Search

Background: Alcohol consumption causes an estimated 4% of the global disease burden, prompting governments to impose regulations to mitigate the adverse effects of alcohol. To assist public health leaders and policymakers, the authors developed a composite indicator-the Alcohol Policy Index-to gauge the strength of a country's alcohol control policies., Methods and Findings: The Index generates a score based on policies from five regulatory domains-physical availability of alcohol, drinking context, alcohol prices, alcohol advertising, and operation of motor vehicles. The Index was applied to the 30 countries that compose the Organization for Economic Cooperation and Development and regression analysis was used to examine the relationship between policy score and per capita alcohol consumption. Countries attained a median score of 42.4 of a possible 100 points, ranging from 14.5 (Luxembourg) to 67.3 (Norway). The analysis revealed a strong negative correlation between score and consumption (r = -0.57; p = 0.001): a 10-point increase in the score was associated with a one-liter decrease in absolute alcohol consumption per person per year (95% confidence interval, 0.4-1.5 l). A sensitivity analysis demonstrated the robustness of the Index by showing that countries' scores and ranks remained relatively stable in response to variations in methodological assumptions., Conclusions: The strength of alcohol control policies, as estimated by the Alcohol Policy Index, varied widely among 30 countries located in Europe, Asia, North America, and Australia. The study revealed a clear inverse relationship between policy strength and alcohol consumption. The Index provides a straightforward tool for facilitating international comparisons. In addition, it can help policymakers review and strengthen existing regulations aimed at minimizing alcohol-related harm and estimate the likely impact of policy changes.

Objective: To systematically review trends in the epidemiology of the first attack of acute pancreatitis (AP) based on reported population-based studies., Methods: From Medline, we retrieved 18 full-length English language peer-reviewed original articles published from 1966 to June 2005 with population-based information on the epidemiology of first-attack AP. Trends over time were analyzed based on study- and country-specific data and the study site (UK vs non-UK)., Results: Eight studies were from the UK and 10 from other European centers. An increase in the annual incidence per 100,000 for first-attack AP was reported in 10 of 12 studies with longitudinal data from 4 countries (UK, Sweden, Denmark, and Netherlands). The overall AP incidence seems to be higher in non-UK studies compared with that of UK, partly explained by a higher incidence of alcoholic pancreatitis in non-UK studies. A linear trend for increase in gallstone pancreatitis incidence over time was observed irrespective of the study site (UK or non-UK). The AP incidence and mortality increased with age. Gallstone pancreatitis was more common in female subjects, and alcoholic pancreatitis was more common in middle-aged male subjects. The AP case fatality (%) has decreased over time, but the overall population mortality rate per 100,000 has remained unchanged. Recurrence after the first attack is milder with a substantially lower mortality., Conclusions: The incidence of AP seems to be increasing. Differences in the incidence and etiology between and within countries reflect differences in the risk factor prevalence. Case-fatality rate, but not the population-based mortality rate, decreased over time.

Objectives: Chronic pancreatitis is usually caused by heavy alcohol intake and, in many studies, also smoking. Because heavy drinkers usually smoke, making it difficult to separate the effects of these 2 factors, we thought to study the impact of smoking on the progression of nonalcoholic idiopathic chronic pancreatitis (ICP) METHODS: We used data from 83 patients with ICP in Switzerland and from 83 patients in Italy. We studied the impact of smoking on progression of disease as measured by the appearance of calcification and diabetes using Cox regression models., Results: In both centers, the prevalence of smoking was significantly higher in patients with ICP than in the background population. In Italian patients, smoking increased the risk of pancreatic calcifications (hazard ratio = 2.09; 95% confidence interval, 1.07-4.10). Smoking also shortened the time to appearance of calcification. Heavy smoking (>20 cigarettes per day) was associated with the appearance of diabetes (hazard ratio = 3.94; 95% confidence interval, 1.14-13.6). For those patients who never reported consuming alcohol, smoking remains a significant risk factor., Conclusions: In nonalcoholic ICP, smoking is associated with disease progression as measured by the appearance of pancreatic calcification and, to a lower extent, of diabetes. These findings were chiefly observed in patients who were older than 35 years at the time of onset of disease.

Pancreas cancer is considered an 'orphan' cancer because of its relative low incidence. Unfortunately even with early diagnosis, mortality rates are high, explaining why, despite the low incidence, it ranks eighth in a world listing of cancer mortality. International incidence rates vary in different countries, implying that environmental factors are important. Of these factors, smoking is the most well documented etiologic agent, explaining about 25% of all cases. Dietary factors may be important, but it has been difficult to define specific items which either increase or decrease the risk of pancreatic cancer. Since the incidence of pancreas cancer is so strongly age-dependent, we can anticipate an increasing number of patients as the population of most Western countries ages.

Previous reports suggest that allergic disorders may protect against various types of cancer, but the association between history of allergy and pancreatic cancer risk has not been well studied. We did a systematic review and meta-analysis of published studies to evaluate the association of any type, and specific types, of allergy and the risk of pancreatic cancer. We did a comprehensive literature search using MEDLINE, PUBMED, and the ISI Web of Science databases to identify potential relevant case-control and cohort studies. Pooled relative risks (RR) and 95% confidence intervals (95% CI) were calculated using the fixed- and random-effects model. Fourteen population-based studies (4 cohort and 10 case-control studies) with a total of 3,040 pancreatic cancer cases fulfilled our inclusion criteria. A history of allergy was associated with a reduced risk of pancreatic cancer (RR, 0.82; 95% CI, 0.68-0.99). The risk reduction was stronger for allergies related to atopy (RR, 0.71; 95% CI, 0.64-0.80), but not for asthma (RR, 1.01; 95% CI, 0.77-1.31). There was no association between allergies related to food or drugs and pancreatic cancer (RR, 1.08; 95% CI, 0.74-1.58). Overall, there was no evidence of publication bias. Allergies, in particular those related to atopy, seem to be associated with a decreased risk of pancreatic cancer. The hyperactive immune system of allergic individuals may, therefore, in some way lead to increased surveillance and protect against pancreatic cancer development.

In the United States, the cumulative mortality or lifetime risk of dying from pancreatic cancer is about 1-2%, but although this form of cancer is rare, nearly all patients die from the disease within one to two years. Because of its lethality, pancreatic cancer now ranks fourth as a cause of death from cancer. There are country-specific differences in rates, perhaps explained by differences in life-style factors or diet. African-Americans in the USA have rates that are about 50% higher than Caucasians. Smoking is the major known risk factor for this cancer, explaining 20-30% of all cases. Another 5-10% of causes are caused by germline mutations, with mutations in BRCA2 being the most frequent. Two background diseases increase the risk of pancreatic cancer-pancreatitis, and diabetes. Major challenges presented by this cancer are: 1) determination of the molecular pathways that make this cancer so aggressive; 2) development of new modalities, perhaps based on proteomics, to enhance early detection.

In the United States, acute pancreatitis, chronic pancreatitis, and pancreatic cancer are the most common pancreatic disorders requiring diagnosis and treatment. Pancreatic cancer is responsible for nearly 30,000 annual deaths and is the second most common cause of death from any type of gastrointestinal disease. Gallstone disease, which is strongly associated with obesity, and excessive consumption of alcohol are the major risk factors for benign pancreatic disease, whereas smoking is the most important factor known to cause pancreatic cancer. Therefore, to reduce the overall burden of pancreatic disease, we should focus on the control of three lifestyle factors: smoking, drinking, and obesity.

Molecular analyses have demonstrated mutations in the K-ras gene at codon 12 in the majority of pancreatic ductal adenocarcinomas (PDACs). In order to determine whether the K-ras mutation rate increases parallel to the grade of dysplasia in duct lesions, we performed a meta-analysis of the studies published between 1988 and 2003 that provide information on K-ras mutations in hyperplastic and dysplastic duct lesions in the pancreas. The described duct lesions were reclassified according to the nomenclature for pancreatic intraepithelial neoplasia (PanIN), and the molecular methods for detecting K-ras were reviewed. In PanIN lesions from pancreata of patients with PDAC, there was a stepwise increase in K-ras mutations that correlated with the grade of dysplasia of the PanIN lesion. K-ras mutations were found in 36%, 44%, and 87% of PanIN-1a, 1b, and 2-3 lesions, respectively (trend statistic P <.001). Mutation-enriched polymerase chain reaction (PCR) resulted in higher rates of K-ras mutations in PanIN than plain PCR did. The incidence of K-ras mutations in PanIN lesions associated with chronic pancreatitis (CP) or normal pancreas was low (around 10%). In CP, K-ras mutations were only found after a disease duration of 3 years. The correlation of the incidence of K-ras mutations with the grade of dysplasia in PanIN and the occurrence of these mutations in CP with a duration of more than 3 years underlines the importance of this genetic change for the development of PDAC.

Background & Aims: Cystic fibrosis (CF) results from abnormal production of sticky mucus, which obstructs many organs. In most cases, the pancreas is severely compromised, but 10%-15% of patients with CF have pancreas sufficiency (PS) and are subject to develop pancreatitis. The aim of this study is to determine which specific genotypes lead to the development of pancreatitis in patients with CF., Methods: We used prospective data collected by the Cystic Fibrosis Foundation and performed a nested case-control study with all patients who reported at least 1 episode of pancreatitis constituting the cases. We used logistic regression to assess the association between pancreatitis and genotype and the Kaplan-Meier method to estimate the cumulative incidence of pancreatitis for selected genotypes., Results: Three hundred sixty-four of 17,871 genotyped patients with CF (2.0%) reported at least 1 episode of pancreatitis. Only 0.9% of 12,997 patients with genotypes generally associated with pancreas insufficiency reported pancreatitis against 11.9% of 868 patients carrying at least 1 mild CF mutation generally associated with PS. The greatest rate of pancreatitis (19.0%) was observed for patients carrying an R334W mutation: 48% of these 79 patients were Hispanic and 13 patients were living in Puerto Rico., Conclusions: Of all patients with CF, those carrying an R334W mutation have the greatest risk for developing pancreatitis. This mutation is found mostly in Hispanic patients with CF living in Puerto Rico. There are no current data to determine whether asymptomatic carriers of the R334W mutation are at greater risk for developing pancreatitis or whether this mutation is frequent in Hispanics with idiopathic pancreatitis.

Pancreatic cancer is an uncommon tumor, but because the mortality rate approaches 100%, this form of cancer has now become a common cause of cancer mortality. In the United States it is the fourth most frequent cause of cancer mortality; in Japan it ranks as the fifth commonest cause of death from cancer. Smoking is the major known risk factor for pancreatic cancer, accounting for approximately 25-30% of all cases. Some of the time-dependent changes in the frequency of pancreatic cancer can be explained by smoking trends. Aggressive public health measures to control smoking would substantially reduce the burden of pancreatic cancer. Dietary factors are less important for pancreatic cancer than for other digestive tract tumors, but consumption of a diet with adequate quantities of fruits and vegetables, plus control of calories either by dietary measures or by exercise will help to prevent this lethal tumor. There are more than a dozen inherited germline mutations that increase the risk of pancreatic cancer. Of these, hereditary pancreatitis confers the greatest risk, while BRCA2 mutations are the commonest inherited disorder. In addition to germline defects, there are several common polymorphisms in genes that control detoxification of environmental carcinogens that may alter the risk of pancreatic cancer. More research will be needed in this area, to explain and to clarify the interaction between genes and environmental factors.

Background & Aims: Approximately 10% of pancreatic cancers are inherited, but the factors that affect tumorigenesis in familial pancreatic cancer are unknown. We sought to determine whether smoking or other factors could predict cancer risk in familial pancreatic cancer kindreds., Methods: We conducted a nested case-control study including 251 members of 28 families. All families included 2 or more members with pancreatic cancer. We determined the effects of smoking, young age of onset within the family, diabetes mellitus, sex, and number/standing of affected relatives on the risk of pancreatic cancer., Results: Smoking was an independent risk factor for familial pancreatic cancer (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.8-7.6), and the risk was greatest in males and subjects younger than 50 (OR, 5.2 and OR, 7.6, respectively). Smokers developed cancer 1 decade earlier than nonsmokers (59.6 vs. 69.1 years; P = 0.01), and the number of affected first-degree relatives also increased risk (OR, 1.4; 95% CI, 1.1-1.9 for each additional family member). Diabetes was not a risk factor for pancreatic cancer, although diabetes was associated with pancreatic dysplasia. One third of families demonstrated genetic anticipation, as the mean age of onset decreased by 2 decades between generations., Conclusions: Smoking is a strong risk factor in familial pancreatic cancer kindreds, particularly among males and those under age 50. Persons with multiple affected first-degree relatives are also at increased risk. These factors may be useful in selecting candidates for pancreatic cancer screening. Members of families with multiple pancreatic cancers should be counseled not to smoke.

Background: Cancer in patients with cystic fibrosis (CF), the most common genetic disorder in Caucasians, has been a rare event. However, more patients now reach adulthood, and more patients undergo organ transplantation-factors associated with an increased cancer risk. Our aim was to assess the risk of cancer in nontransplanted and transplanted CF patients., Methods: We followed 28 858 patients whose data were reported to the Cystic Fibrosis Foundation patient registry from 1990 through 1999 and compared the number of cancers observed in transplanted and nontransplanted patients to the number expected from population-based cancer incidence data. All statistical tests were two-sided., Results: In 202 999 person-years of observation of nontransplanted CF patients, 75 cancers were observed, but 69.7 were expected (standardized incidence ratio [SIR] = 1.1, 95% confidence interval [CI] = 0.8 to 1.4). Twenty-three digestive tract tumors were observed, but 4.5 were expected (SIR = 5.1, 95% CI = 3.2 to 7.6). More cancers than expected were observed of the small bowel, colon, and biliary tract but not of the stomach or rectum. We found that the deficit of non-digestive tract tumors was not statistically significant (52 observed versus 65.2 expected; SIR = 0.80, 95% CI = 0.6 to 1.0; P =.055). In 2725 person-years of observation of 1063 transplanted patients, 13 cancers were observed, but 2.05 were expected (SIR = 6.3, 95% CI = 3.4 to 10.8), and more digestive tract tumors (four observed versus 0.19 expected; SIR = 21.2, 95% CI = 5.8 to 54.2) and lymphomas (seven observed versus 0.16 expected; SIR = 44.0, 95% CI = 17.7 to 90.7) were observed than expected., Conclusions: We observed an increased risk of digestive tract cancers among adult CF patients, particularly of the small bowel, colon, and biliary tract. This increased risk appeared to be more pronounced in patients who had had an organ transplantation.

Patients on maintenance dialysis have increased risk for cancer, especially in the kidney and urinary tract. In a retrospective cohort of 831,804 patients starting dialysis during 1980 to 1994 in the United States, Europe, or Australia and New Zealand, standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated for kidney and bladder cancers. Risks for cancers of the kidney (SIR 3.6; CI 3.5 to 3.8) and bladder (SIR 1.5; CI 1.4 to 1.6) were increased, relatively more in younger than older patients and more in female patients (kidney: SIR 4.6, CI 4.3 to 4.9; bladder: SIR 2.7, CI 2.4 to 2.9) than male patients (kidney: SIR 3.2, CI 3.0 to 3.4; bladder: SIR 1.3, CI 1.2 to 1.3). SIR for kidney cancer were raised in all categories of primary renal disease, and for bladder cancer in all but diabetes and familial, hereditary diseases. Notably high SIR occurred in toxic nephropathies (chiefly analgesic nephropathy) and miscellaneous conditions (a category that includes Balkan nephropathy), the excess of kidney cancer in these conditions being urothelial in origin. SIR for kidney cancer rose significantly, and those for bladder cancer fell (not reaching significance) with time on dialysis. There was no association with type of dialysis. The pattern of increased risk for renal parenchymal cancer in dialysis patients is consistent with causation through acquired renal cystic disease and of urothelial cancers of the kidney and bladder with the carcinogenic effects of certain primary renal diseases.

The fate of a patient with acute pancreatitis largely depends on early recognition of the severity of the disease. Acute pancreatitis is severe when organ failure and/or pancreatic necrosis occur. Whereas simple and low cost parameters are available for the detection of organ failure, the detection and extent of pancreatic necrosis requires a costly contrast-enhanced computed tomography. This is not always available in all institutions. This review article which considers when the clinician should be concerned about his patient diagnosed with acute pancreatitis, summarizes possibilities for diagnosing clinical severe (that is organ failure) and radiological severe (that is the necrotizing form of the disease) pancreatitis using simple and inexpensive parameters which are available everywhere. At present, a CT scan should be performed in those patients with alcohol etiology, those admitted to hospital early (time interval between the onset of symptoms and admission to hospital of less than 24 h, those presenting with rebound tenderness and/or guarding, a lipase >1,000 U/l, as well as a raised hematocrit and blood glucose. The evaluation, furthermore, shows that some parameters have a sufficiently high negative predictive value of >90%, which may render a contrast-enhanced CT scan unnecessary in the early stages, unless the patient fails to improve. These parameters include non-alcohol etiology, time interval between onset and admission to hospital longer than 24 h, no guarding or rebound tenderness on admission, low or normal hematocrit and nonelevated blood glucose. It is necessary to look further on simple low cost and more valid parameters on admission in order to reliably distinguish between necrotizing pancreatitis and interstitial pancreatitis., (Copyright 2003 S. Karger AG, Basel and IAP)

Objective: Since pancreatic cancer is one of the most rapidly fatal cancers, prevention is of paramount importance to reduce the future burden of this disease. We studied the impact of ceasing smoking on the future incidence of pancreatic cancer in the European Union (EU)., Methods: We developed a computer simulation model, Markov multi-state type, using country-specific published data on population sizes, smoking behaviour, pancreatic cancer incidence and total mortality rates, corresponding relative risks for ex- and current smokers, and estimated probabilities of starting and ceasing smoking (transition rates), with which we refined previously reported preliminary results. We simulated a scenario based on theoretically maximal smoking reduction, a more feasible scenario based on the World Health Organization's 'Health for All' target in which smoking prevalence is reduced to 20% in 2015, and scenarios based on reductions in smoking prevalence in 20 steps of 5% (from 0% to 100% reduction) in 2015. Simulations were based on changes in transition rates for smoking behaviour. We estimated the absolute and relative reduction of pancreatic cancer patients in the EU, for each scenario compared to a reference scenario in which the current transition rates remained unchanged, for the period 1994-2015., Results: Theoretically, if all smokers would quit instantly, the estimated number of new pancreatic cancer patients up to 2015 in the EU could be reduced by 15% (around 150 000 patients). The more feasible scenario would lead to a reduction of almost 29 500 male and 9500 female patients. These results corresponded to a reduction in smoking prevalence with around 45% and 30% among men and women, respectively, in each EU country., Conclusion: Giving up smoking would substantially reduce the future incidence of pancreatic cancer. This emphasizes the importance of prevention in the reduction of the future pancreatic cancer burden.

Background: The etiology of tumors arising in the biliary tract remains unclear. Several previous studies have detected Helicobacter pylori organisms in bile from patients with gallstones or cholecystitis. The objective of this study was to determine whether there is an association between H. pylori in bile and biliary tract carcinoma., Methods: The authors used polymerase chain reaction (PCR) assays to detect the presence of H. pylori in the stomach and bile from 89 patients: Sixty-three disease free patients had biliary calculi, 15 patients had carcinoma of the biliary tract, and 11 patients had neither gallstones nor carcinoma. Bile was considered to contain H. pylori only if the results of PCR determinations were positive in two or more samples assayed independently in two separate laboratories., Results: There was a strong association between the presence of H. pylori in the stomach and in the bile (P < or = 0.01). Biliary H. pylori was associated with age but not with gender, and it was associated strongly with the clinical diagnosis. Patients with gallstones were 3.5 times as likely to have H. pylori in the bile compared with patients in a control group (95% confidence interval [95%CI], 0.8-15.8; P = 0.100), and H. pylori was 9.9 times more frequent in patients with biliary tract carcinoma compared with patients in the control group (95%CI, 1.4-70.5; P = 0.022)., Conclusions: There is a strong association between biliary tract carcinoma and H. pylori in bile. If these results are confirmed by prospective studies, H. pylori may be responsible for a significant proportion of malignant biliary tract disease., (Copyright 2002 American Cancer Society.)

Introduction: The APACHE II score is highly recommended worldwide for the assessment of severe pancreatitis (interstitial and necrotizing), and a score of at least eight points on admission to the hospital is said to indicate severe pancreatitis., Aim: To evaluate this assumption and to check whether an APACHE II score of at least eight points really indicates necrotizing pancreatitis as shown by contrast-enhanced computed tomography (CT)., Methodology: This study included 326 patients with a first attack of acute pancreatitis and is part of a prospective study on the natural course of acute pancreatitis. All patients underwent contrast-enhanced CT within 72 hours of admission. The following parameters for the severity of the disease were used: respiratory and renal failure according to the Atlanta classification; indication for dialysis, ventilation, and surgery; time spent in intensive care unit and total hospital stay; Ranson score adjusted for cause; Imrie score; and Balthazar score (CT)., Results: Of the 326 patients, 262 (80%) had interstitial pancreatitis and 64 (20%) had necrotizing pancreatitis. In 74 (28%) of the 262 patients with interstitial pancreatitis, the APACHE II score was at least eight points, indicating severe pancreatitis (overestimation of the disease), whereas the score was less than eight in 41 (64%) of 64 patients with necrotizing pancreatitis (underestimation). Sensitivity was 36%; specificity was 72%; the positive predictive value was 24%; and the negative predictive value was 82%., Conclusion: The evaluation of sensitivity, specificity, and positive and negative predictive value for all APACHE II score points showed that there was not a "golden" cutoff to detect necrotizing pancreatitis. We conclude that the APACHE II score on admission to the hospital is unreliable to diagnose necrotizing pancreatitis.

Ranking fourth as a cause of death from cancer for men and women in the United States, pancreatic cancer represents a significant challenge for physicians and surgeons. In addition to the elderly, high-risk groups include blacks, men, smokers, and patients with certain preexisting diseases such as pancreatitis and long-standing diabetes. Various inherited genetic disorders cause approximately 5% to 10% of the total cases of pancreatic cancer. Smoking doubles the risk of pancreatic cancer. Control of smoking offers the best available strategy for reducing the incidence of this disease. Dietary measures to reduce the risk of pancreatic cancer include maintenance of normal body weight and consumption of a well balanced diet with adequate amounts of fruits and vegetables. Chronic pancreatitis caused by heavy alcohol consumption or, rarely, by an underlying inherited disorder is another strong risk factor, but because this benign disease is uncommon, elimination of this underlying cause would have minimal impact on the frequency of pancreatic cancer.

Pancreatic cancer is the fourth leading cause of cancer deaths in the USA in both sexes. Early diagnosis is difficult and the overall mortality rate is high. Individuals at high risk for pancreatic cancer include smokers, and persons with all forms of chronic alcoholic, metabolic, tropical or hereditary pancreatitis. The duration of exposure to inflammation seems to be the major factor involved in the transition from benign to malignant condition. Smoking, which appears to further accelerate the carcinogenic transformation, remains the strongest risk factor amenable to preventive intervention., (Copyright 2002 S. Karger AG, Basel)