Analysis of Randomized Controlled TrialsPriyanka Tiwari, Abdul S. Khan, Jonathan P. Nass, Ricardo V. Romero,Mainor R. Antillon, Ramon E. Rivera, Praveen K. RoyOchsner Clinic Foundation, New Orleans, LABackground and Aims: Acute pancreatitis is a common complication of ERCP.Over the years, attempts have been made to identify an agent to prevent thiscomplication. Several recent studies have evaluated the efficacy of nitroglycerine(NTG) with mixed results. We conducted a meta-analysis of randomizedcontrolled trials to evaluate the efficacy and safety of nitroglycerine forprevention of post-ERCP pancreatitis. Methods: MEDLINE, Cochrane CentralRegister of Controlled Trials & Database of Systematic Reviews, PubMed, andrecent abstracts from major conference proceedings were searched (through 11/10). RCTs comparing nitroglycerine to placebo for prevention of post-ERCPpancreatitis were included. Standard forms were used to extract data by twoindependent reviewers. The effects of nitroglycerine were analyzed bycalculating pooled estimates of post-ERCP pancreatitis. Pooled odds ratio (OR)was calculated using Comprehensive Meta-analysis software. The numberneeded to treat (NNT) was also calculated. Publication bias was assessed byfunnel plots. All studies were graded by Jadad score. Heterogeneity amongstudies was assessed. Results: Nine RCTs (N�2,020) met the inclusion criteria.Nitroglycerine was administered transdermally (4 trials), sublingually (2 trials),topically at the ampulla (2 trials) and intravenously (1 trial). The dose and timingof administration of nitroglycerine varied among the studies. Overall pooling ofthe studies showed that nitroglycerine decreased the odds of post-ERCPpancreatitis (OR 0.64, 95% CI: 0.45 - 0.92, p � 0.01). The relative risk reductionwas 23% (95% CI: 9-52%). The NNT was 50. Sub-group analysis revealed that thesublingual route of administration was the most efficacious route (OR 0.34, 95%CI: 0.16-0.75, p�0.007, NNT� 8). No statistical difference was seen between thestudies that used a higher dose (�5mg/hr) or a lower dose ( � 5mg/hr). Nodifference in the outcomes was noted based on the time of administration (�or� 30 mins before ERCP). Significant reduction in post- ERCP pancreatitis wasseen in studies with high rates of pancreatitis in the placebo arm. This suggeststhat NTG may be useful in high-risk situations (high risk patients or low volumecenters). No significant heterogeneity was present. Headache and transienthypotension were the most common complications encountered. Conclusions:Nitroglycerine decreases the odds of post-ERCP pancreatitis, with high riskpatients likely to benefit the most from its administration. Although our subgroupanalysis suggests that the sublingual route as the most efficacious route (NNT 8),the optimal route, timing and dosing warrant further studies.

Mo1431The Use of Additional Sampling Methods and Molecular Markersin the Diagnosis of Cytology Negative Biliary StricturesTamas A. Gonda, Michael P. Glick, Amrita Sethi, John M. Poneros,Susana Gonzalez, Peter D. StevensDivision of Digestive and Liver Diseases, Columbia UNiversity MedicalCenter, New York, NYINTRODUCTION. Biliary stenoses that are not associated with a mass, metastasisor recent stone disease and bile duct trauma remain difficult to diagnose byERCP. These strictures are often concerning for a malignancy and an accuratediagnosis is critical for further planning of therapy. Although brush cytology, themainstay of diagnosis, has a very high specificity, the sensitivity is very low. Thegoal of our study was to evaluate the additional yield of targeted samplingmethods and molecular markers in the diagnosis of bile duct cancer. METHODS.We conducted a retrospective review of all indeterminate biliary stricturesevaluated at our institution over a three year period and identified those with afinal diagnosis of malignancy. A cytology result was considered positive when itwas read as “malignant” or “suspicious” by a cytopathologist. In false negativecytology cases we identified all patients who underwent biliary biopsy,cholangioscopic targeted biopsies, biliary aspiration and EUS/FNA as well asFISH. FISH was performed using CEP3, 7 and 17 probes for chromosomeenumeration and 9p21 for deletion and we evaluated the performance of bothpolysomy alone and polysomy combined with the presence of 9p21 deletion.RESULTS. There were 124 biliary strictures and 42 of them were later diagnosedas malignant. Initial cytology was positive in 14 (sensitivity of cytology was 33%).The sensitivity of the additional diagnostic modalities is described in the Table.Among the 28 patients with, false negative cytology direct biopsy was performedin 14, cholangioscopic biopsy in 9, biliary aspiration in 9 and EUS FNA in 17.FISH was performed in all cases and was interpretable in 26. The yield of thesetests in cases when cytology was negative is shown below. Among all cases thatwere negative by cytology, FISH polysomy or 9p21 deletion was the singlediagnostic modality in 15/28 cases. Among the 10 false negative cases by bothcytology and FISH, one was diagnosed by cholangioscopic biopsy and two byEUS/FNA. CONCLUSIONS. These data suggest that FISH should always beincluded in the diagnosis of indeterminate strictures as this method offers highersensitivity and yield then any other sampling modality. In relatively rareinstances targeted biopsy may yield diagnosis when FISH or cytology does not.

Sensitivity and yield of molecular markers and additional sampling methods inthe diagnosis of biliary malignancy

Sensitivity

Yield inFalse

Negative(FN) cases

by cytology(n�28)

Yield in FN cases bycytology and FISH

(n�10)

Biopsy 35 1/9 (11%) 0/4Cholangioscopic Biopsy 44 3/7 (42%) 1/3Aspirate 0 0/8 (0%) 0/4EUS FNA 29 2/10 (20%) 2/5FISH polysomy 55 12/26 (46 %)FISH polysomy/9p21 deletion 73 17/26 (65%)

Mo1432Self Expandable Metal Stents for Anastomotic StrictureFollowing Liver Transplant: Should We Go Back to PlasticStenting?Jorge Cerecedo-Rodriguez, Melissa S. Phillips, Paola Figueroa-Barojas,Monica Gaidhane, Timothy M. Schmitt, Sean C. Kumer, Michel KahalehDigestive Health, University of Virginia, Charlottesville, VABackground: Biliary complications are frequent after liver transplantation (LT), withan incidence range of 7-51%. Endoscopic treatment with plastic stent placement hasbeen preferred since it is a less invasive alternative to surgical management. The useof self-expandable metal stents (SEMS) has been reported in post-LT strictures. Theaim of this study was to compare the success rates of three types of covered self-expandable metal stents (CSEMS) for the treatment of post-LT strictures. Methods:Data from patients who had undergone LT with biliary strictures were retrieved froma prospectively established database. Patients receiving covered metal stent weredivided into three groups. Group A received partially CSEMS (Wallstent, BostonScientific), Group B received fully CSEMS with fins (Viabil, Conmed), and Group Creceived fully CSEMS with flared ends (Wallflex, Boston Scientific). Technicalsuccess, stricture resolution, number of ERCP procedures, follow up, immediate andlate complications were recorded. Results: A total of 55 patients were included.There were 19 patients in Group A (14 male, mean age 52�10.83 [range 29-70]), 21patients in Group B (14 male, mean age 55�7.43 [range 43-70]) and 15 patients inGroup C (12 male, mean age 58.53�6.68 [range 46-71]). The indications fortransplantation included Hepatitis C virus (A�7, B�9, C�4), alcoholic liver disease(A�3, B�2, C�5) and other diagnosis (A�9, B�10, C�6). There were nostatistically significant differences between groups with regards to demographics.The CSEMS were successfully deployed in all 55 cases. The was no evidence ofsignificant difference with regards to stricture resolution (14 [73.68%] vs. 15 [71.42%]vs. 9 [75%] p�0.6630, df�2) or complications between groups. There was 1 post-ERCP pancreatitis in group B. Stent-related complications were as follows: 3 ingroup A (2 proximal stent migrations and 1 stent occlusion), 5 in group B (4 stentocclusions and 1 proximal migration), and 1 proximal migration in group C(p�0.3894, df�2). There were no complications reported during the removal of thestents. A total of 3 cases required surgery (hepatico-jejunostomy) due to refractorystrictures. One non-procedure-related death was reported in Group C. Conclusions:Global success rate of CSEMS (70.37%) proved to be unsatisfactory. There were nosignificant differences between stent types. Occlusion and migration were the mainfailure causes. These results need to be confirmed in a randomized multicenter trial.

Table 1. Patient characteristics (n�55)

Group A Group B Group C p-value

WALLSTENT Gore Viabil WALLFLEXNumber of

patients19 21 15

Age y, mean(range)

52.31�10.83 (29-70) 55.42�7.43 (43-70) 58.53�6.68 (46-71) 0.12

Male/Female 14/5 14/7 12/3 0.679 (df�2)Indication for

transplantationHCV 7 9 4ETOH 3 2 5 0.465 (df�4)Other 9 10 6Days to Stent

removal130.72�95.73

(24-393)125�69.21

(17-266)136.91�105.62

(22-401)0.925

ERCPs previousto CSEMS

2.6�2.1 (0-7) 0.62�1.12 (0-4) 1.2�1.89 (0-7) 0.002

Total ERCPs 6.79�4.59 (2-18) 3.48�1.75 (2-8) 2.93�1.71 (1-8) 0.001Follow up after

removal(mo)

38.94�22.31 (1-78) 24.27�9.50 (5-40) 4.62�3.37 (0.03-11) �0.001

Abstracts

www.giejournal.org Volume 73, No. 4S : 2011 GASTROINTESTINAL ENDOSCOPY AB343