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Pancreatic Head Mass in Chronic Pancreatitis is Inflammatory in Alcoholic Pancreatitis and Often Malignant in Idiopathic Chronic Pancreatitis
Tu1937
severity of pancreatitis attacks were in comparison to the latter group. Pain control was not succesfull with conventional medical therapy in two patients and EUS-guided celiac plexus block in one of them and operation in one other with partial response. Conclusion: We reported four young patients with pancreatic insufficiency who have no other etiological factor except from therapy resistant hyperlipidemia, we argue that HTG could be an etiological factor in some patients with CP. It appears in younger age and course of the disease is more severe. Taking into account the adverse effects of HTG and poorly controlled diabetes, it appears that this special subset of CP patients require more attention and more aggressive approaches in reference to a wholistic management.
AGA Abstracts
Investigation of Predictive Factors for Disease Progression or Relapse of Autoimmune Pancreatitis Shinsuke Koshita, Naotaka Fujita, Yutaka Noda, Go Kobayashi, Kei Ito, Takashi Obana, Jun Horaguchi, Yoshihide Kanno, Takahisa Ogawa Background: Some patients with autoimmune pancreatitis (AIP) suffer from disease progression during follow-up with no medication or from relapse after steroid treatment. Aim: To elucidate the proportion of patients with AIP showing disease progression or relapse and its predictive factors. Patients: Thirty-eight patients with AIP based on HISORt criteria from 1988 to 2010 were included in this study. Results: Of the 38 patients, 10 with histologically confirmed AIP after resection were followed-up conservatively with no medication. One patient (10%) developed relapse of AIP in the remnant pancreas. Of the other 28 patients, 14 were followed up without surgery or medication (median follow-up period: 1525 days), 2 of which (14.3%) showed disease progression and received steroid treatment. The remaining 14 patients received steroid treatment (initial dose: 30-60 mg/day) because of symptoms, and all of them achieved remission. In 7 of these 14 patients, steroid treatment was stopped (period to discontinuance of the treatment: 23-1366 days), and 4 of these 7 (57.1%) developed relapse (period to relapse: 19-737 days). The remaining 7 patients received maintenance treatment with low-dose steroid (period of maintenance treatment: 155-2749 days), 1 of which (14.3%) developed relapse after 265 days from initial steroid administration. Sex, age, diabetes mellitus (DM), icterus, serum IgG4 level, diffuse pancreatic swelling, other organ involvement (OOI), steroid treatment, and maintenance treatment with low-dose steroid were investigated with univariate analysis in 30 patients of AIP who had been followed up for more than 6 months to evaluate the predictive factors for disease progression or relapse, the results being as follows: male (p=0.623, OR: 1.1, 95%CI: 0.2-7.5), age less than 70 y.o. at onset (p=0.004), icterus (p=0.288, OR: 3.3, 95%CI: 0.3-32.3), DM (p=0.659, OR: 1.0, 95%CI: 0.2-5.0), serum IgG4 level >500 mg/dl (p=0.651, OR: 1.1, 95%CI: 0.28.1), diffuse pancreatic swelling (p=0.223, OR: 2.9, 95%CI: 0.5-16.4), OOI (p=0.541, OR: 1.4, 95%CI: 0.2-9.2), steroid treatment (p=0.195, OR: 2.9, 95%CI: 0.6-15.6) and maintenance treatment with low-dose steroid (p=0.480, OR: 2.1, 95%CI: 0.2-20.8). Multivariate analysis including age, diffuse pancreatic swelling and steroid treatment, which showed p<0.25 by univariate analysis, revealed that only age less than 70 y.o. at onset was a significant factor of disease progression or relapse (p=0.049). Conclusion: Disease progression or relapse was observed in 10% of resected cases, 14% of cases without medication, 57% of cases with discontinuance of steroid therapy after remission, and 14% of cases with low-dose steroid therapy. Age at onset ( less than 70 y.o. ) was considered as the predictive factor of disease progression or relapse of AIP.
Tu1940 Baseline Levels of Plasma Sonic Hedgehog Vary Widely but Are Reduced in Subjects With Pancreatic Cancer Mohamad El-Zaatari, Stephanie Daignault, Michelle A. Anderson, Caitlyn M. Plonka, Juanita L. Merchant Introduction: Prior studies have correlated the development of pancreatic cancer with re-expression of Sonic Hedgehog (Shh), normally expressed only during fetal pancreatic development. Indeed, overexpression of Shh occurs in early pancreatic intraepithelial neoplasia (PanIN) lesions, suggesting that Shh might be an early diagnostic marker for pancreatic cancer. We hypothesized that excessive Shh produced in pancreatic adenocarcinoma is secreted into the circulation. Therefore, to determine the levels of Shh in the plasma, we developed an ELISA for human Shh. Methods: Blood samples from 40 male and 40 female self-identified normal human subjects age 18 to 70 were collected over 1 year. In addition, age and gender-matched plasma samples were collected from 38 normal, 20 chronic pancreatitis, and 20 pancreatic cancer patients. All subjects provided written informed consent. The human Shh ELISA assay was developed by modifying the mouse-specific Shh DuoSet ELISA kit (R&D systems). Since the detection antibody in this kit only shows 10% cross-reactivity to human Shh, the detection antibody was substituted with goat polyclonal anti-Shh (N19, Santa Cruz) that detects both human and mouse Shh. The antibody was biotinylated using the Sulfo-NHS-LC-Biotin kit from Pierce, and the specificity validated by immunofluorescence and western blot using tissue from transgenic mice and human cell lines overexpressing Shh downstream the CMV-promoter. Results: The Shh N-19 antibody detected ectopic expression of Shh in transgenic mice and transfected NIH-3T3 cells but not in non-transgenic mice or vector control-transfected cells. Next, the biotinylated antibody was further validated on tissue sections from pCMV-Shh mice. Since plasma detection of Shh in human subjects has not been previously reported, we determined the range of the ELISA assay using recombinant human Shh peptide. The ELISA detected Shh in a concentration range between 2 and 2000 ng/ml. The bound antigen detected by ELISA was eluted from the plates then validated by western blot. We used the ELISA to determine plasma Shh levels in normal human samples, and found Shh levels to be highly variable among normal human subjects with a mean Shh of 138 ng/ml (S.D. = 412). Shh levels decreased with age (pearson correlation (r) = -0.19) but showed no gender difference. Surprisingly, the average levels were lower in pancreatitis (45ng/ml, S.D. = 98) and pancreatic cancer (17ng/ml, S.D. = 44) patients. Conclusion: Shh circulates in human blood plasma and serological levels can be detected by ELISA. The normal levels in humans vary widely, and are not gender dependent. Surprisingly, reduced levels (relative to normals and patients with chronic pancreatitis) are found in pancreatic cancer patients, but is not a significant predictor of pancreatic cancer.
Tu1938 Pancreatic Head Mass in Chronic Pancreatitis is Inflammatory in Alcoholic Pancreatitis and Often Malignant in Idiopathic Chronic Pancreatitis Shallu Midha, S. Shalimar, Ajay Kumar, Pramod K. Garg Background: Patients with chronic pancreatitis (CP) have an increased risk for pancreatic cancer. Pancreatic head mass in patients with chronic pancreatitis is a diagnostic dilemma with malignancy being a major concern. Objective: To determine the nature of pancreatic head mass in patients with CP. Methods: All consecutive patients with CP who were diagnosed to have additional pancreatic head mass on a computed tomography scan formed the study group. They were subjected to clinical evaluation and imaging studies including a PET-CT scan and endosonography (EUS). The diagnosis of malignancy versus inflammatory mass was confirmed on histo/cytopathology and clinical criteria. Patients were treated with a standard protocol. Patients were included after an informed written consent and institutional ethical clearance was obtained. Results: Of 402 patients with CP, 57 presented with a pancreatic head mass in addition to the features of CP. Their mean age was 44.5 years; 49 were males. The etiology of CP was alcohol in 29 (51%), idiopathic in 27 (47%) and hereditary in the remaining patient. Twenty nine of the 57 patients had associated biliary obstruction. Of the 57 patients with CP and a pancreatic head mass, 6 were found to have pancreatic cancer as the cause of pancreatic mass and 32 had an inflammatory mass. EUS ruled out any mass in 15 patients and 4 patients were lost to follow up. The mean age of the 6 patients with CP and malignancy was 47.5 years and the mean duration of CP in them was 13.93 years. Of these 6 patients with CP and malignancy, the etiology of CP was idiopathic in 5 and hereditary in 1 patient. All the 6 patients had pancreatic calcification and 5 had diabetes. Of the 29 patients with alcoholic CP, 26 had an inflammatory mass and no mass was confirmed in the remaining 3 patients. Of the 27 patients with idiopathic CP, 5 had malignancy, 3 had inflammatory mass, and no mass was confirmed in the remaining 19 patients. Conclusion: Pancreatic head mass was present in 28.5% of patients with CP and was inflammatory in nature in those with alcoholic CP; in contrast, it was often malignant in those with idiopathic CP.
Tu1941 Role of Sweat Testing in Patients With Idiopathic Pancreatitis Chee Y. Ooi, Annie Dupuis, Katherine Keenan, Elizabeth Tullis, Peter R. Durie Background and Aim: A diagnosis of cystic fibrosis (CF) could be made in 10% of idiopathic pancreatitis (PANC) patients on sweat testing and/or identification of CF-causing mutations on both alleles; the diagnosis may be equivocal in up to 20% of patients (Bishop 2005, Ooi 2010). Since sweat chloride results are traditionally interpreted categorically (normal <40mmol/L, borderline 40-59mmol/L or abnormal ≥60mmol/L), clinicians may face diagnostic uncertainty when results are borderline. The aim was to evaluate the performance of sweat chloride for diagnosing CF. Specifically we determined the performance of sweat testing in 2 clinical settings: (1) general population, and (2) tertiary referral to a Gastroenterology (GI)-CF clinic for PANC. Methods: Sweat chloride from healthy people (healthy controls [n=84], heterozygotes [n=48]) and patients with an established diagnosis (based on consensus criteria) of pancreatic sufficient (PS; n=64) and insufficient (PI; n=43) CF were ascertained to derive diagnostic performance parameters (sensitivity, specificity, positive predictive values [PV] and negative PV). Exocrine pancreatic function was defined based on objective functional testing. These parameters are dependent on type of patient population and disease incidence in each population; therefore, to calculate these parameters for each of the 2 clinical scenarios, the following evidence based assumptions were made: (1) general population - pre-test probability for CF is 1 in 3608, carrier rate is 4%, PI:PS CF ratio = 8:1, and (2) GI-CF clinic - pre-test probability for CF is 10%, carrier rate is 50%, all CF patients at risk of
Tu1939 Hypertriglyceridemia Could Be an Etiological Factor in Chronic Pancreatitis Gurhan Sisman, Hakan Senturk, Ibrahim Hatemi, Rana Senturk, Sebati Ozdemir Introduction: Hypertriglyceridemia(HTG)can induce recurrent acute pancreatitis but its role in the etiology of chronic pancreatitis(CP)is controversial. Material and methods: We retrospectively analysed the clinical, laboratory and radiolgical findings of 4 CP patients with significant HTG without any other etiology and compared their data to the findings of CP without HTG. These four patients have had multiple attacks of pancreatitis and radiological features of chronic pancreatitis at abdominal tomography scan and/or at endosonography(EUS). According to Rosemont classification EUS features were consistent in 3 and suggestive in 1 patient. In all other patients diagnosis was based on Rosemont classification as well. Results: The comparison of the HTG group with the other CP group is showed in the table. The mean triglyceride level was 1768±1442 mg/dl in the first group. All four were smokers and non-drinkers. Portal vein thrombosis was present in two and pseudocyst in other two. All were diabetic with poor glycemic control requing insulin therapy. The frequency and
AGA Abstracts
S-854
severity of pancreatitis attacks were in comparison to the latter group. Pain control was not succesfull with conventional medical therapy in two patients and EUS-guided celiac plexus block in one of them and operation in one other with partial response. Conclusion: We reported four young patients with pancreatic insufficiency who have no other etiological factor except from therapy resistant hyperlipidemia, we argue that HTG could be an etiological factor in some patients with CP. It appears in younger age and course of the disease is more severe. Taking into account the adverse effects of HTG and poorly controlled diabetes, it appears that this special subset of CP patients require more attention and more aggressive approaches in reference to a wholistic management.
AGA Abstracts
Investigation of Predictive Factors for Disease Progression or Relapse of Autoimmune Pancreatitis Shinsuke Koshita, Naotaka Fujita, Yutaka Noda, Go Kobayashi, Kei Ito, Takashi Obana, Jun Horaguchi, Yoshihide Kanno, Takahisa Ogawa Background: Some patients with autoimmune pancreatitis (AIP) suffer from disease progression during follow-up with no medication or from relapse after steroid treatment. Aim: To elucidate the proportion of patients with AIP showing disease progression or relapse and its predictive factors. Patients: Thirty-eight patients with AIP based on HISORt criteria from 1988 to 2010 were included in this study. Results: Of the 38 patients, 10 with histologically confirmed AIP after resection were followed-up conservatively with no medication. One patient (10%) developed relapse of AIP in the remnant pancreas. Of the other 28 patients, 14 were followed up without surgery or medication (median follow-up period: 1525 days), 2 of which (14.3%) showed disease progression and received steroid treatment. The remaining 14 patients received steroid treatment (initial dose: 30-60 mg/day) because of symptoms, and all of them achieved remission. In 7 of these 14 patients, steroid treatment was stopped (period to discontinuance of the treatment: 23-1366 days), and 4 of these 7 (57.1%) developed relapse (period to relapse: 19-737 days). The remaining 7 patients received maintenance treatment with low-dose steroid (period of maintenance treatment: 155-2749 days), 1 of which (14.3%) developed relapse after 265 days from initial steroid administration. Sex, age, diabetes mellitus (DM), icterus, serum IgG4 level, diffuse pancreatic swelling, other organ involvement (OOI), steroid treatment, and maintenance treatment with low-dose steroid were investigated with univariate analysis in 30 patients of AIP who had been followed up for more than 6 months to evaluate the predictive factors for disease progression or relapse, the results being as follows: male (p=0.623, OR: 1.1, 95%CI: 0.2-7.5), age less than 70 y.o. at onset (p=0.004), icterus (p=0.288, OR: 3.3, 95%CI: 0.3-32.3), DM (p=0.659, OR: 1.0, 95%CI: 0.2-5.0), serum IgG4 level >500 mg/dl (p=0.651, OR: 1.1, 95%CI: 0.28.1), diffuse pancreatic swelling (p=0.223, OR: 2.9, 95%CI: 0.5-16.4), OOI (p=0.541, OR: 1.4, 95%CI: 0.2-9.2), steroid treatment (p=0.195, OR: 2.9, 95%CI: 0.6-15.6) and maintenance treatment with low-dose steroid (p=0.480, OR: 2.1, 95%CI: 0.2-20.8). Multivariate analysis including age, diffuse pancreatic swelling and steroid treatment, which showed p<0.25 by univariate analysis, revealed that only age less than 70 y.o. at onset was a significant factor of disease progression or relapse (p=0.049). Conclusion: Disease progression or relapse was observed in 10% of resected cases, 14% of cases without medication, 57% of cases with discontinuance of steroid therapy after remission, and 14% of cases with low-dose steroid therapy. Age at onset ( less than 70 y.o. ) was considered as the predictive factor of disease progression or relapse of AIP.
Tu1940 Baseline Levels of Plasma Sonic Hedgehog Vary Widely but Are Reduced in Subjects With Pancreatic Cancer Mohamad El-Zaatari, Stephanie Daignault, Michelle A. Anderson, Caitlyn M. Plonka, Juanita L. Merchant Introduction: Prior studies have correlated the development of pancreatic cancer with re-expression of Sonic Hedgehog (Shh), normally expressed only during fetal pancreatic development. Indeed, overexpression of Shh occurs in early pancreatic intraepithelial neoplasia (PanIN) lesions, suggesting that Shh might be an early diagnostic marker for pancreatic cancer. We hypothesized that excessive Shh produced in pancreatic adenocarcinoma is secreted into the circulation. Therefore, to determine the levels of Shh in the plasma, we developed an ELISA for human Shh. Methods: Blood samples from 40 male and 40 female self-identified normal human subjects age 18 to 70 were collected over 1 year. In addition, age and gender-matched plasma samples were collected from 38 normal, 20 chronic pancreatitis, and 20 pancreatic cancer patients. All subjects provided written informed consent. The human Shh ELISA assay was developed by modifying the mouse-specific Shh DuoSet ELISA kit (R&D systems). Since the detection antibody in this kit only shows 10% cross-reactivity to human Shh, the detection antibody was substituted with goat polyclonal anti-Shh (N19, Santa Cruz) that detects both human and mouse Shh. The antibody was biotinylated using the Sulfo-NHS-LC-Biotin kit from Pierce, and the specificity validated by immunofluorescence and western blot using tissue from transgenic mice and human cell lines overexpressing Shh downstream the CMV-promoter. Results: The Shh N-19 antibody detected ectopic expression of Shh in transgenic mice and transfected NIH-3T3 cells but not in non-transgenic mice or vector control-transfected cells. Next, the biotinylated antibody was further validated on tissue sections from pCMV-Shh mice. Since plasma detection of Shh in human subjects has not been previously reported, we determined the range of the ELISA assay using recombinant human Shh peptide. The ELISA detected Shh in a concentration range between 2 and 2000 ng/ml. The bound antigen detected by ELISA was eluted from the plates then validated by western blot. We used the ELISA to determine plasma Shh levels in normal human samples, and found Shh levels to be highly variable among normal human subjects with a mean Shh of 138 ng/ml (S.D. = 412). Shh levels decreased with age (pearson correlation (r) = -0.19) but showed no gender difference. Surprisingly, the average levels were lower in pancreatitis (45ng/ml, S.D. = 98) and pancreatic cancer (17ng/ml, S.D. = 44) patients. Conclusion: Shh circulates in human blood plasma and serological levels can be detected by ELISA. The normal levels in humans vary widely, and are not gender dependent. Surprisingly, reduced levels (relative to normals and patients with chronic pancreatitis) are found in pancreatic cancer patients, but is not a significant predictor of pancreatic cancer.
Tu1938 Pancreatic Head Mass in Chronic Pancreatitis is Inflammatory in Alcoholic Pancreatitis and Often Malignant in Idiopathic Chronic Pancreatitis Shallu Midha, S. Shalimar, Ajay Kumar, Pramod K. Garg Background: Patients with chronic pancreatitis (CP) have an increased risk for pancreatic cancer. Pancreatic head mass in patients with chronic pancreatitis is a diagnostic dilemma with malignancy being a major concern. Objective: To determine the nature of pancreatic head mass in patients with CP. Methods: All consecutive patients with CP who were diagnosed to have additional pancreatic head mass on a computed tomography scan formed the study group. They were subjected to clinical evaluation and imaging studies including a PET-CT scan and endosonography (EUS). The diagnosis of malignancy versus inflammatory mass was confirmed on histo/cytopathology and clinical criteria. Patients were treated with a standard protocol. Patients were included after an informed written consent and institutional ethical clearance was obtained. Results: Of 402 patients with CP, 57 presented with a pancreatic head mass in addition to the features of CP. Their mean age was 44.5 years; 49 were males. The etiology of CP was alcohol in 29 (51%), idiopathic in 27 (47%) and hereditary in the remaining patient. Twenty nine of the 57 patients had associated biliary obstruction. Of the 57 patients with CP and a pancreatic head mass, 6 were found to have pancreatic cancer as the cause of pancreatic mass and 32 had an inflammatory mass. EUS ruled out any mass in 15 patients and 4 patients were lost to follow up. The mean age of the 6 patients with CP and malignancy was 47.5 years and the mean duration of CP in them was 13.93 years. Of these 6 patients with CP and malignancy, the etiology of CP was idiopathic in 5 and hereditary in 1 patient. All the 6 patients had pancreatic calcification and 5 had diabetes. Of the 29 patients with alcoholic CP, 26 had an inflammatory mass and no mass was confirmed in the remaining 3 patients. Of the 27 patients with idiopathic CP, 5 had malignancy, 3 had inflammatory mass, and no mass was confirmed in the remaining 19 patients. Conclusion: Pancreatic head mass was present in 28.5% of patients with CP and was inflammatory in nature in those with alcoholic CP; in contrast, it was often malignant in those with idiopathic CP.
Tu1941 Role of Sweat Testing in Patients With Idiopathic Pancreatitis Chee Y. Ooi, Annie Dupuis, Katherine Keenan, Elizabeth Tullis, Peter R. Durie Background and Aim: A diagnosis of cystic fibrosis (CF) could be made in 10% of idiopathic pancreatitis (PANC) patients on sweat testing and/or identification of CF-causing mutations on both alleles; the diagnosis may be equivocal in up to 20% of patients (Bishop 2005, Ooi 2010). Since sweat chloride results are traditionally interpreted categorically (normal <40mmol/L, borderline 40-59mmol/L or abnormal ≥60mmol/L), clinicians may face diagnostic uncertainty when results are borderline. The aim was to evaluate the performance of sweat chloride for diagnosing CF. Specifically we determined the performance of sweat testing in 2 clinical settings: (1) general population, and (2) tertiary referral to a Gastroenterology (GI)-CF clinic for PANC. Methods: Sweat chloride from healthy people (healthy controls [n=84], heterozygotes [n=48]) and patients with an established diagnosis (based on consensus criteria) of pancreatic sufficient (PS; n=64) and insufficient (PI; n=43) CF were ascertained to derive diagnostic performance parameters (sensitivity, specificity, positive predictive values [PV] and negative PV). Exocrine pancreatic function was defined based on objective functional testing. These parameters are dependent on type of patient population and disease incidence in each population; therefore, to calculate these parameters for each of the 2 clinical scenarios, the following evidence based assumptions were made: (1) general population - pre-test probability for CF is 1 in 3608, carrier rate is 4%, PI:PS CF ratio = 8:1, and (2) GI-CF clinic - pre-test probability for CF is 10%, carrier rate is 50%, all CF patients at risk of
Tu1939 Hypertriglyceridemia Could Be an Etiological Factor in Chronic Pancreatitis Gurhan Sisman, Hakan Senturk, Ibrahim Hatemi, Rana Senturk, Sebati Ozdemir Introduction: Hypertriglyceridemia(HTG)can induce recurrent acute pancreatitis but its role in the etiology of chronic pancreatitis(CP)is controversial. Material and methods: We retrospectively analysed the clinical, laboratory and radiolgical findings of 4 CP patients with significant HTG without any other etiology and compared their data to the findings of CP without HTG. These four patients have had multiple attacks of pancreatitis and radiological features of chronic pancreatitis at abdominal tomography scan and/or at endosonography(EUS). According to Rosemont classification EUS features were consistent in 3 and suggestive in 1 patient. In all other patients diagnosis was based on Rosemont classification as well. Results: The comparison of the HTG group with the other CP group is showed in the table. The mean triglyceride level was 1768±1442 mg/dl in the first group. All four were smokers and non-drinkers. Portal vein thrombosis was present in two and pseudocyst in other two. All were diabetic with poor glycemic control requing insulin therapy. The frequency and
AGA Abstracts
S-854