Mo1415 Diabetes in Pancreatic Cancer Is Associated With Preferential Loss of Subcutaneous Over...
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AGA Abstracts Mo1413 Smoking and Family History of Cancer, Not Diabetes Mellitus, Were Associated With Younger Age of Onset in Japanese Pancreatic Cancer Patients Suguru Mizuno, Yousuke Nakai, Hiroyuki Isayama, Shuhei Kawahata, Kaoru Takagi, Tomotaka Saito, Takeo Watanabe, Rie Uchino, Tsuyoshi Hamada, Koji Miyabayashi, Hirofumi Kogure, Takashi Sasaki, Natsuyo Yamamoto, Kenji Hirano, Minoru Tada, Kazuhiko Koike Background: Smoking, alcohol or family history of specific cancers is reported to be associated with younger age of onset of pancreatic cancer (PC) in Western countries. We conducted this retrospective analysis to confirm these associations in Japanese PC patients. In addition, the association of diabetes mellitus (DM), which is bidirectionally related to PC, was evaluated. Methods: We retrospectively reviewed the medical records of 654 cases with PC diagnosed at our institute between Dec. 1993 and Oct. 2012. We examined the association between the onset age of PC and variables including gender, cigarette smoking, alcohol consumption, DM, and family history of cancer, especially PC. DM was defined as follows: fasting blood glucose was 126 mg/dl or more, HbA1c (National Glyocohemoglobin Standardization Pro- gram, NGSP) was 6.1% or more, or under medication for DM. Results: The mean age of PC diagnosis was 67.5 years (95% confidence interval [CI], 66.7-68.3) and 393 cases (60%) were male. DM was long-standing ( .2 years in duration) in 141 cases (21.6%) and new- onset (within 2 years in duration) in 174 cases (26.6%). In total, 315 cases (48.2%) had DM. Category of smoking habit was as follows: current smokers in 171, past smokers in 179, and never smokers in 304. Daily alcohol consumption was .80 g in 38 cases. Family history of cancer among first degree relatives was present in 221 patients: PC, 26 cases; colorectal cancer, 26 cases; breast cancer, 9 cases; and ovarian cancer, 2 cases. Current smokers were younger (63.7 [62.2-65.2] years, P ,0.001) at PC onset than past smokers (69.2 [67.7-70.7] years) and never smokers (68.5 [67.4-69.7] years); however, difference was not significant between current smokers and past smokers of cigarette abstinence within 10 years (n = 58, 65.2 [62.6-67.7] years, P = 0.346). Among current smokers, there was a dose-related decrease in onset age of PC. Heavy drinkers ( .80 g of alcohol/day) were associated with younger onset (63.7 [60.4-67.0] vs. 67.7 [66.9-68.5] years, P = 0.020). Male gender (-1.4 years, P = 0.085), family history of cancer (-3.1 years, P ,0.001), and family history of PC (-3.9 years, P = 0.061) were also associated with younger onset. Meanwhile, patients with long-standing DM were older (70.3 [68.6-72.0] years, P = 0.001) than those with new-onset DM (66.6 [65.1-68.2] years) and those without DM (66.7 [65.6- 67.8] years). In multivariate analysis, current smoker (-5.1 years, P ,0.001), long-standing DM (+3.6 years, P ,0.001), and family history of cancer (-3.1 years, P ,0.001) were significantly associated with onset age of PC. Conclusion: In Japanese PC patients, current smokers and family history of cancer were associated with younger age of onset of PC. Conversely, long-standing DM was associated with late onset of PC. Mo1414 The Risk Factors of Pancreatic Ductal Adenocarcinoma: A Hospital-Based Case-Control Study in Tottori, Japan Yohei Takeda, Kazuo Yashima, Takumi Onoyama, Kazuya Matsumoto, Koichiro Kawaguchi, Kenichi Harada, Yoshikazu Murawaki BACKGROUND: The diagnostic precision of pancreatic ductal adenocarcinoma (PDCA) improves with the drastic advances of the imaging diagnostic method. However, the prognosis and survival are very poor, because of deaths increases to the number of cases approximately in parallel. By surveillance for the high-risk individuals, early detection is essential for rescuing patients from this deadly disease. OBJECTIVES: The aim of this study was to establish the high-risk groups and proactive approaches for early detection of PDCA. METHODS: We retrospectively conducted a hospital-based case-control study involving 146 patients (95 males and 51 females) who was diagnosed PDCA pathologically, at Tottori University Hospital between July 2003 and August 2012. The control group comprised the same number of individuals matched for sex and age who tested positive for fecal occult blood as medical check-up during the same period. As for the risk factor of PDCA, complication of adult disease, chronic pancreatitis, intraductal papillary mucinus neoplasm, history of nonpan- creatic primary cancers, family history of malignant disease, tobacco and alcohol consump- tion, were examined. RESULTS: The mean age of PDCA patients and control groups were both 67.5±9.4yrs. Among PDCA patients, diabetics, smokers, and drinkers were more frequently in males than females (37% vs. 16%, 72% vs. 8%, 71% vs. 14%, P ,0.01). Females were more likely than males to have familial history of breast cancer (1% vs. 12%, P,0.01). Those who smoke more than one pack per day were younger than never-smoker (65.6 vs. 69.4 P=0.02). In female, alcohol users were younger than non-drinkers at their diagnosis (60.9 vs. 69.6 P=0.03). In comparison with the control group, PDCA patients had a significantly higher frequency of diabetes (37% vs. 16%, P=0.01). Male PDCA patients had significantly higher frequency of a previous history of a different cancer (32% vs. 20%, P=0.01). The breakdown of previous different cancer types among men revealed a high frequency of gastrointestinal cancer, including 10 cases of gastric cancer, 7 of colorectal cancer. In contrust, there was no significant difference between patients and controls in females. CONCLUSION: Tobacco dose was associated with the increased risk for earlier onset of PDCA. Men with a previous history of a different cancer, chiefly gastrointestinal cancer, may comprise a potential new risk group. Mo1415 Diabetes in Pancreatic Cancer Is Associated With Preferential Loss of Subcutaneous Over Visceral Fat Sajan Jiv Singh Nagpal, Naoki Takahashi, John M. Miles, Raghuwansh P. Sah, Gloria M. Petersen, Debabrata Mukhopadhyay, Suresh T. Chari Background/Aims: Weight gain leads to increase in visceral adipose tissue (VAT) which plays a key role in the development of type 2 DM and metabolic syndrome. Weight losing obese subjects have preferential loss of VAT over subcutaneous adipose tissue (SAT), leading to improved insulin sensitivity. Since pancreatic cancer (PaC) is associated with paradoxical S-660 AGA Abstracts development of glucose intolerance and diabetes (DM) in the face of ongoing, often profound, weight loss, we measured changes in SAT and VAT using abdominal CT scans in PaC before and after cancer diagnosis. Methods: We identified 111 PaC patients (mean age 71.02 years, 61.3% male) with 2 abdominal CT scans available for review; CT1 was done a median of 4 days from PaC diagnosis and CT2 was done a median 1123 days prior to diagnosis. By American Diabetes Association criteria PaC patients at diagnosis had normal fasting glucose (NFG, n=21), impaired fasting glucose (IFG, n=26), diabetes (DM, n= 59) or unknown DM status (n=5). Percentage body weight changes between the CT time points was classified as net weight gain (n=17) or % body weight lost of ,5% (n=15), 5-10% (n=15), .10% (n= 18) or unknown (n= 46). We measured SAT and VAT at L3/L4 vertebral level using a semi- automated protocol in the iNtuition software (TeraRecon Inc, USA). Results: Overall, PaC patients lost significantly more SAT than VAT (absolute change -37.96 vs -12.77 cm2, p ,.0001, % change -14.3 vs -4.81, p=0.04). This effect was significant only in those with elevated fasting glucose (IFG or DM), but not in those with normal fasting glucose (NFG) (Table). PaC patients (n=65) lost significant amount of weight between CT2 and CT1 (86.7 vs 81.3 kg, p,0.0001). The disproportionate loss of SAT over VAT was most pronounced in subjects with ,5% loss of body weight; the effect was attenuated in those with .5% body weight loss (Table). Conclusion: The relatively greater loss of SAT in patients with PaC could explain the paradox of weight loss in PaC not ameliorating DM (due to preservation of VAT). The differential effect of PaC on adipose tissue compartments also points to the presence of a specific PaC-associated associated lipid mobilizing factor with greater action on SAT than VAT. Comparison of changes in SAT and VAT at CT1 vs CT2 (t-test) * at diagnosis of PaC Mo1416 Fatty Pancreas Is a Risk Factor for PanIN Lesions Vinciane Rebours, Sebastien Gaujoux, Gaspard d'Assignies, Philippe B. Ruszniewski, Alain Sauvanet, Valérie Paradis, Pierre Bedossa, Philippe Levy, Anne Couvelard Obesity was recently described as a risk factor of pancreatic cancer with a specific link with significant metabolic abnormalities including insulin resistance, glucose intolerance and diabetes Aims: To characterize the frequency of pancreatic intraepithelial neoplasia (PanIN) in case of fatty pancreas, to correlate pathological findings with dysmetabolic characteristics and tobacco intake. Methods Consecutive pancreatic specimens of patients operated on for neuroendocrine tumors (NETs) (ductal tumors, ie adenocarcinomas and IPMN were excluded)) from 2009 to 2011 were analyzed. The pancreatic parenchyma was analyzed at least 2 cm apart from the tumor. Fatty infiltration and fibrosis of the parenchyma in intra and extra lobular locations were assessed by two investigators according to specific scores. Dysplastic lesions were described according to the WHO 2010 PanIN classification. General characteristics of the patients were collected, especially the body mass index (BMI), diabetes and tobacco intake. Results: 110 pancreatic specimens of patients (males: 42%) were analyzed (median surface per specimen: 7.5 cm2). Median age at surgery was 53.8 [17-85] years. Arterial hypertension, diabetes, tobacco consumption were found in 19%, 10% and 26%, respectively. Median BMI was 24 [16-37]. PanIN lesions type 1, 2 and 3 were observed in 62, 38 and 1% of cases, respectively. Fatty pancreas was found in 56% of cases (extralobular 30%, intralobular 51%). Intralobular fibrosis was noticed in 24% of cases. PanIN lesions were correlated to fatty pancreas (either extra- (0.005) or intra lobular (0.0001)), intralobular fibrosis (0.002), tobacco intake (0.05) and age at surgery (0.05). Fatty pancreas was associated with age (0.0001), higher BMI (0.05), intralobular fibrosis (0.009), hypertension ( ,0.001), hyperlipidemia (0.01) and diabetes (0.09). We found no correlation between PanIN lesions and dysmetabolic disorders. Conclusion: Fatty pancreas is an independent risk factor of PanIN lesions, especially in case of intralobular location. These results suggest that fatty infiltration itself plays a specific role in pancreatic oncogenesis. Mo1417 Association of HBsAg Positivity and Pancreatic Cancer: A Meta-Analysis Shounak Majumder, Bruno Bockorny, William L. Baker OBJECTIVE: Several studies have proposed an association between Hepatitis B infection and pancreatic cancer. Although the spectrum of serological tests varied between studies, Hepatitis B surface antigen (HBsAg) test results were reported by all. We carried out a meta-analysis to evaluate the association between HBsAg positivity and pancreatic cancer. METHODS: A systematic MEDLINE and SCOPUS review was performed from inception through September 2012 for English language studies using the following terms: "hepatitis B", "chronic hepatitis B", "HBsAg", "pancreatic cancer", and "pancreatic adenocarcinoma". Cross-reference was checked for the studies that met selection criteria. Case-control and cohort studies were included. Studies that have not reported a cumulative odds ratio for the association of
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Smoking and Family History of Cancer, Not Diabetes Mellitus, WereAssociated With Younger Age of Onset in Japanese Pancreatic Cancer PatientsSuguru Mizuno, Yousuke Nakai, Hiroyuki Isayama, Shuhei Kawahata, Kaoru Takagi,Tomotaka Saito, Takeo Watanabe, Rie Uchino, Tsuyoshi Hamada, Koji Miyabayashi,Hirofumi Kogure, Takashi Sasaki, Natsuyo Yamamoto, Kenji Hirano, Minoru Tada,Kazuhiko Koike
Background: Smoking, alcohol or family history of specific cancers is reported to be associatedwith younger age of onset of pancreatic cancer (PC) in Western countries. We conductedthis retrospective analysis to confirm these associations in Japanese PC patients. In addition,the association of diabetes mellitus (DM), which is bidirectionally related to PC, was evaluated.Methods: We retrospectively reviewed the medical records of 654 cases with PC diagnosedat our institute between Dec. 1993 and Oct. 2012. We examined the association betweenthe onset age of PC and variables including gender, cigarette smoking, alcohol consumption,DM, and family history of cancer, especially PC. DM was defined as follows: fasting bloodglucose was 126 mg/dl or more, HbA1c (National Glyocohemoglobin Standardization Pro-gram, NGSP) was 6.1% or more, or under medication for DM. Results: The mean age ofPC diagnosis was 67.5 years (95% confidence interval [CI], 66.7-68.3) and 393 cases (60%)were male. DM was long-standing (.2 years in duration) in 141 cases (21.6%) and new-onset (within 2 years in duration) in 174 cases (26.6%). In total, 315 cases (48.2%) hadDM. Category of smoking habit was as follows: current smokers in 171, past smokers in179, and never smokers in 304. Daily alcohol consumption was .80 g in 38 cases. Familyhistory of cancer among first degree relatives was present in 221 patients: PC, 26 cases;colorectal cancer, 26 cases; breast cancer, 9 cases; and ovarian cancer, 2 cases. Currentsmokers were younger (63.7 [62.2-65.2] years, P ,0.001) at PC onset than past smokers(69.2 [67.7-70.7] years) and never smokers (68.5 [67.4-69.7] years); however, differencewas not significant between current smokers and past smokers of cigarette abstinence within10 years (n = 58, 65.2 [62.6-67.7] years, P = 0.346). Among current smokers, there was adose-related decrease in onset age of PC. Heavy drinkers ( .80 g of alcohol/day) wereassociated with younger onset (63.7 [60.4-67.0] vs. 67.7 [66.9-68.5] years, P = 0.020).Male gender (-1.4 years, P = 0.085), family history of cancer (-3.1 years, P ,0.001), andfamily history of PC (-3.9 years, P = 0.061) were also associated with younger onset.Meanwhile, patients with long-standing DM were older (70.3 [68.6-72.0] years, P = 0.001)than those with new-onset DM (66.6 [65.1-68.2] years) and those without DM (66.7 [65.6-67.8] years). In multivariate analysis, current smoker (-5.1 years, P ,0.001), long-standingDM (+3.6 years, P ,0.001), and family history of cancer (-3.1 years, P ,0.001) weresignificantly associated with onset age of PC. Conclusion: In Japanese PC patients, currentsmokers and family history of cancer were associated with younger age of onset of PC.Conversely, long-standing DM was associated with late onset of PC.
Mo1414
The Risk Factors of Pancreatic Ductal Adenocarcinoma: A Hospital-BasedCase-Control Study in Tottori, JapanYohei Takeda, Kazuo Yashima, Takumi Onoyama, Kazuya Matsumoto, KoichiroKawaguchi, Kenichi Harada, Yoshikazu Murawaki
BACKGROUND: The diagnostic precision of pancreatic ductal adenocarcinoma (PDCA)improves with the drastic advances of the imaging diagnostic method. However, the prognosisand survival are very poor, because of deaths increases to the number of cases approximatelyin parallel. By surveillance for the high-risk individuals, early detection is essential forrescuing patients from this deadly disease. OBJECTIVES: The aim of this study was to establishthe high-risk groups and proactive approaches for early detection of PDCA. METHODS: Weretrospectively conducted a hospital-based case-control study involving 146 patients (95males and 51 females) who was diagnosed PDCA pathologically, at Tottori University Hospitalbetween July 2003 and August 2012. The control group comprised the same number ofindividuals matched for sex and age who tested positive for fecal occult blood as medicalcheck-up during the same period. As for the risk factor of PDCA, complication of adultdisease, chronic pancreatitis, intraductal papillary mucinus neoplasm, history of nonpan-creatic primary cancers, family history of malignant disease, tobacco and alcohol consump-tion, were examined. RESULTS: The mean age of PDCA patients and control groups wereboth 67.5±9.4yrs. Among PDCA patients, diabetics, smokers, and drinkers were morefrequently in males than females (37% vs. 16%, 72% vs. 8%, 71% vs. 14%, P ,0.01).Females were more likely than males to have familial history of breast cancer (1% vs. 12%,P,0.01). Those who smoke more than one pack per day were younger than never-smoker(65.6 vs. 69.4 P=0.02). In female, alcohol users were younger than non-drinkers at theirdiagnosis (60.9 vs. 69.6 P=0.03). In comparison with the control group, PDCA patients hada significantly higher frequency of diabetes (37% vs. 16%, P=0.01). Male PDCA patientshad significantly higher frequency of a previous history of a different cancer (32% vs. 20%,P=0.01). The breakdown of previous different cancer types among men revealed a highfrequency of gastrointestinal cancer, including 10 cases of gastric cancer, 7 of colorectalcancer. In contrust, there was no significant difference between patients and controls infemales. CONCLUSION: Tobacco dose was associated with the increased risk for earlieronset of PDCA. Men with a previous history of a different cancer, chiefly gastrointestinalcancer, may comprise a potential new risk group.
Mo1415
Diabetes in Pancreatic Cancer Is Associated With Preferential Loss ofSubcutaneous Over Visceral FatSajan Jiv Singh Nagpal, Naoki Takahashi, John M. Miles, Raghuwansh P. Sah, Gloria M.Petersen, Debabrata Mukhopadhyay, Suresh T. Chari
Background/Aims: Weight gain leads to increase in visceral adipose tissue (VAT) whichplays a key role in the development of type 2 DM and metabolic syndrome. Weight losingobese subjects have preferential loss of VAT over subcutaneous adipose tissue (SAT), leadingto improved insulin sensitivity. Since pancreatic cancer (PaC) is associated with paradoxical
S-660AGA Abstracts
development of glucose intolerance and diabetes (DM) in the face of ongoing, often profound,weight loss, we measured changes in SAT and VAT using abdominal CT scans in PaC beforeand after cancer diagnosis. Methods: We identified 111 PaC patients (mean age 71.02 years,61.3% male) with 2 abdominal CT scans available for review; CT1 was done a median of4 days from PaC diagnosis and CT2 was done a median 1123 days prior to diagnosis. ByAmerican Diabetes Association criteria PaC patients at diagnosis had normal fasting glucose(NFG, n=21), impaired fasting glucose (IFG, n=26), diabetes (DM, n= 59) or unknown DMstatus (n=5). Percentage body weight changes between the CT time points was classified asnet weight gain (n=17) or % body weight lost of ,5% (n=15), 5-10% (n=15), .10% (n=18) or unknown (n= 46). We measured SAT and VAT at L3/L4 vertebral level using a semi-automated protocol in the iNtuition software (TeraRecon Inc, USA). Results: Overall, PaCpatients lost significantly more SAT than VAT (absolute change -37.96 vs -12.77 cm2, p,.0001, % change -14.3 vs -4.81, p=0.04). This effect was significant only in those withelevated fasting glucose (IFG or DM), but not in those with normal fasting glucose (NFG)(Table). PaC patients (n=65) lost significant amount of weight between CT2 and CT1 (86.7vs 81.3 kg, p,0.0001). The disproportionate loss of SAT over VAT was most pronouncedin subjects with ,5% loss of body weight; the effect was attenuated in those with .5%body weight loss (Table). Conclusion: The relatively greater loss of SAT in patients withPaC could explain the paradox of weight loss in PaC not ameliorating DM (due to preservationof VAT). The differential effect of PaC on adipose tissue compartments also points to thepresence of a specific PaC-associated associated lipid mobilizing factor with greater actionon SAT than VAT.Comparison of changes in SAT and VAT at CT1 vs CT2 (t-test)
* at diagnosis of PaC
Mo1416
Fatty Pancreas Is a Risk Factor for PanIN LesionsVinciane Rebours, Sebastien Gaujoux, Gaspard d'Assignies, Philippe B. Ruszniewski, AlainSauvanet, Valérie Paradis, Pierre Bedossa, Philippe Levy, Anne Couvelard
Obesity was recently described as a risk factor of pancreatic cancer with a specific link withsignificant metabolic abnormalities including insulin resistance, glucose intolerance anddiabetes Aims: To characterize the frequency of pancreatic intraepithelial neoplasia (PanIN)in case of fatty pancreas, to correlate pathological findings with dysmetabolic characteristicsand tobacco intake. Methods Consecutive pancreatic specimens of patients operated on forneuroendocrine tumors (NETs) (ductal tumors, ie adenocarcinomas and IPMN wereexcluded)) from 2009 to 2011 were analyzed. The pancreatic parenchyma was analyzed atleast 2 cm apart from the tumor. Fatty infiltration and fibrosis of the parenchyma in intraand extra lobular locations were assessed by two investigators according to specific scores.Dysplastic lesions were described according to the WHO 2010 PanIN classification. Generalcharacteristics of the patients were collected, especially the body mass index (BMI), diabetesand tobacco intake. Results: 110 pancreatic specimens of patients (males: 42%) were analyzed(median surface per specimen: 7.5 cm2). Median age at surgery was 53.8 [17-85] years.Arterial hypertension, diabetes, tobacco consumption were found in 19%, 10% and 26%,respectively. Median BMI was 24 [16-37]. PanIN lesions type 1, 2 and 3 were observed in62, 38 and 1% of cases, respectively. Fatty pancreas was found in 56% of cases (extralobular30%, intralobular 51%). Intralobular fibrosis was noticed in 24% of cases. PanIN lesionswere correlated to fatty pancreas (either extra- (0.005) or intra lobular (0.0001)), intralobularfibrosis (0.002), tobacco intake (0.05) and age at surgery (0.05). Fatty pancreas was associatedwith age (0.0001), higher BMI (0.05), intralobular fibrosis (0.009), hypertension ( ,0.001),hyperlipidemia (0.01) and diabetes (0.09). We found no correlation between PanIN lesionsand dysmetabolic disorders. Conclusion: Fatty pancreas is an independent risk factor ofPanIN lesions, especially in case of intralobular location. These results suggest that fattyinfiltration itself plays a specific role in pancreatic oncogenesis.
Mo1417
Association of HBsAg Positivity and Pancreatic Cancer: A Meta-AnalysisShounak Majumder, Bruno Bockorny, William L. Baker
OBJECTIVE: Several studies have proposed an association between Hepatitis B infection andpancreatic cancer. Although the spectrum of serological tests varied between studies, HepatitisB surface antigen (HBsAg) test results were reported by all. We carried out a meta-analysisto evaluate the association between HBsAg positivity and pancreatic cancer. METHODS: Asystematic MEDLINE and SCOPUS review was performed from inception through September2012 for English language studies using the following terms: "hepatitis B", "chronic hepatitisB", "HBsAg", "pancreatic cancer", and "pancreatic adenocarcinoma". Cross-reference waschecked for the studies that met selection criteria. Case-control and cohort studies wereincluded. Studies that have not reported a cumulative odds ratio for the association of
