The Epidemiology of Pancreatitis and Pancreatic Cancer

Acute pancreatitis is one of the most frequent gastrointestinal causes of hospital admission in the United States. Chronic pancreatitis, although lower in incidence, significantly reduces patients' quality of life. Pancreatic cancer is associated with a high mortality rate and is one of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect the black population more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter the progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer. Acute pancreatitis is one of the most frequent gastrointestinal causes of hospital admission in the United States. Chronic pancreatitis, although lower in incidence, significantly reduces patients' quality of life. Pancreatic cancer is associated with a high mortality rate and is one of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect the black population more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter the progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer. View Large Image Figure ViewerDownload Hi-res image Download (PPT)Descriptive EpidemiologyIncidence, Prevalence, and TrendsThe annual incidence of AP3Satoh K. Shimosegawa T. Masamune A. et al.Nationwide epidemiological survey of acute pancreatitis in Japan.Pancreas. 2011; 40: 503-507Crossref PubMed Scopus (16) Google Scholar, 4Shen H.N. Lu C.L. Li C.Y. Epidemiology of first-attack acute pancreatitis in Taiwan from 2000 through 2009: a nationwide population-based study.Pancreas. 2012; 41: 696-702Crossref PubMed Scopus (74) Google Scholar, 5Yadav D. Whitcomb D.C. The role of alcohol and smoking in pancreatitis.Nat Rev Gastroenterol Hepatol. 2010; 7: 131-145Crossref PubMed Scopus (43) Google Scholar ranges from 13 to 45/100,000 persons and of CP5Yadav D. Whitcomb D.C. The role of alcohol and smoking in pancreatitis.Nat Rev Gastroenterol Hepatol. 2010; 7: 131-145Crossref PubMed Scopus (43) Google Scholar, 6Hirota M. Shimosegawa T. Masamune A. et al.The sixth nationwide epidemiological survey of chronic pancreatitis in Japan.Pancreatology. 2012; 12: 79-84Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar ranges from 5 to 12/100,000; the prevalence of CP is about 50/100,000 persons.6Hirota M. Shimosegawa T. Masamune A. et al.The sixth nationwide epidemiological survey of chronic pancreatitis in Japan.Pancreatology. 2012; 12: 79-84Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 7Yadav D. Timmons L. Benson J.T. et al.Incidence, prevalence, and survival of chronic pancreatitis: a population-based study.Am J Gastroenterol. 2011; 106: 2192-2199Crossref PubMed Scopus (9) Google Scholar The incidence of pancreatitis and pancreatic cancer in the United States is shown in Figure 1.8Frey C.F. Zhou H. Harvey D.J. et al.The incidence and case-fatality rates of acute biliary, alcoholic, and idiopathic pancreatitis in California, 1994-2001.Pancreas. 2006; 33: 336-344Crossref PubMed Scopus (96) Google Scholar, 9National Cancer Institutehttp://seer cancer gov/statfacts/html/pancreas htmlGoogle Scholar Population distributions are mostly reported from the United States, Europe, and Japan, but data are emerging from other regions.4Shen H.N. Lu C.L. Li C.Y. Epidemiology of first-attack acute pancreatitis in Taiwan from 2000 through 2009: a nationwide population-based study.Pancreas. 2012; 41: 696-702Crossref PubMed Scopus (74) Google Scholar Variations in disease estimates result from differences in study methodology, difficulties in establishing accurate diagnoses, the use of different diagnostic criteria, and local lifestyle risk factors.10Yadav D. Lowenfels A.B. Trends in the epidemiology of the first attack of acute pancreatitis: a systematic review.Pancreas. 2006; 33: 323-330Crossref PubMed Scopus (146) Google Scholar Further, analyses that use administrative data or include nonunique patients can increase estimates. There are also regional differences in demographic distributions; alcohol-related pancreatitis is more common in the West and Japan compared with other Asian countries, and there is wide variation in the prevalence of a form of CP that is endemic to tropical countries (20–125/100,000 persons reported in 2 parts of South India).11Mohan V. Farooq S. Deepa M. Prevalence of fibrocalculous pancreatic diabetes in Chennai in South India.JOP. 2008; 9: 489-492PubMed Google Scholar, 12Balaji L.N. Tandon R.K. Tandon B.N. et al.Prevalence and clinical features of chronic pancreatitis in southern India.Int J Pancreatol. 1994; 15: 29-34PubMed Google ScholarFigure 1Incidence rates for pancreatitis and pancreatic cancer in the United States. Numbers in parentheses indicate approximate yearly incidence rates per 100,000 persons. The arrow indicates the relationship between benign and malignant disease. Recurrent AP develops predominantly in patients with non–gallstone-related pancreatitis, although it can develop in patients with gallstone-related pancreatitis when cholecystectomy has been delayed or refused.8Frey C.F. Zhou H. Harvey D.J. et al.The incidence and case-fatality rates of acute biliary, alcoholic, and idiopathic pancreatitis in California, 1994-2001.Pancreas. 2006; 33: 336-344Crossref PubMed Scopus (96) Google Scholar, 9National Cancer Institutehttp://seer cancer gov/statfacts/html/pancreas htmlGoogle Scholar, 24Yadav D. Muddana V. O'Connell M. Hospitalizations for chronic pancreatitis in Allegheny County, Pennsylvania, USA.Pancreatology. 2011; 11: 546-552Abstract Full Text PDF PubMed Scopus (1) Google ScholarView Large Image Figure ViewerDownload Hi-res image Download (PPT)A large increase in the incidence of AP and a smaller increase in the incidence of CP have been reported in population studies.6Hirota M. Shimosegawa T. Masamune A. et al.The sixth nationwide epidemiological survey of chronic pancreatitis in Japan.Pancreatology. 2012; 12: 79-84Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 7Yadav D. Timmons L. Benson J.T. et al.Incidence, prevalence, and survival of chronic pancreatitis: a population-based study.Am J Gastroenterol. 2011; 106: 2192-2199Crossref PubMed Scopus (9) Google Scholar, 10Yadav D. Lowenfels A.B. Trends in the epidemiology of the first attack of acute pancreatitis: a systematic review.Pancreas. 2006; 33: 323-330Crossref PubMed Scopus (146) Google Scholar The increasing incidence of obesity is likely to contribute to that of AP because obesity promotes gallstone formation, which is the most common cause of AP. Another major contributor is increased availability and use of tests to measure serum levels of pancreatic enzymes, which detect milder cases of AP but can also result in overdiagnosis.13Saligram S. Lo D. Saul M. et al.Analyses of hospital administrative data that use diagnosis codes overestimate the cases of acute pancreatitis.Clin Gastroenterol Hepatol. 2012; 10: 805-811 e1Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar In the United States, emergency department use of tests to measure serum pancreatic enzyme levels reportedly increased by more than 60% over a 10-year period.14Yadav D. Ng B. Saul M. et al.Relationship of serum pancreatic enzyme testing trends with the diagnosis of acute pancreatitis.Pancreas. 2011; 40: 383-389Crossref PubMed Scopus (4) Google ScholarIncreases in the prevalence of CP could result from greater availability of high-quality cross-sectional imaging techniques that can detect morphologic changes in the pancreas. Alcohol consumption has been increasing in developing countries, such as China and India,15Global Status Report on Alcohol and Health 2011.http://www.who.int/substance_abuse/publications/global_alcohol_report/en/index.htmlGoogle Scholar due to rapid urbanization and increased affluence. This increase would be expected to increase the burden of alcohol-related pancreatitis in these countries. In contrast, alcohol consumption has been generally stable or decreased in many North American and European countries.The global annual incidence rate of pancreatic cancer is approximately 8/100,000 persons.16Raimondi S. Maisonneuve P. Lowenfels A.B. Epidemiology of pancreatic cancer: an overview.Nat Rev Gastroenterol Hepatol. 2009; 6: 699-708Crossref PubMed Scopus (116) Google Scholar Adenocarcinoma is the most frequent type of pancreatic cancer; slower-growing endocrine tumors account for only a small fraction of the total burden of disease. As for nearly all cancers, incidence rates of pancreatic cancer vary among countries, with approximate 5- to 7-fold differences between countries with the lowest and highest incidence; rates reported from African countries are low because of insufficient data. There has been a concerted search for environmental factors that might account for this variation. In addition to country-specific differences, there are subtle geographic and regional differences; countries located on or close to the equator have lower rates than antipodal countries. In 2008, there were an estimated 279,000 new diagnoses of pancreatic cancer worldwide, accounting for 2.2% of all new cases of cancer.17World wide cancer statistics.www.wcrf.org/cancer_statistics/world_cancerstatistics phpGoogle ScholarAge and SexAlthough equal proportions of men and women develop AP, CP is more common among men. The risk of AP progressively increases with age, whereas CP mainly affects middle-aged individuals. Age and sex distribution differ based on etiology (see Figure 2, Figure 3). Alcohol-related pancreatitis is more common in men, although sex differences disappear with similar levels of alcohol consumption.18Lankisch P.G. Lowenfels A.B. Maisonneuve P. What is the risk of alcoholic pancreatitis in heavy drinkers?.Pancreas. 2002; 25: 411-412Crossref PubMed Scopus (50) Google Scholar Studies are needed to determine whether genetic factors increase risk in men. Pancreatitis in women is more likely related to gallstones, endoscopic retrograde cholangiopancreatography, or autoimmune diseases or to be idiopathic. Variations in age and sex distribution among geographic regions likely arise from differences in etiology.19Garg P.K. Chronic pancreatitis in India and Asia.Curr Gastroenterol Rep. 2012; 14: 118-124Crossref PubMed Scopus (1) Google Scholar Although pancreatitis is uncommon among persons younger than 20 years of age, it is increasingly recognized in the pediatric population.20Morinville V.D. Barmada M.M. Lowe M.E. Increasing incidence of acute pancreatitis at an American pediatric tertiary care center: is greater awareness among physicians responsible?.Pancreas. 2009; 39: 5-8Crossref Scopus (18) Google Scholar Common etiologies of AP in pediatric patients include gallstones, medication, and idiopathic disease.21Bai H.X. Lowe M.E. Husain S.Z. What have we learned about acute pancreatitis in children?.J Pediatr Gastroenterol Nutr. 2011; 52: 262-270Crossref PubMed Scopus (19) Google Scholar Genetic factors are likely to contribute to unexplained recurrent AP or CP.22Lucidi V. Alghisi F. Dall'Oglio L. et al.The etiology of acute recurrent pancreatitis in children: a challenge for pediatricians.Pancreas. 2011; 40: 517-521Crossref PubMed Scopus (7) Google Scholar, 23Sultan M. Werlin S. Venkatasubramani N. Genetic prevalence and characteristics in children with recurrent pancreatitis.J Pediatr Gastroenterol Nutr. 2012; 54: 645-650Crossref PubMed Scopus (6) Google ScholarFigure 2Incidence of AP from 1996 to 2005 in white and black residents of Allegheny County, Pennsylvania, based on age group, sex, and etiology. Data on incidence are shown only for patients with alcohol, gallstone, or idiopathic etiology. Rate for all patients is age, sex, and race adjusted to the 2000 US white and black population.Source: Allegheny County census data (http://www.cdc.gov/nchs/nvss.htm) and data derived from Yadav et al113Yadav D. O'Connell M. Papachristou G.I. Natural history following the first attack of acute pancreatitis.Am J Gastroenterol. 2012; 107: 1096-1103Crossref PubMed Scopus (9) Google Scholar are reprinted with permission.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3Prevalence of CP in 2006 in Olmsted County, Minnesota, based on age group, sex, and etiology. Rate for all patients is age and sex adjusted to 2000 US white population.Data are derived from Yadav et al7Yadav D. Timmons L. Benson J.T. et al.Incidence, prevalence, and survival of chronic pancreatitis: a population-based study.Am J Gastroenterol. 2011; 106: 2192-2199Crossref PubMed Scopus (9) Google Scholar and are reprinted with permission.View Large Image Figure ViewerDownload Hi-res image Download (PPT)As for other cancers, less than 10% of cases of pancreatic cancer occur among individuals younger than 55 years of age, and the median age of onset is 71 years. Figure 4 compares US rates of pancreatic cancer by sex, race, and ethnicity. In all groups, men have higher incidence rates than women.Figure 4Incidence of pancreatic cancer from 2005 to 2009 in the United States, based on sex and racial groups.9National Cancer Institutehttp://seer cancer gov/statfacts/html/pancreas htmlGoogle ScholarView Large Image Figure ViewerDownload Hi-res image Download (PPT)RaceThe risk of pancreatitis is 2- to 3-fold higher among the black population than the white population,2Yang A.L. Vadhavkar S. Singh G. et al.Epidemiology of alcohol-related liver and pancreatic disease in the United States.Arch Intern Med. 2008; 168: 649-656Crossref PubMed Scopus (40) Google Scholar, 24Yadav D. Muddana V. O'Connell M. Hospitalizations for chronic pancreatitis in Allegheny County, Pennsylvania, USA.Pancreatology. 2011; 11: 546-552Abstract Full Text PDF PubMed Scopus (1) Google Scholar and rates of pancreatic cancer are considerably higher in the black population than in any other racial group,9National Cancer Institutehttp://seer cancer gov/statfacts/html/pancreas htmlGoogle Scholar which is a disparity similar to that of lung cancer. Little is known about the reasons for the racial disparity, and further research is urgently needed. Distributions of lifestyle factors, such as heavy drinking or smoking, are similar among the US black and white populations.25National Center for Health StatisticsHealth US, 2011: with special feature on socioeconomic status and health.2012Google Scholar Studies are needed to determine whether the observed differences result from dietary, genetic, or other factors.Lifestyle FactorsAlcoholAlthough patients who have never consumed alcohol can develop pancreatitis, alcohol appears to increase the sensitivity of the pancreas to injury from other factors (genetic or environmental),26Pandol SJ, Lugea A, Mareninova OA, et al. Investigating the pathobiology of alcoholic pancreatitis. Alcohol Clin Exp Res;35:830–837.Google Scholar and the risk of pancreatitis is undoubtedly increased by alcohol consumption. The prevalence of pancreatitis is increased approximately 4-fold among subjects with a history of alcoholism compared with those without.27Yadav D. Eigenbrodt M.L. Briggs M.J. et al.Pancreatitis: prevalence and risk factors among male veterans in a detoxification program.Pancreas. 2007; 34: 390-398Crossref PubMed Scopus (19) Google Scholar The absolute risk of pancreatitis from alcohol consumption is much lower than that for chronic liver disease or cirrhosis and ranges from 2% to 5% among patients who consume large amounts of alcohol.18Lankisch P.G. Lowenfels A.B. Maisonneuve P. What is the risk of alcoholic pancreatitis in heavy drinkers?.Pancreas. 2002; 25: 411-412Crossref PubMed Scopus (50) Google Scholar, 27Yadav D. Eigenbrodt M.L. Briggs M.J. et al.Pancreatitis: prevalence and risk factors among male veterans in a detoxification program.Pancreas. 2007; 34: 390-398Crossref PubMed Scopus (19) Google Scholar, 28Kristiansen L. Gronbaek M. Becker U. et al.Risk of pancreatitis according to alcohol drinking habits: a population-based cohort study.Am J Epidemiol. 2008; 168: 932-937Crossref PubMed Scopus (32) Google Scholar Alcohol use is the single most common cause of CP29Cote G.A. Yadav D. Slivka A. et al.Alcohol and smoking as risk factors in an epidemiology study of patients with chronic pancreatitis.Clin Gastroenterol Hepatol. 2011; 9 (quiz e27): 266-273Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar, 30Frulloni L. Gabbrielli A. Pezzilli R. et al.Chronic pancreatitis: report from a multicenter Italian survey (PanCroInfAISP) on 893 patients.Dig Liver Dis. 2009; 41: 311-317Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar (its attributable risk is approximately 40%) and after gallstones is the second most common cause of AP.10Yadav D. Lowenfels A.B. Trends in the epidemiology of the first attack of acute pancreatitis: a systematic review.Pancreas. 2006; 33: 323-330Crossref PubMed Scopus (146) Google ScholarAlcohol was shown to increase the risk of pancreatitis in a dose-dependent manner in a recent cohort study.28Kristiansen L. Gronbaek M. Becker U. et al.Risk of pancreatitis according to alcohol drinking habits: a population-based cohort study.Am J Epidemiol. 2008; 168: 932-937Crossref PubMed Scopus (32) Google Scholar The risk of CP increases at a threshold of approximately 5 drinks/day (odds ratio, 3.1)31Yadav D. Hawes R.H. Brand R.E. et al.Alcohol consumption, cigarette smoking, and the risk of recurrent acute and chronic pancreatitis.Arch Intern Med. 2009; 169: 1035-1045Crossref PubMed Scopus (78) Google Scholar based on a large case-control study or at 4 drinks/day based on a meta-analysis of the published literature (relative risk, 2.5).32Irving H.M. Samokhvalov A.V. Rehm J. Alcohol as a risk factor for pancreatitis A systematic review and meta-analysis.JOP. 2009; 10: 387-392PubMed Google Scholar These data indicate a clear increase in risk among heavy drinkers, although lower levels of alcohol consumption might not be completely safe, especially among subjects who have had an episode of alcohol-related AP or are diagnosed with CP.After patients had a first episode of alcohol-related AP, their risk of progression to CP was approximately 14% with complete abstinence or only occasional drinking, 23% with decreased but daily drinking, and 41% with drinking at the same levels as before the attack of AP.33Takeyama Y. Long-term prognosis of acute pancreatitis in Japan.Clin Gastroenterol Hepatol. 2009; 7: S15-S17Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar A randomized controlled trial reported that the risk of recurrence after a first episode of acute alcohol-related AP decreased significantly following repeated counseling against alcohol consumption.34Nordback I. Pelli H. Lappalainen-Lehto R. et al.The recurrence of acute alcohol-associated pancreatitis can be reduced: a randomized controlled trial.Gastroenterology. 2009; 136: 848-855Abstract Full Text Full Text PDF PubMed Scopus (36) Google ScholarTwo cohort studies have examined the relationship between pancreatitis and consumption of different types of alcohol.28Kristiansen L. Gronbaek M. Becker U. et al.Risk of pancreatitis according to alcohol drinking habits: a population-based cohort study.Am J Epidemiol. 2008; 168: 932-937Crossref PubMed Scopus (32) Google Scholar, 35Sadr Azodi O. Orsini N. Andren-Sandberg A. et al.Effect of type of alcoholic beverage in causing acute pancreatitis.Br J Surg. 2011; 98: 1609-1616Crossref PubMed Scopus (6) Google Scholar A Danish study associated pancreatitis with consumption of >14 beers/week but not wine or spirits.28Kristiansen L. Gronbaek M. Becker U. et al.Risk of pancreatitis according to alcohol drinking habits: a population-based cohort study.Am J Epidemiol. 2008; 168: 932-937Crossref PubMed Scopus (32) Google Scholar A Swedish study associated AP with 5 or more drinks of spirits on a single occasion but not with beer or wine.35Sadr Azodi O. Orsini N. Andren-Sandberg A. et al.Effect of type of alcoholic beverage in causing acute pancreatitis.Br J Surg. 2011; 98: 1609-1616Crossref PubMed Scopus (6) Google Scholar One limitation of these analyses was the small numbers of subjects in the heavy-drinking groups, who have the greatest risk of developing pancreatitis. Pancreatitis is observed in all populations, irrespective of the type of beverage they consume, but the contribution of beverage type to risk requires further study.With regard to binge drinking, a study compared the number and frequency of hospital admissions of patients with AP during the Munich Oktoberfest with 2 other time periods and found no significant increase during this 16-day period of increased beer drinking.36Phillip V. Huber W. Hagemes F. et al.Incidence of acute pancreatitis does not increase during Oktoberfest, but is higher than previously described in Germany.Clin Gastroenterol Hepatol. 2011; 9 (e3): 995-1000Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar In this study, a brief period of increased drinking (above baseline low levels) did not appear to increase the risk of AP at a population level. The risk seems to be higher in patients with a prior history of heavy drinking, many of whom report an increase in alcohol consumption during the weeks preceding their attack. An interesting study from The Netherlands found that approximately 50% of patients with alcohol-related AP developed symptoms 2 days after they stopped drinking,37Nordback I. Pelli H. Lappalainen-Lehto R. et al.Is it long-term continuous drinking or the post-drinking withdrawal period that triggers the first acute alcoholic pancreatitis?.Scand J Gastroenterol. 2005; 40: 1235-1239Crossref PubMed Scopus (9) Google Scholar raising questions about whether the amount, duration, and/or withdrawal of binge drinking affect the risk of AP.It is difficult to implicate alcohol as an independent risk factor for pancreatic cancer because of the close association between alcohol and smoking, which is a proven risk factor for pancreatic cancer. If alcohol affects the pathogenesis of pancreatitis, it could promote the effects of other risk factors such as smoking. Recent studies concluded that heavy drinkers might have an increased risk of pancreatic cancer. Gapstur et al, in a study of nonsmokers, observed an increased risk of pancreatic cancer only among persons who consumed more than 3 drinks per day.38Gapstur S.M. Jacobs E.J. Deka A. et al.Association of alcohol intake with pancreatic cancer mortality in never smokers.Arch Intern Med. 2011; 171: 444-451Crossref PubMed Scopus (13) Google Scholar Examining 10 case-control studies, Lucenteforte et al found an increased risk of pancreatic cancer among persons who consumed more than 9 drinks per day.39Lucenteforte E. La Vecchia C. Silverman D. et al.Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4).Ann Oncology. 2012; 23: 374-382Crossref PubMed Scopus (15) Google ScholarSmokingSince 1982, when smoking was initially reported as a risk factor for CP,40Yen S. Hsieh C.C. MacMahon B. Consumption of alcohol and tobacco and other risk factors for pancreatitis.Am J Epidemiol. 1982; 116: 407-414Crossref PubMed Google Scholar numerous studies have confirmed this association. Smoking and alcohol are cofactors that increase the risk of pancreatitis. In a multicenter study, ever and current smoking was reported by 71.4% and 47.3% of patients with CP, respectively, at the time of enrollment. Drinking and smoking habits often coexist, and the prevalence of smoking was found to increase with the amount of alcohol consumed.31Yadav D. Hawes R.H. Brand R.E. et al.Alcohol consumption, cigarette smoking, and the risk of recurrent acute and chronic pancreatitis.Arch Intern Med. 2009; 169: 1035-1045Crossref PubMed Scopus (78) Google ScholarA meta-analysis of 12 studies of approximately 1500 patients with CP associated levels of smoking with CP. The excess risk of CP was more than 2-fold (relative risk, 2.4) among subjects who smoked less than one pack/day and more than 3-fold (relative risk, 3.3) among those who smoked one or more packs/day. The risk was higher for current smokers (relative risk, 2.5) and significantly lower among former smokers (relative risk, 1.4).41Andriulli A. Botteri E. Almasio P.L. et al.Smoking as a cofactor for causation of chronic pancreatitis: a meta-analysis.Pancreas. 2010; 39: 1205-1210Crossref PubMed Scopus (29) Google Scholar Although smoking increases the risk of CP independently of alcohol, the effects of smoking are stronger for alcohol-related CP.Smoking also increases the risk of AP.42Lindkvist B. Appelros S. Manjer J. et al.A prospective cohort study of smoking in acute pancreatitis.Pancreatology. 2008; 8: 63-70Abstract Full Text PDF PubMed Scopus (39) Google Scholar, 43Sadr-Azodi O. Andren-Sandberg A. Orsini N. et al.Cigarette smoking, smoking cessation and acute pancreatitis: a prospective population-based study.Gut. 2012; 61: 262-267Crossref PubMed Scopus (14) Google Scholar, 44Tolstrup J.S. Kristiansen L. Becker U. et al.Smoking and risk of acute and chronic pancreatitis among women and men: a population-based cohort study.Arch Intern Med. 2009; 169: 603-609Crossref PubMed Scopus (33) Google Scholar A Swedish study43Sadr-Azodi O. Andren-Sandberg A. Orsini N. et al.Cigarette smoking, smoking cessation and acute pancreatitis: a prospective population-based study.Gut. 2012; 61: 262-267Crossref PubMed Scopus (14) Google Scholar found that smoking increased the risk of non-gallstone-related (by approximately 2-fold) but not gallstone-related AP.43Sadr-Azodi O. Andren-Sandberg A. Orsini N. et al.Cigarette smoking, smoking cessation and acute pancreatitis: a prospective population-based study.Gut. 2012; 61: 262-267Crossref PubMed Scopus (14) Google Scholar The risk was especially high in patients who consumed alcohol (defined as ≥400 g/mo), current smokers, and those with ≥20 pack-years of smoking. The risk was highest in subjects who had all of these characteristics (relative risk, 4.12); these patients had to stop smoking for 2 decades to reduce their risk level to that of never-smokers.Smoking has been calculated to attribute 25% of the risk for CP, and continued smoking after a diagnosis accelerates disease progression.45Talamini G. Bassi C. Falconi M. et al.Smoking cessation at the clinical onset of chronic pancreatitis and risk of pancreatic calcifications.Pancreas. 2007; 35: 320-326Crossref PubMed Scopus (17) Google Scholar Physicians often focus on counseling patients with CP against alcohol consumption and underestimate the role of smoking,46Yadav D. Slivka A. Sherman S. et al.Smoking is underrecognized as a risk factor for chronic pancreatitis.Pancreatology. 2010; 10: 713-719Abstract Full Text PDF PubMed Scopus (17) Google Scholar thereby missing opportunities to counsel patients on smoking cessation or to refer them to behavior modification programs.The relationship between smoking and pancreatic cancer has been studied extensively; there are nearly 500 references listed in PubMed on this association. Studies have consistently confirmed the relationship between smoking and pancreatic cancer, with smokers having about a 2-fold excess risk compared with nonsmokers. This increase in risk is smaller than for lung cancer but is similar to that of other tumors such as bladder cancer. This could be because the bladder and pancreas each have indirect exposure to tobacco carcinogens.A recent pooled analysis of 12 case-control studies that included nearly 13,000 patients with pancreatic cancer concluded that current smokers had an odds ratio of 2.2 compared with never smokers.47Bosetti C. Lucenteforte E. Silverman D.T. et al.Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4).Ann Oncolo