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Allopurinol to Prevent Pancreatitis After Endoscopic Retrograde Cholangiopancreatography (ERCP): A Randomized Placebo-Controlled Trial
Abstracts
W1615 Allopurinol to Prevent Pancreatitis After Endoscopic Retrograde Cholangiopancreatography (ERCP): A Randomized Placebo-Controlled Trial Joseph Romagnuolo, Robert J. Hilsden, Gurpal S. Sandha, Martin J. Cole, Sydney Bass, Gary R. May, Jonathan R. Love, Vincent G. Bain, John P. Mckaigney, Richard Fedorak Background: ERCP is associated with a risk of pancreatitis (PEP). Animal studies suggest that a single dose of allopurinol (xanthine oxidase inhibitor with high oral bioavailability and long-lasting active metabolites) may reduce the PEP incidence, but human studies have had conflicting results. Aim: To determine if allopurinol decreases the rate of PEP. Methods: Patients referred for ERCP to 9 endoscopists at 2 tertiary centers were randomized to receive either allopurinol 300 mg or identical placebo orally 60 min (þ/-20) prior to ERCP, stratified according to highrisk ERCP (manometry or pancreatic therapy). The primary outcome (PEP) was blindly adjudicated, and pancreatitis was defined according to the Cotton consensus, and was evaluated at 48h and 30 days. Secondary outcomes included severe PEP, length of stay, and mortality (nil). The trial was terminated after the blinded (midpoint) interim analysis, as recommended by the independent data and safety monitoring committee. Results: We randomized 586 subjects, 293 to each arm. The crude PEP rates were 5.5% (allopurinol) and 4.1% (placebo), (p Z 0.44; differenceZ1.4% [95% CI: -2.1% to 4.8%]. The Mantel-Haenszel combined risk ratio for PEP with allopurinol, considering stratification, was 1.37 (95% CI: 0.65 to 2.86). Subgroup analyses suggested a non-significant trend towards a possible benefit in the high risk group, and possible harm for the remaining subjects. Logistic regression found pancreatic therapy, pancreatic injection, and prior PEP to be the only independent predictors of outcome. Conclusion: Allopurinol does not appear to reduce the overall risk of PEP; however, its potential benefit in the high-risk group (but potential harm for non-high-risk patients) means further study is required.)Sponsored by a CAG/CIHR Young Investigator Award
W1616 Fatty Pancreas- A Risk Factor for the Development of SOD-Pancreatitis Abhishek Mathur, Kumar Sandrasegaran, Nicholas J. Zyromski, Megan B. Marine, Stuart Sherman, Glen A. Lehman, Henry A. Pitt Introduction: Adipose tissue has recently been characterized as an endocrine organ which secretes proinflammatory adipocytokines including leptin, TNF-a, IL6, and IL-1b. Visceral steatosis results in a local inflammatory mileu resulting in organ dysfunction with nonalcoholic steatohepatitis being a well established example of this phenomenon. Previous data from our lab have shown that obese mice with increased pancreatic fat have elevated inflammatory adipocytokines. In addition, these mice with increased fat in their pancreas develop more severe pancreatitis when challenged with cerulein. Sphincter of Oddi dysfunction (SOD) with pancreatic sphincter hypertension most commonly presents with abdominal pain or pancreatitis. However, the factors determining the progression to SODinduced pancreatitis remain unknown. A fatty pancreas has not previously been considered as a contributing factor in the development of SOD-pancreatitis. Therefore, we hypothesized that patients who develop SOD-pancreatitis are more likely to have elevated pancreatic fat. Methods: Sixteen patients with SOD and manometrically documented pancreatic sphincter hypertension were studied. All patients had magnetic resonance image (MRI) evaluation. Seven patients (SODcontrols) were symptomatic for abdominal pain without evidence of biochemical pancreatitis (elevated serum amylase/lipase). Nine patients had pancreatitis (SODpancreatitis) with documented enzyme elevation. Fat in the abdominal wall, pancreatic head, body and tail and right liver lobe were measured by MRI. The percentage fat was determined by recording the signal intensity in the in-phase (Sin) and out-of phase (Sout) T1-weighted gradient echo sequences and subsequently calculating the fat fraction (Sin- Sout)/(Sin X 2). Data were analyzed by Student’s t test. Results: SOD-controls and SOD- pancreatitis patients did not differ with respect to age (45 vs 47 years), gender (71% vs 67% female), weight (88 vs 83 kg), and abdominal wall fat thickness (37 vs 42 mm). The percentage of fat in the pancreatic head, body and tail and liver are shown in the table. Conclusions: These data suggest that patients with SOD-pancreatitis have more pancreatic fat in both the body and tail of the pancreas than symptomatic SOD patients-without pancreatitis. Therefore, we conclude that fatty pancreas is a significant risk factor in the development of pancreatitis in patients with sphincter of Oddi dysfunction.
SOD-Controls SOD-Pancreatitis
Pancreas- Head 4.0 2.3 5.6 2.4
Pancreas- Body 0.3 0.3 7.6 2.4)
Pancreas- Tail 1.1 0.5 8.2 2.5)
Liver 5.3 3.9 8.7 4.5
)p ! 0.05 vs Controls
AB328 GASTROINTESTINAL ENDOSCOPY Volume 67, No. 5 : 2008
W1617 Can Wire-Guided Cannulation (WGC) Prevent Post-ERCP Pancreatitis? A Prospective Randomized Trial Do Hyun Park, Tae Hoon Lee, Ji-Young Park, Jeong Hoon Park, Suck-Ho Lee, Il Kwun Chung, Hong-Soo Kim, Sang-Heum Park, Sun-Joo Kim Background and Aims: Among procedure-related factors associated with post ERCP pancreatitis, selective cannulation of the common bile duct by insertion of guide wire may be associated with fewer complications than conventional methods of cannulation using contrast injection for accessing the bile duct. However, the results of studies of the usefulness of wire-guided cannulation (WGC) are conflicting. This prospective randomized trial was designed to determine whether post ERCP pancreatitis can be avoided by wire-guided biliary cannulation following contrast injection. Patients and Methods: We prospectively randomized 300 patients to WGC or conventional cannulation. A single endoscope (D.H.P.) was used to perform all procedures. In WGC, a hydrophilic tipped guide wire (Jagwire; Boston Scientific), 0.035 inch in diameter, was preloaded in the pull type papillotome (Flowcut, Olympus). The guide wire was advanced through the bile duct under fluoroscopy. After biliary cannulation was achieved with a guide wire insertion, contrast injection was performed. In control, the standard technique was used for cannulation of the bile duct with a papillotome and injection of contrast medium. Five attempts of cannulation were allowed in both groups. Prophylactic p-duct stenting was not performed in any patient. Results: Accidental main pancreatic duct cannulations were 39 patients (26%) in WGC and 44 patients (29%) in control (P Z NS), a needle-knife fistulotomy as a rescue management for difficult cannulation was performed in 28 patients (19%) in WGC and 36 patients (24%) in control (P Z NS), respectively. Three patients (2%) in WGC and seventeen patients (11%) in control developed post ERCP pancreatitis, P Z 0.001. Among the cases of acute pancreatitis in WGC, two patients with sphincter of Oddi dysfunction (SOD) showed post-ERCP pancreatitis (one moderate, and one severe) despite the use of WGC. In multivariate analysis, WGC was a protective factor, whereas female and SOD were risk factors for post-ERCP pancreatitis. (Table 1) Conclusions: We found that wire-guided cannulation (WGC) followed by injection of contrast can prevent post ERCP pancreatitis in a low risk cohort (SOD ! 2%). In our study, however, WGC may not prevent post-ERCP pancreatitis in patients with suspected SOD. Further prospective comparative studies of the role of WGC in high risk cohorts should be conducted to confirm our study. Result of Logistic Regression on Variables With Regard To Post-ERCP Pancreatits Guidewire Gender (female) SOD
Odds ratio 0.11 3.2 23.7
95% confidence interval 0.02-0.05 1.11-9.40 2.44-230.18
P-value 0.004 0.032 0.006
W1618 5 Fr Prophylactic Pancreatic Stents Are Easier to Place and Require Fewer Guide Wires Than 3 Fr Stents Syed M. Abbas Fehmi, Philip S. Schoenfeld, James M. Scheiman, Richard S. Kwon, Cyrus R. Piraka, Erik-Jan Wamsteker, Sheryl Korsnes, Michelle A. Anderson, Grace H. Elta Background: Prophylactic temporary pancreatic duct (PD) stenting decreases postERCP pancreatitis (PEP) in high-risk patients although the best type of stent to use remains controversial. Aim: Compare the spontaneous passage rates, ease of placement, and number of wires used for 3 Fr 6 cm [3F] versus 5 Fr 5 cm [5F] (both single pigtail, no flaps). Methods: High risk patients or procedures are defined as pancreatic sphincterotomy (ES), minor papilla ES, suspected or confirmed SOD, ampullectomy, pre-cut ES, h/o PEP and difficult cannulation. Patients were randomly assigned a 3F or 5F stent using concealed allocation. The endoscopist was blinded to Rx group until decision was made to place a stent. If the initial stent could not be placed, an alternative one could be used. The stent placed, time required for stent placement, ease of placement (using a 5 point Likert scale) and number of guide wires used were recorded. X-ray was done on day 14 to document spontaneous passage. PEP was defined clinically by the presence of abdominal discomfort and amylase or lipase O 3x ULN. Analyses use an ITT protocol. Results: 23 patients have been enrolled with placement of either 3F [52% (12/23)] or 5F [48% (11/23)] stent. The average age of our cohort is 41 years (87% women). The indications for stent placement are similar between the two groups. Spontaneous passage of stents for 3F vs. 5F [92% (11/12) vs. 82% (9/11), p Z 0.59] and rates of PEP (all mild) for 3F vs. 5F [33% (4/12) vs. 18% (2/11), p Z 0.64] are not significantly different. Ease of placement of the 5F stent is significantly better compared to the 3F group (p Z 0.02). Proportion of endoscopists reporting the categories of ‘‘difficult’’ or ‘‘very difficult’’ ease of placement in the 3F group is also higher than in the 5F group (p Z 0.05). Mean number of guide wires used with the 3F stent is significantly more compared to the 5F group (p Z 0.001). Proportion of subjects requiring the use of more than 1 guide wire is also significantly more in the 3F group (p Z 0.005). The difference in mean time required for placement of 3F (14 mins) and 5F (11 mins) stents was not significant. Mean time required for stent
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W1615 Allopurinol to Prevent Pancreatitis After Endoscopic Retrograde Cholangiopancreatography (ERCP): A Randomized Placebo-Controlled Trial Joseph Romagnuolo, Robert J. Hilsden, Gurpal S. Sandha, Martin J. Cole, Sydney Bass, Gary R. May, Jonathan R. Love, Vincent G. Bain, John P. Mckaigney, Richard Fedorak Background: ERCP is associated with a risk of pancreatitis (PEP). Animal studies suggest that a single dose of allopurinol (xanthine oxidase inhibitor with high oral bioavailability and long-lasting active metabolites) may reduce the PEP incidence, but human studies have had conflicting results. Aim: To determine if allopurinol decreases the rate of PEP. Methods: Patients referred for ERCP to 9 endoscopists at 2 tertiary centers were randomized to receive either allopurinol 300 mg or identical placebo orally 60 min (þ/-20) prior to ERCP, stratified according to highrisk ERCP (manometry or pancreatic therapy). The primary outcome (PEP) was blindly adjudicated, and pancreatitis was defined according to the Cotton consensus, and was evaluated at 48h and 30 days. Secondary outcomes included severe PEP, length of stay, and mortality (nil). The trial was terminated after the blinded (midpoint) interim analysis, as recommended by the independent data and safety monitoring committee. Results: We randomized 586 subjects, 293 to each arm. The crude PEP rates were 5.5% (allopurinol) and 4.1% (placebo), (p Z 0.44; differenceZ1.4% [95% CI: -2.1% to 4.8%]. The Mantel-Haenszel combined risk ratio for PEP with allopurinol, considering stratification, was 1.37 (95% CI: 0.65 to 2.86). Subgroup analyses suggested a non-significant trend towards a possible benefit in the high risk group, and possible harm for the remaining subjects. Logistic regression found pancreatic therapy, pancreatic injection, and prior PEP to be the only independent predictors of outcome. Conclusion: Allopurinol does not appear to reduce the overall risk of PEP; however, its potential benefit in the high-risk group (but potential harm for non-high-risk patients) means further study is required.)Sponsored by a CAG/CIHR Young Investigator Award
W1616 Fatty Pancreas- A Risk Factor for the Development of SOD-Pancreatitis Abhishek Mathur, Kumar Sandrasegaran, Nicholas J. Zyromski, Megan B. Marine, Stuart Sherman, Glen A. Lehman, Henry A. Pitt Introduction: Adipose tissue has recently been characterized as an endocrine organ which secretes proinflammatory adipocytokines including leptin, TNF-a, IL6, and IL-1b. Visceral steatosis results in a local inflammatory mileu resulting in organ dysfunction with nonalcoholic steatohepatitis being a well established example of this phenomenon. Previous data from our lab have shown that obese mice with increased pancreatic fat have elevated inflammatory adipocytokines. In addition, these mice with increased fat in their pancreas develop more severe pancreatitis when challenged with cerulein. Sphincter of Oddi dysfunction (SOD) with pancreatic sphincter hypertension most commonly presents with abdominal pain or pancreatitis. However, the factors determining the progression to SODinduced pancreatitis remain unknown. A fatty pancreas has not previously been considered as a contributing factor in the development of SOD-pancreatitis. Therefore, we hypothesized that patients who develop SOD-pancreatitis are more likely to have elevated pancreatic fat. Methods: Sixteen patients with SOD and manometrically documented pancreatic sphincter hypertension were studied. All patients had magnetic resonance image (MRI) evaluation. Seven patients (SODcontrols) were symptomatic for abdominal pain without evidence of biochemical pancreatitis (elevated serum amylase/lipase). Nine patients had pancreatitis (SODpancreatitis) with documented enzyme elevation. Fat in the abdominal wall, pancreatic head, body and tail and right liver lobe were measured by MRI. The percentage fat was determined by recording the signal intensity in the in-phase (Sin) and out-of phase (Sout) T1-weighted gradient echo sequences and subsequently calculating the fat fraction (Sin- Sout)/(Sin X 2). Data were analyzed by Student’s t test. Results: SOD-controls and SOD- pancreatitis patients did not differ with respect to age (45 vs 47 years), gender (71% vs 67% female), weight (88 vs 83 kg), and abdominal wall fat thickness (37 vs 42 mm). The percentage of fat in the pancreatic head, body and tail and liver are shown in the table. Conclusions: These data suggest that patients with SOD-pancreatitis have more pancreatic fat in both the body and tail of the pancreas than symptomatic SOD patients-without pancreatitis. Therefore, we conclude that fatty pancreas is a significant risk factor in the development of pancreatitis in patients with sphincter of Oddi dysfunction.
SOD-Controls SOD-Pancreatitis
Pancreas- Head 4.0 2.3 5.6 2.4
Pancreas- Body 0.3 0.3 7.6 2.4)
Pancreas- Tail 1.1 0.5 8.2 2.5)
Liver 5.3 3.9 8.7 4.5
)p ! 0.05 vs Controls
AB328 GASTROINTESTINAL ENDOSCOPY Volume 67, No. 5 : 2008
W1617 Can Wire-Guided Cannulation (WGC) Prevent Post-ERCP Pancreatitis? A Prospective Randomized Trial Do Hyun Park, Tae Hoon Lee, Ji-Young Park, Jeong Hoon Park, Suck-Ho Lee, Il Kwun Chung, Hong-Soo Kim, Sang-Heum Park, Sun-Joo Kim Background and Aims: Among procedure-related factors associated with post ERCP pancreatitis, selective cannulation of the common bile duct by insertion of guide wire may be associated with fewer complications than conventional methods of cannulation using contrast injection for accessing the bile duct. However, the results of studies of the usefulness of wire-guided cannulation (WGC) are conflicting. This prospective randomized trial was designed to determine whether post ERCP pancreatitis can be avoided by wire-guided biliary cannulation following contrast injection. Patients and Methods: We prospectively randomized 300 patients to WGC or conventional cannulation. A single endoscope (D.H.P.) was used to perform all procedures. In WGC, a hydrophilic tipped guide wire (Jagwire; Boston Scientific), 0.035 inch in diameter, was preloaded in the pull type papillotome (Flowcut, Olympus). The guide wire was advanced through the bile duct under fluoroscopy. After biliary cannulation was achieved with a guide wire insertion, contrast injection was performed. In control, the standard technique was used for cannulation of the bile duct with a papillotome and injection of contrast medium. Five attempts of cannulation were allowed in both groups. Prophylactic p-duct stenting was not performed in any patient. Results: Accidental main pancreatic duct cannulations were 39 patients (26%) in WGC and 44 patients (29%) in control (P Z NS), a needle-knife fistulotomy as a rescue management for difficult cannulation was performed in 28 patients (19%) in WGC and 36 patients (24%) in control (P Z NS), respectively. Three patients (2%) in WGC and seventeen patients (11%) in control developed post ERCP pancreatitis, P Z 0.001. Among the cases of acute pancreatitis in WGC, two patients with sphincter of Oddi dysfunction (SOD) showed post-ERCP pancreatitis (one moderate, and one severe) despite the use of WGC. In multivariate analysis, WGC was a protective factor, whereas female and SOD were risk factors for post-ERCP pancreatitis. (Table 1) Conclusions: We found that wire-guided cannulation (WGC) followed by injection of contrast can prevent post ERCP pancreatitis in a low risk cohort (SOD ! 2%). In our study, however, WGC may not prevent post-ERCP pancreatitis in patients with suspected SOD. Further prospective comparative studies of the role of WGC in high risk cohorts should be conducted to confirm our study. Result of Logistic Regression on Variables With Regard To Post-ERCP Pancreatits Guidewire Gender (female) SOD
Odds ratio 0.11 3.2 23.7
95% confidence interval 0.02-0.05 1.11-9.40 2.44-230.18
P-value 0.004 0.032 0.006
W1618 5 Fr Prophylactic Pancreatic Stents Are Easier to Place and Require Fewer Guide Wires Than 3 Fr Stents Syed M. Abbas Fehmi, Philip S. Schoenfeld, James M. Scheiman, Richard S. Kwon, Cyrus R. Piraka, Erik-Jan Wamsteker, Sheryl Korsnes, Michelle A. Anderson, Grace H. Elta Background: Prophylactic temporary pancreatic duct (PD) stenting decreases postERCP pancreatitis (PEP) in high-risk patients although the best type of stent to use remains controversial. Aim: Compare the spontaneous passage rates, ease of placement, and number of wires used for 3 Fr 6 cm [3F] versus 5 Fr 5 cm [5F] (both single pigtail, no flaps). Methods: High risk patients or procedures are defined as pancreatic sphincterotomy (ES), minor papilla ES, suspected or confirmed SOD, ampullectomy, pre-cut ES, h/o PEP and difficult cannulation. Patients were randomly assigned a 3F or 5F stent using concealed allocation. The endoscopist was blinded to Rx group until decision was made to place a stent. If the initial stent could not be placed, an alternative one could be used. The stent placed, time required for stent placement, ease of placement (using a 5 point Likert scale) and number of guide wires used were recorded. X-ray was done on day 14 to document spontaneous passage. PEP was defined clinically by the presence of abdominal discomfort and amylase or lipase O 3x ULN. Analyses use an ITT protocol. Results: 23 patients have been enrolled with placement of either 3F [52% (12/23)] or 5F [48% (11/23)] stent. The average age of our cohort is 41 years (87% women). The indications for stent placement are similar between the two groups. Spontaneous passage of stents for 3F vs. 5F [92% (11/12) vs. 82% (9/11), p Z 0.59] and rates of PEP (all mild) for 3F vs. 5F [33% (4/12) vs. 18% (2/11), p Z 0.64] are not significantly different. Ease of placement of the 5F stent is significantly better compared to the 3F group (p Z 0.02). Proportion of endoscopists reporting the categories of ‘‘difficult’’ or ‘‘very difficult’’ ease of placement in the 3F group is also higher than in the 5F group (p Z 0.05). Mean number of guide wires used with the 3F stent is significantly more compared to the 5F group (p Z 0.001). Proportion of subjects requiring the use of more than 1 guide wire is also significantly more in the 3F group (p Z 0.005). The difference in mean time required for placement of 3F (14 mins) and 5F (11 mins) stents was not significant. Mean time required for stent
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