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Tu1289 The Long-Term Impact of Autoimmune Pancreatitis: Treatment Outcome, Survival, Pancreatic Function, and Quality of Life
AGA Abstracts
gold standard. AIMS AND OBJECTIVES: 1. To determine the frequency of small intestinal bacterial overgrowth in chronic pancreatitis. 2. To evaluate the sensitivity and specificity of Glucose Hydrogen Breath Test in SIBO (Small intestinal bacterial overgrowth) by comparing it with jejunal aspirate culture (Gold standard). MATERIAL AND METHODS: The study was an observational, cross sectional, prospective and a pilot study. Consecutive patients who were diagnosed with chronic pancreatitis in a tertiary care hospital from August 2011 to December 2012, were recruited . The patients between age of 18-60 years and diagnosed with chronic pancreatitis were included. The patients were excluded if received an oral antibiotic treatment in last 3 months, had taken proton pump inhibitors in last 1 week, received pancreatic enzyme supplements in last 2 weeks,had undergone any upper abdominal surgery, received radiation to the bowel, with small bowel diverticulosis or were pregnant . All the patients underwent a glucose hydrogen breath test(Bedfont, UK) and a jejunal aspirate in addition to the routine testing after obtaining a valid consent. The jejunal aspirate was cultured and colony forming units were estimated. The diagnosis of small intestinal bacterial overgrowth was made if the colony count was more than 105 colonies/ ml of aspirate or if the baseline breath hydrogen level was more than 20 ppm (parts per million) and/or more than 12 ppm was above the baseline. RESULTS: The flow of the patients is shown in figure 1 and the results in figure 2. A total of 48 patients were recruited for the study, 34 patients were males and 14 were females. The etiology of chronic pancreatitis in majority could not be established. The jejunal aspirate culture was positive in 16 and the breath test was positive in 12 patients with 2 cases as false positive. Hence the sensitivity and specificity of glucose hydrogen breath test was 62% and 92% respectively. CONCLUSIONS: 1. Small intestinal bacterial overgrowth is not uncommon in chronic pancreatitis, it was seen in one third of patients with chronic pancreatitis. 2. Glucose hydrogen breath test can be used for diagnosis of SIBO with moderate sensitivity and high specificity.
assessed prospectively. In addition, survival and cancer free survival were compared to an age and sex matched Dutch reference population. Results: Hundred-and-seven patients were included (87% male, 90% type 1; median age 71 yrs; IQR 61-78), with a median follow-up of 82 months (IQR 52-118). Thirty-four patients had undergone surgery for suspected pancreatic cancer (33%). Eighty-nine patients were (successfully) treated with steroids (83%). Fifty-five experienced a relapse (52%), for which IgG4-associated cholangitis was the sole risk factor (OR 5.3; 95% CI 2.3-12.4). At time of inclusion, 18 patients had died (17%), seven were lost to follow-up (7%), and 14 refused to supply prospective data (13%). Five deaths were attributable to IgG4-related disease (5%) and no pancreatic carcinoma was observed. Prospective data were obtained from 68 patients (64%). After a median of 75 months (IQR 50-106), 31 still required active AIP treatment (46%). Exocrine insufficiency was present in 82% of patients, with older age as a risk factor (OR: 1.07, 95% CI: 1.02-1.12). Endocrine insufficiency was found in 67% of patients, with older age and longer follow-up as risk factors (1.06 (95% CI: 1.02-1.11); OR: 1.03 (95% CI: 1.01-1.05)). The QoL of AIP patients was not impaired and there was no significant difference in survival (or cancer free survival), when compared to the reference population. Conclusion: Despite an excellent initial treatment response, recurrences were common in the longer term and almost half of AIP patients required maintenance therapy. Most patients became exo- and endocrine insufficient. However, their QoL was not impaired. Pancreatic cancer was not observed, and overall mortality and cancer risk were not increased. Tu1290 Long-Term Relapse Rates of Type 1 and 2 Autoimmune Pancreatitis Jorie Buijs, Djuna L. Cahen, Marianne J. Van Heerde, Erik Rauws, Lucas Maillette de Buy Wenniger, Bettina E. Hansen, Katharina Biermann, Joanne Verheij, Frank P. Vleggaar, Menno A. Brink, Ulrich Beuers, Henk R. van Buuren, Marco J. Bruno
Tu1288
Introduction: Autoimmune pancreatitis (AIP) is a distinct type of chronic pancreatitis, which responds dramatically to steroid therapy. Two subtypes are described: type 1 and 2, with type 2 being more rare, not IgG4 related, and less likely to relapse. However, little is known about differences in the long-term disease course between the two types. Therefore, we compared the clinical profile and long-term outcomes of type 1 and type 2 AIP. Methods: From our AIP database registry, we included patients with a minimum follow-up of 2 years. Type 1 AIP patients fulfilled either the HISORt criteria or the ICDC. Patients with type 2 AIP (either definite or probable) were diagnosed as proposed by Maire et al. (Am J Gastroenterol 2011;106:151-6). Information was subtracted from the database regarding baseline characteristics, (treatment) response, and relapses. Potential risk factors for relapse were evaluated; age, gender, AIP type, other organ involvement, serum IgG4 levels, steroid dose, and pancreatic surgery. Results: Hundred-and-seven patients were included (90% type 1; 87% male, median age 71 years), with a median follow-up of 82 months (IQR 52-118). At presentation, patients with type 1 AIP were older (63 years (IQR 53-70), versus 42 (IQR 27-52) in type 2; p<0.001) and had a higher male predominance (90%, versus 64% in type 2; p=0.036). Eighty-nine patients were treated with steroids (83%), with a 100% initial success rate. Overall, 55 patients experienced a relapse (52%). The first relapse occurred a median of 31 months (IQR 11-85) after diagnosis and most frequently involved the pancreas (51%) or biliary tract (62%). Furthermore, almost 80% of the relapses occurred within 2 years after diagnosis. Relapses were observed more frequently in type 1 patients (55%, versus 27% in type 2), but this difference did not reach statistical significance (p=0.11). Of note, type 2 patients never relapsed more than once. The only risk factor for relapse was the presence of IgG4-associated cholangitis (OR 5.3; 95% CI 2.3-12.4). Relapses occurred most often in unrecognized and therefore untreated patients (60%), or following the first two months of steroid cessation (31%). Subsequently, in 27% of these patients, azathioprine was added as maintenance therapy. Conclusion: In this large cohort of AIP patients, relapses were common for both disease types and typically occurred in the first 2 years after diagnosis. Although clinical profiles of type 1 and 2 AIP are distinct, we found no significant differences in relapse rates. Therefore, clinicians should observe all AIP patients carefully in the first years after tapering steroids.
Methionine Containing Antioxidants for Pain in Chronic Pancreatitis: A Systematic Review and Metaanalysis Rupjyoti Talukdar, Vivekananda Murthy, Nageshwar D. Reddy Background: Pain is the most compelling symptom of chronic pancreatitis (CP) that brings patients to medical attention. Pain mechanisms in CP include pancreatic nociception, neuropathy and neuroplasticity; which are triggered by ductal hypertension and recurrent acinar/ pancreatic inflammation. These mechanisms are substantially associated with oxidative stress, which is marked by depletion of methionine, among other antioxidant defenses. Methionine is important since it maintains the transsulfuration pathway in acinar cells thereby protecting the pancreas from repeated oxidative injury. Therefore, inclusion of methionine in antioxidant treatment for CP appears justified. However, clinical trials that used methionine-containing antioxidant for pain management have shown variable results. We performed a systematic review and metaanalysis of these clinical trials. Patient and methods: A literature search was conducted in Medline/Pubmed, EMBASE, Cochrane and Scopus databases; as well as in the proceedings of major gastroenterology meetings. The systematic review and metaanalysis was performed according to the PRISMA guidelines. The primary study outcome was pain relief. Two investigators reviewed studies independently and quality assessment was performed using Jadad score. Study heterogeneity was assessed by the Q measure for statistical significance and I2 measure for the amount of heterogeneity. Random effect model (DerSimonian and Laird) was used when there was heterogeneity. Eggers test was used to evaluate publication bias. Comprehensive Metaanalysis package was used for statistical analysis. Results: Five randomized studies in English language involving 345 patients were identified that used methionine-containing antioxidants. The study duration ranged from 10 weeks to 6 months. Four studies had a high quality with Jadad score of 5 out of 5. All five studies used methionine, organic selenium, ascorbate, beta-carotene and alpha-tocoferol; and compared with placebo. There was significant heterogeneity among studies (Tau20.634; Q- 17.9 [p=0.001] and I2- 88.8%). Three studies that reported a change in pain scores as an outcome were metaanalyzed. Based on random effects model (shown in Figure), the overall effect [standardized difference in means (95% CI)] in pain score reduction by methionine containing antioxidants was -0.96 (-1.92 to -0.00) [z= -1.96; p=0.05). The fourth study did not measure reduction in pain scores, but looked at number of painful days, which was significantly lower in patients taking antioxidants. The fifth study did not report change in pain score or other pain parameters as planned since there were discrepancies in filling the pain diaries. Conclusion: Methionine containing antioxidants appear to result in significant reduction of pain in CP. Further randomized controlled trials with homogeneous outcome measures are needed.
Tu1291 Clinicopathologic Correlation in Patients With Chronic Pancreatitis Undergoing Total Pancreatectomy Elham Afghani, Amitasha Sinha, Michael Cruise, Atif Zaheer, Mahya Faghih, Martin A. Makary, Kenzo Hirose, Marcia I. Canto, Mouen Khashab, Anne Marie Lennon, Vikesh K. Singh Background: Fibrosis on histology is considered the gold standard for diagnosing chronic pancreatitis (CP). However, there are few studies that have evaluated clinical history, magnetic resonance imaging (MRI), endoscopic ultrasound (EUS), & pancreatic function testing (PFT) with histology in patients with CP who have undergone a total pancreatectomy (TP). Aims: To evaluate the association between history of acute recurrent pancreatitis (ARP), MRI, EUS, & PFT with degree of fibrosis in patients with CP who have undergone TP. Methods: All consecutive adult patients with intractable chronic pancreatic type abdominal pain (age≥18 yrs) who underwent preoperative MRI, EUS, & PFT followed by TP from 8/11 to 10/13 were included. ARP was defined as ≥2 documented episodes of acute pancreatitis (AP). An abnormal MRI was defined by presence of T1 signal intensity loss & evaluated by a radiologist blinded to clinical data. EUS criteria were defined by 5 ductal & parenchymal features. All EUS images were reviewed & scored by 2 endosonographers independently. Abnormal PFT was defined by fecal elastase <200 μg/dL, serum trypsin <19 ng/dL, and/or secretin stimulated 1 hr bicarbonate concentration ≤ 80mEq/L. Surgical wedge biopsies were obtained from head & body/tail during TP. Histology was evaluated by pathologist blinded to results of all preoperative testing. Perilobular & intralobular fibrosis scores for each wedge biopsy specimen were calculated & averaged. Mild fibrosis was defined as fibrosis score (FS) of 0-6 & severe fibrosis as FS of 7-12. ARP, T1 signal loss, EUS criteria ≥6, & abnormal PFT was correlated with fibrosis on histology. Chi-squared testing & logistic regression was used for univariable and multivariable analysis, respectively. The association between severe fibrosis and the number of AP was assessed using the Cochrane test for trend. Results: There were 30 patients (66.7% females, mean age 44 years, 73.3% ARP, 61.5% T1 signal loss,
Tu1289 The Long-Term Impact of Autoimmune Pancreatitis: Treatment Outcome, Survival, Pancreatic Function, and Quality of Life Jorie Buijs, Djuna L. Cahen, Marianne J. Van Heerde, Erik Rauws, Lucas Maillette de Buy Wenniger, Bettina E. Hansen, Katharina Biermann, Joanne Verheij, Frank P. Vleggaar, Menno A. Brink, Ulrich Beuers, Henk R. van Buuren, Marco J. Bruno Introduction: Autoimmune pancreatitis (AIP) is a distinct type of pancreatitis, usually observed as part of a systemic IgG4-related disease. The differential diagnosis is challenging, as symptoms may mimic those of pancreatic cancer. The long-term disease course is scarcely described. Methods: From our AIP database registry, we included patients with a minimum follow-up of 2 years. Information was subtracted regarding (treatment) outcome and relapses. After informed consent was obtained, pancreatic function and quality of life (QoL) were
AGA Abstracts
S-804
gold standard. AIMS AND OBJECTIVES: 1. To determine the frequency of small intestinal bacterial overgrowth in chronic pancreatitis. 2. To evaluate the sensitivity and specificity of Glucose Hydrogen Breath Test in SIBO (Small intestinal bacterial overgrowth) by comparing it with jejunal aspirate culture (Gold standard). MATERIAL AND METHODS: The study was an observational, cross sectional, prospective and a pilot study. Consecutive patients who were diagnosed with chronic pancreatitis in a tertiary care hospital from August 2011 to December 2012, were recruited . The patients between age of 18-60 years and diagnosed with chronic pancreatitis were included. The patients were excluded if received an oral antibiotic treatment in last 3 months, had taken proton pump inhibitors in last 1 week, received pancreatic enzyme supplements in last 2 weeks,had undergone any upper abdominal surgery, received radiation to the bowel, with small bowel diverticulosis or were pregnant . All the patients underwent a glucose hydrogen breath test(Bedfont, UK) and a jejunal aspirate in addition to the routine testing after obtaining a valid consent. The jejunal aspirate was cultured and colony forming units were estimated. The diagnosis of small intestinal bacterial overgrowth was made if the colony count was more than 105 colonies/ ml of aspirate or if the baseline breath hydrogen level was more than 20 ppm (parts per million) and/or more than 12 ppm was above the baseline. RESULTS: The flow of the patients is shown in figure 1 and the results in figure 2. A total of 48 patients were recruited for the study, 34 patients were males and 14 were females. The etiology of chronic pancreatitis in majority could not be established. The jejunal aspirate culture was positive in 16 and the breath test was positive in 12 patients with 2 cases as false positive. Hence the sensitivity and specificity of glucose hydrogen breath test was 62% and 92% respectively. CONCLUSIONS: 1. Small intestinal bacterial overgrowth is not uncommon in chronic pancreatitis, it was seen in one third of patients with chronic pancreatitis. 2. Glucose hydrogen breath test can be used for diagnosis of SIBO with moderate sensitivity and high specificity.
assessed prospectively. In addition, survival and cancer free survival were compared to an age and sex matched Dutch reference population. Results: Hundred-and-seven patients were included (87% male, 90% type 1; median age 71 yrs; IQR 61-78), with a median follow-up of 82 months (IQR 52-118). Thirty-four patients had undergone surgery for suspected pancreatic cancer (33%). Eighty-nine patients were (successfully) treated with steroids (83%). Fifty-five experienced a relapse (52%), for which IgG4-associated cholangitis was the sole risk factor (OR 5.3; 95% CI 2.3-12.4). At time of inclusion, 18 patients had died (17%), seven were lost to follow-up (7%), and 14 refused to supply prospective data (13%). Five deaths were attributable to IgG4-related disease (5%) and no pancreatic carcinoma was observed. Prospective data were obtained from 68 patients (64%). After a median of 75 months (IQR 50-106), 31 still required active AIP treatment (46%). Exocrine insufficiency was present in 82% of patients, with older age as a risk factor (OR: 1.07, 95% CI: 1.02-1.12). Endocrine insufficiency was found in 67% of patients, with older age and longer follow-up as risk factors (1.06 (95% CI: 1.02-1.11); OR: 1.03 (95% CI: 1.01-1.05)). The QoL of AIP patients was not impaired and there was no significant difference in survival (or cancer free survival), when compared to the reference population. Conclusion: Despite an excellent initial treatment response, recurrences were common in the longer term and almost half of AIP patients required maintenance therapy. Most patients became exo- and endocrine insufficient. However, their QoL was not impaired. Pancreatic cancer was not observed, and overall mortality and cancer risk were not increased. Tu1290 Long-Term Relapse Rates of Type 1 and 2 Autoimmune Pancreatitis Jorie Buijs, Djuna L. Cahen, Marianne J. Van Heerde, Erik Rauws, Lucas Maillette de Buy Wenniger, Bettina E. Hansen, Katharina Biermann, Joanne Verheij, Frank P. Vleggaar, Menno A. Brink, Ulrich Beuers, Henk R. van Buuren, Marco J. Bruno
Tu1288
Introduction: Autoimmune pancreatitis (AIP) is a distinct type of chronic pancreatitis, which responds dramatically to steroid therapy. Two subtypes are described: type 1 and 2, with type 2 being more rare, not IgG4 related, and less likely to relapse. However, little is known about differences in the long-term disease course between the two types. Therefore, we compared the clinical profile and long-term outcomes of type 1 and type 2 AIP. Methods: From our AIP database registry, we included patients with a minimum follow-up of 2 years. Type 1 AIP patients fulfilled either the HISORt criteria or the ICDC. Patients with type 2 AIP (either definite or probable) were diagnosed as proposed by Maire et al. (Am J Gastroenterol 2011;106:151-6). Information was subtracted from the database regarding baseline characteristics, (treatment) response, and relapses. Potential risk factors for relapse were evaluated; age, gender, AIP type, other organ involvement, serum IgG4 levels, steroid dose, and pancreatic surgery. Results: Hundred-and-seven patients were included (90% type 1; 87% male, median age 71 years), with a median follow-up of 82 months (IQR 52-118). At presentation, patients with type 1 AIP were older (63 years (IQR 53-70), versus 42 (IQR 27-52) in type 2; p<0.001) and had a higher male predominance (90%, versus 64% in type 2; p=0.036). Eighty-nine patients were treated with steroids (83%), with a 100% initial success rate. Overall, 55 patients experienced a relapse (52%). The first relapse occurred a median of 31 months (IQR 11-85) after diagnosis and most frequently involved the pancreas (51%) or biliary tract (62%). Furthermore, almost 80% of the relapses occurred within 2 years after diagnosis. Relapses were observed more frequently in type 1 patients (55%, versus 27% in type 2), but this difference did not reach statistical significance (p=0.11). Of note, type 2 patients never relapsed more than once. The only risk factor for relapse was the presence of IgG4-associated cholangitis (OR 5.3; 95% CI 2.3-12.4). Relapses occurred most often in unrecognized and therefore untreated patients (60%), or following the first two months of steroid cessation (31%). Subsequently, in 27% of these patients, azathioprine was added as maintenance therapy. Conclusion: In this large cohort of AIP patients, relapses were common for both disease types and typically occurred in the first 2 years after diagnosis. Although clinical profiles of type 1 and 2 AIP are distinct, we found no significant differences in relapse rates. Therefore, clinicians should observe all AIP patients carefully in the first years after tapering steroids.
Methionine Containing Antioxidants for Pain in Chronic Pancreatitis: A Systematic Review and Metaanalysis Rupjyoti Talukdar, Vivekananda Murthy, Nageshwar D. Reddy Background: Pain is the most compelling symptom of chronic pancreatitis (CP) that brings patients to medical attention. Pain mechanisms in CP include pancreatic nociception, neuropathy and neuroplasticity; which are triggered by ductal hypertension and recurrent acinar/ pancreatic inflammation. These mechanisms are substantially associated with oxidative stress, which is marked by depletion of methionine, among other antioxidant defenses. Methionine is important since it maintains the transsulfuration pathway in acinar cells thereby protecting the pancreas from repeated oxidative injury. Therefore, inclusion of methionine in antioxidant treatment for CP appears justified. However, clinical trials that used methionine-containing antioxidant for pain management have shown variable results. We performed a systematic review and metaanalysis of these clinical trials. Patient and methods: A literature search was conducted in Medline/Pubmed, EMBASE, Cochrane and Scopus databases; as well as in the proceedings of major gastroenterology meetings. The systematic review and metaanalysis was performed according to the PRISMA guidelines. The primary study outcome was pain relief. Two investigators reviewed studies independently and quality assessment was performed using Jadad score. Study heterogeneity was assessed by the Q measure for statistical significance and I2 measure for the amount of heterogeneity. Random effect model (DerSimonian and Laird) was used when there was heterogeneity. Eggers test was used to evaluate publication bias. Comprehensive Metaanalysis package was used for statistical analysis. Results: Five randomized studies in English language involving 345 patients were identified that used methionine-containing antioxidants. The study duration ranged from 10 weeks to 6 months. Four studies had a high quality with Jadad score of 5 out of 5. All five studies used methionine, organic selenium, ascorbate, beta-carotene and alpha-tocoferol; and compared with placebo. There was significant heterogeneity among studies (Tau20.634; Q- 17.9 [p=0.001] and I2- 88.8%). Three studies that reported a change in pain scores as an outcome were metaanalyzed. Based on random effects model (shown in Figure), the overall effect [standardized difference in means (95% CI)] in pain score reduction by methionine containing antioxidants was -0.96 (-1.92 to -0.00) [z= -1.96; p=0.05). The fourth study did not measure reduction in pain scores, but looked at number of painful days, which was significantly lower in patients taking antioxidants. The fifth study did not report change in pain score or other pain parameters as planned since there were discrepancies in filling the pain diaries. Conclusion: Methionine containing antioxidants appear to result in significant reduction of pain in CP. Further randomized controlled trials with homogeneous outcome measures are needed.
Tu1291 Clinicopathologic Correlation in Patients With Chronic Pancreatitis Undergoing Total Pancreatectomy Elham Afghani, Amitasha Sinha, Michael Cruise, Atif Zaheer, Mahya Faghih, Martin A. Makary, Kenzo Hirose, Marcia I. Canto, Mouen Khashab, Anne Marie Lennon, Vikesh K. Singh Background: Fibrosis on histology is considered the gold standard for diagnosing chronic pancreatitis (CP). However, there are few studies that have evaluated clinical history, magnetic resonance imaging (MRI), endoscopic ultrasound (EUS), & pancreatic function testing (PFT) with histology in patients with CP who have undergone a total pancreatectomy (TP). Aims: To evaluate the association between history of acute recurrent pancreatitis (ARP), MRI, EUS, & PFT with degree of fibrosis in patients with CP who have undergone TP. Methods: All consecutive adult patients with intractable chronic pancreatic type abdominal pain (age≥18 yrs) who underwent preoperative MRI, EUS, & PFT followed by TP from 8/11 to 10/13 were included. ARP was defined as ≥2 documented episodes of acute pancreatitis (AP). An abnormal MRI was defined by presence of T1 signal intensity loss & evaluated by a radiologist blinded to clinical data. EUS criteria were defined by 5 ductal & parenchymal features. All EUS images were reviewed & scored by 2 endosonographers independently. Abnormal PFT was defined by fecal elastase <200 μg/dL, serum trypsin <19 ng/dL, and/or secretin stimulated 1 hr bicarbonate concentration ≤ 80mEq/L. Surgical wedge biopsies were obtained from head & body/tail during TP. Histology was evaluated by pathologist blinded to results of all preoperative testing. Perilobular & intralobular fibrosis scores for each wedge biopsy specimen were calculated & averaged. Mild fibrosis was defined as fibrosis score (FS) of 0-6 & severe fibrosis as FS of 7-12. ARP, T1 signal loss, EUS criteria ≥6, & abnormal PFT was correlated with fibrosis on histology. Chi-squared testing & logistic regression was used for univariable and multivariable analysis, respectively. The association between severe fibrosis and the number of AP was assessed using the Cochrane test for trend. Results: There were 30 patients (66.7% females, mean age 44 years, 73.3% ARP, 61.5% T1 signal loss,
Tu1289 The Long-Term Impact of Autoimmune Pancreatitis: Treatment Outcome, Survival, Pancreatic Function, and Quality of Life Jorie Buijs, Djuna L. Cahen, Marianne J. Van Heerde, Erik Rauws, Lucas Maillette de Buy Wenniger, Bettina E. Hansen, Katharina Biermann, Joanne Verheij, Frank P. Vleggaar, Menno A. Brink, Ulrich Beuers, Henk R. van Buuren, Marco J. Bruno Introduction: Autoimmune pancreatitis (AIP) is a distinct type of pancreatitis, usually observed as part of a systemic IgG4-related disease. The differential diagnosis is challenging, as symptoms may mimic those of pancreatic cancer. The long-term disease course is scarcely described. Methods: From our AIP database registry, we included patients with a minimum follow-up of 2 years. Information was subtracted regarding (treatment) outcome and relapses. After informed consent was obtained, pancreatic function and quality of life (QoL) were
AGA Abstracts
S-804