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Su1244 Comparable Efficacy of Low and High Dose Induction Corticosteroid Treatment in Autoimmune Pancreatitis
Using data from 515 patients with CP enrolled prospectively in the North American Pancreatitis II (NAPS2) Study, we evaluated how often endoscopic (biliary or pancreatic sphincterotomy, biliary stent placement, pancreatic stent placement, pancreatic duct stone removal) and surgical (pancreatic cyst removal, pancreatic drainage procedure, pancreatic resection, surgical sphincterotomy) therapies were performed and how the effectiveness of these interventions was perceived by the treating physicians. RESULTS: Biliary and/or pancreatic sphincterotomy was the most commonly attempted (42%) endoscopic procedure (biliary stent 14%; pancreatic stent 36%; pancreatic stone removal 11%; p<0.001). However, pancreatic stone removal was perceived as the most efficacious and sphincterotomy the least efficacious (70% vs. 40%; p<0.001). On multivariable analysis, the presence of abdominal pain (OR 1.82, 95% CI 1.15-2.88) was predictive of attempting endoscopic therapy, while having exocrine insufficiency (OR 0.63, 95% CI 0.42-0.94) deterred the use of endoscopy. Predictors of undergoing a sphincterotomy were having an obstructive etiology (OR 3.62, 95% CI 1.71-7.66), the presence of abdominal pain (OR 2.33, 95% CI 1.40-3.88), and having a genetic etiology (OR 2.06, 95% CI 1.04-4.10). An obstructive etiology was the only predictor (OR 2.56, 95% CI 1.22-5.34) for undergoing pancreatic duct stenting. Surgical therapies were all attempted equally (cyst removal 7%, drainage procedure 10%, resection procedure 12%) with the exception of surgical sphincteroplasty (4%, p<0.001). Surgical sphincteroplasty was also perceived to be the least effective therapy (46%, p<0.001) vs. cyst removal (76%), drainage (71%) and resection (73%). On multivariable analysis, increasing age was negatively associated with the use of a surgical intervention (OR per 10 years 0.80, 95% CI 0.70-0.93) and resulted in a higher prevalence of exocrine insufficiency (OR 2.24, 95% CI 1.43-3.55). CONCLUSIONS: Endoscopic therapy is commonly used for treating chronic pancreatitis, with pancreatic duct stone removal perceived as the most effective. While surgical therapies are not performed as frequently as endoscopic therapies, especially in older patients, their rates (except sphincteroplasty) of perceived effectiveness tend to be higher than endoscopic therapies.
Su1244 Comparable Efficacy of Low and High Dose Induction Corticosteroid Treatment in Autoimmune Pancreatitis Jorie Buijs, Marianne J. Van Heerde, Bettina E. Hansen, Katharina Biermann, Frank P. Vleggaar, Menno A. Brink, Ernst J. Kuipers, Marco J. Bruno, Henk R. van Buuren
Su1246
Introduction: Autoimmune pancreatitis (AIP) is a distinct type of chronic pancreatitis highly responsive to corticosteroids. The usually recommended dosage of prednisone for remission induction is 0.6 mg/kg/day, resulting in daily starting doses of 30 - 60 mg. This recommended dosage is largely based on empirical data and lacks scientific base. Potentially, high dose corticosteroid treatment is associated with significant side effects, particularly in a population characterised by relative advanced age, diabetes and obstructive jaundice at presentation. The rationale for high dose treatment could also be questioned considering the well-established sensitivity for corticosteroids in AIP patients. We therefore compared the efficacy of treatment and the incidence of worsening glucose tolerance in AIP patients treated with different doses of steroid induction therapy. Methods: A retrospective survey was conducted of patients diagnosed with AIP between May 1992 and August 2011. Clinical, laboratory and image findings were assessed before treatment and at 1, 3 and 6 months after starting treatment. Differences between groups treated with different initial doses of prednisone were compared using linear and logistic regression analysis. Results: A total of 37 patients (33 males; median age 65 years) were included. The most frequent presenting symptoms included jaundice, pancreatic insufficiency, weight loss and (mild) abdominal pain. Four patients were treated with an initial dose of prednisone of 10 mg/d, 2 patients with 15 mg/d, 6 patients with 20 mg/d, 11 patients with 30 mg/d, 12 patients with 40 mg/d and 2 patients with 60 mg/d. With respect to the baseline characteristics including gender, age, presenting symptoms, laboratory and imaging results, there was no significant difference in administered dose of prednisone. During a clinical follow-up period of 6 months, 37/38 (97%) patients achieved clinical response. Symptomatic response after 1, 3 and 6 months of treatment was not associated with doses of prednisone. Treatment response according to imaging studies and laboratory parameters was also comparable. There was no significant difference in worsening of glucose tolerance. (Table 1) Conclusions: Symptomatic, radiological and biochemical improvement was comparable for AIP patients treated with variable induction doses of prednisone. Based on these retrospective data it may be questioned whether high dose prednisone therapy is truly indicated in patients presenting with AIP. Table 1. Response to steroid therapy at 6 months
Evidence of Chronic Pancreatitis in Patients With Unexplained Recurrent Acute Pancreatitis: Implications to Understanding the Early Stages of Tropical Chronic Pancreatitis Madhava Pai Kanhangad, C Ganesh Pai, Ganesh Bhat, Deepak Suvarna Background & Aims: Tropical chronic pancreatitis (TCP) was originally described as a disease of under-nutrition characterised by early onset of abdominal pain, a high frequency of diabetes mellitus, steattorrhoea and pancreatic calcification, and a reduced life expectancy. The clinical presentation of TCP has changed over recent decades to a milder form of disease, later onset of symptoms, lesser degree of functional impairment and calcification, and better nutritional status. We aimed to assess the frequency of chronic pancreatitis in patients with unexplained recurrent acute pancreatitis (RAP) presenting to a centre where TCP is common. Methods: Patients with two or more episodes of documented acute pancreatitis in whom no cause was evident on clinical (alcohol consumption) and laboratory (hypercalcaemia, hypertriglyceridaemia) evaluation and on cross sectional imaging (biliary calculi, tumours) were prospectively included. They were evaluated by EUS for changes of chronic pancreatitis (CP) using Rosemont Criteria. Findings of endoscopic retrograde cholangiopancreatography (ERCP) as per Cambridge Criteria were also considered in the subgroup in which this procedure was indicated for therapy. Results: Forty-eight patients (male: female = 37:11, median age = 21, range 10 -70 years) with RAP seen over a 34-month period beginning January 2009 were included prospectively. All underwent EUS and 19 (39.6%) underwent ERCP. EUS finding were most consistent for CP and suggestive of CP in 7 (14.6%) and 11 (22.9%) patients respectively. Two (4.2%) others developed findings most consistent with CP on repeat EUS during the study period. An additional 5 (10.4%) had mild or moderate changes of CP on ERCP. Thus, 25 (52.1%) patients showed findings most consistent with or suggestive of CP on EUS, or of mild to moderate changes of CP on ERCP during the study period. Conclusions: Our data suggests that TCP evolves through stages of RAP, and that recurrent episodes of inflammation might contribute to the development of chronic disease. Prospective follow up studies are needed to confirm this. This opens up the possibility of focusing on earlier stages of this condition to see if early interventions will alter the outcomes in these patients. Su1247 The Role of TRPV1 in Ethanol Plus Fatty Acid-Induced Acute Pancreatitis in Mice Steven R. Vigna, Rafiq A. Shahid, Rodger A. Liddle
1 Linear regression analysis 2 Logistic regression analysis increased glucose levels in pre-existing diabetes mellitus
3
Background: Alcohol abuse is well-known to be associated with pancreatitis in people but the mechanism is unknown. A new model of murine pancreatitis caused by treatment with both ethanol (EtOH) and the fatty acid, palmitoleic acid (POA), a nonoxidative metabolite of EtOH, has recently been described. Transient receptor potential vanilloid-1 (TRPV1) is a cation channel that is expressed by primary sensory afferent nerves. TRPV1 activation results in release of proinflammatory neurotransmitters such as substance P. TRPV1 has been shown by others to be activated by EtOH. We proposed that EtOH may lower the activation threshold of TRPV1 and predispose to acute pancreatitis. Therefore, in the present work we evaluated the role of TRPV1 in acute pancreatitis caused by EtOH + POA. Methods: Acute inflammation of the pancreas was stimulated by ip injection twice one hour apart of 1.32 g/kg EtOH + 2 mg/kg POA in wild type C57Bl/6 mice and TRPV1 knockout C57Bl/ 6 mice. Treatment with EtOH alone or POA alone at these doses had no inflammatory effects. The mice were killed 24 hours later and the pancreas was weighed and harvested for subsequent myeloperoxidase (MPO) assay and histopathological analysis. Blood was also collected for serum amylase measurement. Results: EtOH + POA caused statistically significant increases in serum amylase levels, pancreatic MPO levels, and histopathology (P < 0.050.001 vs vehicle controls); pancreatic edema was elevated but not significantly. Pretreatment of the wild type mice 30 min before EtOH + POA injection with the TRPV1 antagonist drug, AMG9810, at a dose of 30 mg/kg ip resulted in reductions in serum amylase levels (89 ± 11%; P < 0.05), pancreatic edema (21 ± 20%), pancreatic MPO levels (58 ± 25%), and histopathology (78 ± 13%; P < 0.001) vs EtOH + POA alone. Similarly, EtOH + POA
New onset diabetes mellitus or
Su1245 Spectrum of use and Perceived Effectiveness of Endoscopic and Surgical Therapies for Chronic Pancreatitis in the United States Lisa M. Glass, Dhiraj Yadav, Elizabeth Kennard, Joseph Romagnuolo, Michelle A. Anderson, David C. Whitcomb, Timothy B. Gardner BACKGROUND & AIMS: Effectiveness of endoscopic and surgical therapies for treating chronic pancreatitis (CP) in the United States has been limited to small studies of selected patients. We aimed to describe the frequency of use and perceived effectiveness of endoscopic and surgical therapies in adult patients with CP treated at US referral centers. METHODS:
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AGA Abstracts
AGA Abstracts
infusions every 2-3 months for two years. Medical records were reviewed and patients interviewed for follow-up. Data were abstracted on patient demographics, indications for RTX therapy and evidence of symptomatic, biochemical and radiographic disease response and relapse, if any. Results: Eleven male patients (mean age 66 years, 64% IgG4 seropositive) were treated with RTX. The disease indications for RTX treatment were IgG4-related sclerosing cholangitis (n=6), autoimmune pancreatitis (diffuse enlargement or focal mass) (n=5), and other organ involvement (n=2). Indications for use of RTX were relapse on immunomodulator (n=5), prednisone intolerance (n=4), or relapse on prednisone (n=2). Initiation of RTX began a median of 22 months following initial diagnosis of IgG4-RD, and patients were followed for a median of 6 months (0-60 months) after their first infusion. Each of the 10 patients who have completed the 4 dose induction regimen demonstrated either a partial or complete biochemical and/or radiographic response. In patients with abnormal liver tests prior to starting rituximab (n=5), normalization of tests was documented at a median 2.8 months from the initial infusion. Radiographic response was documented at a median 4.4 months (2.3-9.9 months). Remission was achieved without the use of concomitant steroids in 8 patients. One patient experienced a subsequent relapse >2 years after completing the RTX protocol. One patient developed neutropenia after 4 doses, and one patient developed interstitial lung infiltrates that are potentially attributable to RTX. Conclusions: Rituximab monotherapy can induce remission in IgG4-RD, even in those patients who are refractory or intolerant to either steroids or immunomodulators. Biochemical and radiographic responses are usually seen within 3-4 months. Treatment is well-tolerated and relapses are not seen while on treatment.
Su1244 Comparable Efficacy of Low and High Dose Induction Corticosteroid Treatment in Autoimmune Pancreatitis Jorie Buijs, Marianne J. Van Heerde, Bettina E. Hansen, Katharina Biermann, Frank P. Vleggaar, Menno A. Brink, Ernst J. Kuipers, Marco J. Bruno, Henk R. van Buuren
Su1246
Introduction: Autoimmune pancreatitis (AIP) is a distinct type of chronic pancreatitis highly responsive to corticosteroids. The usually recommended dosage of prednisone for remission induction is 0.6 mg/kg/day, resulting in daily starting doses of 30 - 60 mg. This recommended dosage is largely based on empirical data and lacks scientific base. Potentially, high dose corticosteroid treatment is associated with significant side effects, particularly in a population characterised by relative advanced age, diabetes and obstructive jaundice at presentation. The rationale for high dose treatment could also be questioned considering the well-established sensitivity for corticosteroids in AIP patients. We therefore compared the efficacy of treatment and the incidence of worsening glucose tolerance in AIP patients treated with different doses of steroid induction therapy. Methods: A retrospective survey was conducted of patients diagnosed with AIP between May 1992 and August 2011. Clinical, laboratory and image findings were assessed before treatment and at 1, 3 and 6 months after starting treatment. Differences between groups treated with different initial doses of prednisone were compared using linear and logistic regression analysis. Results: A total of 37 patients (33 males; median age 65 years) were included. The most frequent presenting symptoms included jaundice, pancreatic insufficiency, weight loss and (mild) abdominal pain. Four patients were treated with an initial dose of prednisone of 10 mg/d, 2 patients with 15 mg/d, 6 patients with 20 mg/d, 11 patients with 30 mg/d, 12 patients with 40 mg/d and 2 patients with 60 mg/d. With respect to the baseline characteristics including gender, age, presenting symptoms, laboratory and imaging results, there was no significant difference in administered dose of prednisone. During a clinical follow-up period of 6 months, 37/38 (97%) patients achieved clinical response. Symptomatic response after 1, 3 and 6 months of treatment was not associated with doses of prednisone. Treatment response according to imaging studies and laboratory parameters was also comparable. There was no significant difference in worsening of glucose tolerance. (Table 1) Conclusions: Symptomatic, radiological and biochemical improvement was comparable for AIP patients treated with variable induction doses of prednisone. Based on these retrospective data it may be questioned whether high dose prednisone therapy is truly indicated in patients presenting with AIP. Table 1. Response to steroid therapy at 6 months
Evidence of Chronic Pancreatitis in Patients With Unexplained Recurrent Acute Pancreatitis: Implications to Understanding the Early Stages of Tropical Chronic Pancreatitis Madhava Pai Kanhangad, C Ganesh Pai, Ganesh Bhat, Deepak Suvarna Background & Aims: Tropical chronic pancreatitis (TCP) was originally described as a disease of under-nutrition characterised by early onset of abdominal pain, a high frequency of diabetes mellitus, steattorrhoea and pancreatic calcification, and a reduced life expectancy. The clinical presentation of TCP has changed over recent decades to a milder form of disease, later onset of symptoms, lesser degree of functional impairment and calcification, and better nutritional status. We aimed to assess the frequency of chronic pancreatitis in patients with unexplained recurrent acute pancreatitis (RAP) presenting to a centre where TCP is common. Methods: Patients with two or more episodes of documented acute pancreatitis in whom no cause was evident on clinical (alcohol consumption) and laboratory (hypercalcaemia, hypertriglyceridaemia) evaluation and on cross sectional imaging (biliary calculi, tumours) were prospectively included. They were evaluated by EUS for changes of chronic pancreatitis (CP) using Rosemont Criteria. Findings of endoscopic retrograde cholangiopancreatography (ERCP) as per Cambridge Criteria were also considered in the subgroup in which this procedure was indicated for therapy. Results: Forty-eight patients (male: female = 37:11, median age = 21, range 10 -70 years) with RAP seen over a 34-month period beginning January 2009 were included prospectively. All underwent EUS and 19 (39.6%) underwent ERCP. EUS finding were most consistent for CP and suggestive of CP in 7 (14.6%) and 11 (22.9%) patients respectively. Two (4.2%) others developed findings most consistent with CP on repeat EUS during the study period. An additional 5 (10.4%) had mild or moderate changes of CP on ERCP. Thus, 25 (52.1%) patients showed findings most consistent with or suggestive of CP on EUS, or of mild to moderate changes of CP on ERCP during the study period. Conclusions: Our data suggests that TCP evolves through stages of RAP, and that recurrent episodes of inflammation might contribute to the development of chronic disease. Prospective follow up studies are needed to confirm this. This opens up the possibility of focusing on earlier stages of this condition to see if early interventions will alter the outcomes in these patients. Su1247 The Role of TRPV1 in Ethanol Plus Fatty Acid-Induced Acute Pancreatitis in Mice Steven R. Vigna, Rafiq A. Shahid, Rodger A. Liddle
1 Linear regression analysis 2 Logistic regression analysis increased glucose levels in pre-existing diabetes mellitus
3
Background: Alcohol abuse is well-known to be associated with pancreatitis in people but the mechanism is unknown. A new model of murine pancreatitis caused by treatment with both ethanol (EtOH) and the fatty acid, palmitoleic acid (POA), a nonoxidative metabolite of EtOH, has recently been described. Transient receptor potential vanilloid-1 (TRPV1) is a cation channel that is expressed by primary sensory afferent nerves. TRPV1 activation results in release of proinflammatory neurotransmitters such as substance P. TRPV1 has been shown by others to be activated by EtOH. We proposed that EtOH may lower the activation threshold of TRPV1 and predispose to acute pancreatitis. Therefore, in the present work we evaluated the role of TRPV1 in acute pancreatitis caused by EtOH + POA. Methods: Acute inflammation of the pancreas was stimulated by ip injection twice one hour apart of 1.32 g/kg EtOH + 2 mg/kg POA in wild type C57Bl/6 mice and TRPV1 knockout C57Bl/ 6 mice. Treatment with EtOH alone or POA alone at these doses had no inflammatory effects. The mice were killed 24 hours later and the pancreas was weighed and harvested for subsequent myeloperoxidase (MPO) assay and histopathological analysis. Blood was also collected for serum amylase measurement. Results: EtOH + POA caused statistically significant increases in serum amylase levels, pancreatic MPO levels, and histopathology (P < 0.050.001 vs vehicle controls); pancreatic edema was elevated but not significantly. Pretreatment of the wild type mice 30 min before EtOH + POA injection with the TRPV1 antagonist drug, AMG9810, at a dose of 30 mg/kg ip resulted in reductions in serum amylase levels (89 ± 11%; P < 0.05), pancreatic edema (21 ± 20%), pancreatic MPO levels (58 ± 25%), and histopathology (78 ± 13%; P < 0.001) vs EtOH + POA alone. Similarly, EtOH + POA
New onset diabetes mellitus or
Su1245 Spectrum of use and Perceived Effectiveness of Endoscopic and Surgical Therapies for Chronic Pancreatitis in the United States Lisa M. Glass, Dhiraj Yadav, Elizabeth Kennard, Joseph Romagnuolo, Michelle A. Anderson, David C. Whitcomb, Timothy B. Gardner BACKGROUND & AIMS: Effectiveness of endoscopic and surgical therapies for treating chronic pancreatitis (CP) in the United States has been limited to small studies of selected patients. We aimed to describe the frequency of use and perceived effectiveness of endoscopic and surgical therapies in adult patients with CP treated at US referral centers. METHODS:
S-459
AGA Abstracts
AGA Abstracts
infusions every 2-3 months for two years. Medical records were reviewed and patients interviewed for follow-up. Data were abstracted on patient demographics, indications for RTX therapy and evidence of symptomatic, biochemical and radiographic disease response and relapse, if any. Results: Eleven male patients (mean age 66 years, 64% IgG4 seropositive) were treated with RTX. The disease indications for RTX treatment were IgG4-related sclerosing cholangitis (n=6), autoimmune pancreatitis (diffuse enlargement or focal mass) (n=5), and other organ involvement (n=2). Indications for use of RTX were relapse on immunomodulator (n=5), prednisone intolerance (n=4), or relapse on prednisone (n=2). Initiation of RTX began a median of 22 months following initial diagnosis of IgG4-RD, and patients were followed for a median of 6 months (0-60 months) after their first infusion. Each of the 10 patients who have completed the 4 dose induction regimen demonstrated either a partial or complete biochemical and/or radiographic response. In patients with abnormal liver tests prior to starting rituximab (n=5), normalization of tests was documented at a median 2.8 months from the initial infusion. Radiographic response was documented at a median 4.4 months (2.3-9.9 months). Remission was achieved without the use of concomitant steroids in 8 patients. One patient experienced a subsequent relapse >2 years after completing the RTX protocol. One patient developed neutropenia after 4 doses, and one patient developed interstitial lung infiltrates that are potentially attributable to RTX. Conclusions: Rituximab monotherapy can induce remission in IgG4-RD, even in those patients who are refractory or intolerant to either steroids or immunomodulators. Biochemical and radiographic responses are usually seen within 3-4 months. Treatment is well-tolerated and relapses are not seen while on treatment.