Periodontal disease, edentulism, and pancreatic cancer: a meta-analysis.

Background: Periodontal disease (PD), now our commonest infectious disorder leads to tooth loss, and has been linked to various systemic diseases, including various types of cancer. The aim of this study is to provide a systematic review and a meta-analysis of the relationship between PD, edentulism, and pancreatic cancer (PC). Patients and methods: From an initial review of 327 references we selected eight studies concerning periodontitis or edentulism with sufficient quantitative information to allow us to examine the risk of PC. We used relative risks (RRs), hazard ratios, or odds ratios to measure the association between periodontitis, edentulism, and PC. We employed random effects models to obtain summary risks, and we also provide measures of study differences and possible biases. Results: The summary RR for periodontitis and PC was 1.74 [95% confidence interval (CI) 1.41-2.15] and 1.54 for edentulism (95% CI 1.16-2.05). There was no evidence of heterogeneity for either variable, and no evidence of publication bias. The studies included reports from three continents, suggesting that the association is generalizable. Most of the studies were adjusted for variables thought to be associated with PC, such as gender, smoking, BMI, diabetes, and alcohol. Conclusions: Using meta-analysis, both periodontitis and edentulism appear to be associated with PC, even after adjusting for common risk factors. As yet, the mechanisms linking oral disease and PC are uncertain, but could be related to changes in the oral microbiome-an area of current research.

Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Pancreatitis is a known risk factor for pancreatic cancer; however, an unknown fraction of the disease is thought to be a consequence of tumor-related duct obstruction. PATIENTS AND METHODS: A pooled analysis of a history of pancreatitis and risk of pancreatic cancer was carried out considering the time interval between diagnoses and potential modification by covariates. Adjusted pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from 10 case-control studies (5048 cases of ductal pancreatic adenocarcinoma and 10,947 controls) taking part in the International Pancreatic Cancer Case-Control Consortium (PanC4). RESULTS: The association between pancreatitis and pancreatic cancer was nearly three-fold at intervals of >2 years between diagnoses (OR: 2.71, 95% CI: 1.96-3.74) and much stronger at intervals of ≤2 years (OR: 13.56, 95% CI: 8.72-21.90) probably reflecting a combination of reverse causation and antecedent misdiagnosis of pancreas cancer as pancreatitis. The younger (<65 years) pancreatic cancer cases showed stronger associations with previous (>2 years) pancreatitis (OR: 3.91, 95% CI: 2.53-6.04) than the older (≥65 years) cases (OR: 1.68, 95% CI: 1.02-2.76; P value for interaction: 0.006). CONCLUSIONS: Despite a moderately strong association between pancreatitis (diagnosed before >2 years) and pancreatic cancer, the population attributable fraction was estimated at 1.34% (95% CI: 0.612-2.07%), suggesting that a relatively small proportion of pancreatic cancer might be avoided if pancreatitis could be prevented.

Venous thromboembolic events and organ-specific occult cancers: a review and meta-analysis.

BACKGROUND: Despite a recognized association between venous thromboembolic events (VTE) and cancer, little is known about the strength and the features of this association. We performed a meta-analysis in order to clarify this issue. METHODS: We retrieved data from 40 reports published between 1982 and 2007: 12 contained cancer risk estimates for patients with either idiopathic or secondary VTE vs. subjects without VTE and 17 for patients with idiopathic vs. secondary VTE. We also pooled risk estimates from four cohort studies to assess the association between VTE and specific forms of cancer and conducted a proportional incidence study, based on the remaining 28 reports, which did not provide risk estimates. RESULTS: The pooled relative risk (RR) of cancer was 3.2 [95% confidence interval (95% CI) 2.4-4.5] for patients with any form of VTE vs. no VTE, 2.7 (95% CI 1.9-3.9) for patients with idiopathic vs. no VTE and 3.8 (95% CI 2.6-5.4) for patients with idiopathic vs. secondary VTE. In the pooled cohort studies, RRs for VTE vs. no VTE were significantly elevated for cancers of the ovary (RR 7.0), pancreas (RR 6.1), liver (RR 5.6), blood (4.2), brain (RR 3.8), kidney (RR 3.4), lung (3.1), colon (2.9), and esophagus (2.1). In the proportional incidence study, cancers of the pancreas, colon, and blood were significantly more frequently observed than in the general population. CONCLUSIONS: Overall we found a 3-fold excess risk of occult cancer in patients with VTE. The risk varies according to tumor site and is highest for cancers of the ovary, pancreas, and liver.

Cigarette smoking accelerates progression of alcoholic chronic pancreatitis.

BACKGROUND: Smoking is a recognised risk factor for pancreatic cancer and has been associated with chronic pancreatitis and also with type II diabetes. AIMS: The aim of this study was to investigate the effect of tobacco on the age of diagnosis of pancreatitis and progression of disease, as measured by the appearance of calcification and diabetes. PATIENTS: We used data from a retrospective cohort of 934 patients with chronic alcoholic pancreatitis where information on smoking was available, who were diagnosed and followed in clinical centres in five countries. METHODS: We compared age at diagnosis of pancreatitis in smokers versus non-smokers, and used the Cox proportional hazards model to evaluate the effects of tobacco on the development of calcification and diabetes, after adjustment for age, sex, centre, and alcohol consumption. RESULTS: The diagnosis of pancreatitis was made, on average, 4.7 years earlier in smokers than in non-smokers (p = 0.001). Tobacco smoking increased significantly the risk of pancreatic calcifications (hazard ratio (HR) 4.9 (95% confidence interval (CI) 2.3-10.5) for smokers v non-smokers) and to a lesser extent the risk of diabetes (HR 2.3 (95% CI 1.2-4.2)) during the course of pancreatitis. CONCLUSIONS: In this study, tobacco smoking was associated with earlier diagnosis of chronic alcoholic pancreatitis and with the appearance of calcifications and diabetes, independent of alcohol consumption.

Epidemiology of pancreatic diseases in Lüneburg County. A study in a defined german population.

BACKGROUND/AIMS: Worldwide, the incidence of pancreatic cancer is very well known, that of acute pancreatitis and chronic pancreatitis not. Our study sought to determine the incidence of all three pancreatic diseases in a well-defined population in Germany. METHODS: Records of all patients treated for acute (first attacks only) and chronic pancreatitis as well as pancreatic cancer from 1988 to 1995 and who resided in the county of Lüneburg were evaluated. RESULTS: The crude incidence rates for acute pancreatitis, chronic pancreatitis and pancreatic cancer per 100,000 inhabitants/year were 19.7, 6.4, and 7.8. In acute and chronic pancreatitis the male gender dominated, whereas in pancreatic carcinoma the gender ratio was almost even. Peak incidence for acute pancreatitis was in the age group of 35-44 years, for chronic pancreatitis 45-54, and for pancreatic cancer 65-75. Etiology of acute pancreatitis was biliary in 40%, alcohol abuse in 32%, unknown in 20%, and other in 8% of the patients. In chronic pancreatitis alcohol abuse was the etiology in 72% and unknown (idiopathic) in 28%. CONCLUSION: For the first time, epidemiological data obtained in a well-defined German population are being published relating to all three pancreatic diseases: acute pancreatitis (incidence rate, etiology and severity), chronic pancreatitis (incidence rate and etiology), and pancreatic carcinoma (incidence rate). A peak incidence of chronic pancreatitis occurring in an age group 10 years older than the peak age group for acute pancreatitis suggests that chronic pancreatitis develops during this time-frame following first attacks of acute pancreatitis.

Acute pancreatitis: does gender matter?

In a number of gastrointestinal and nongastrointestinal diseases, gender has been proven to be an independent risk factor for severity. To determine whether this holds true for severity in acute pancreatitis is the aim of our study. This paper derives from a prospective study on the epidemiology of acute pancreatitis, which included 274 patients (172 male and 102 female) with a first attack of the disease. Severity parameters were: Atlanta criteria (arterial Po2 < or = 60 mm Hg, and serum creatinine on admission >2 mg/dl after rehydration); Ranson's and Imrie's prognostic factors; APACHE II score; Balthazar-scored contrast-enhanced computed tomography (CT) results obtained within 72 hr of admission; days spent in the intensive care unit and total hospital stay; the necessity for artificial ventilation, dialysis, or surgery; and mortality. As already known, there is a significant association between gender and etiology of pancreatitis in general. Not surprisingly, the men in our study had alcohol-induced acute pancreatitis more frequently than women, whereas biliary pancreatitis predominated among the women. As for severity, there was no significant association between gender and any of the severity parameters with a few minor exceptions: longer hospital stays, higher Imrie scores and more pseudocysts for women, and more necroses in women with idiopathic pancreatitis. Thus, gender is no independent risk factor for the severity and outcome of acute pancreatitis.

Has blood glucose level measured on admission to hospital in a patient with acute pancreatitis any prognostic value?

BACKGROUND: Early detection of pancreatic necrosis allows better management of the disease. Contrast-enhanced computed tomography (CT) as the gold standard for detecting pancreatic necrosis is expensive. AIM OF THE STUDY: This study was to evaluate for the first time whether blood glucose estimation on hospital admission--a simple, cheap, readily available laboratory parameter--may detect pancreatic necrosis and have prognostic value in acute pancreatitis. METHODS: Single blood glucose estimation upon hospital admission was evaluated prospectively for detecting pancreatic necrosis and as a prognostic indicator. The study included 241 nondiabetic patients with a first attack of acute pancreatitis. All underwent CT within 72 h of admission. RESULTS: High blood glucose (> 125 mg/dl) correlated significantly with complex high clinical and biochemical prognostic scores (Ranson, Imrie), a high Balthazar score, pancreatic pseudocysts, and a long hospital stay, but not with organ failure, indication for artificial ventilation, dialysis, surgery, length of intensive care, and mortality. Pancreatic necrosis detection sensitivity of high blood glucose was 83%, specificity 49%, positive predictive value 28%, and negative predictive value 92%. CONCLUSION: A patient with normal blood glucose on admission is unlikely to have pancreatic necrosis. Contrast-enhanced CT would not be needed unless the patient fails to improve.

K-Ras mutations and benign pancreatic disease.

This review addresses the history of the ras oncogene, the techniques used to detect molecular alterations in the ras oncogene, and the application of polymerase chain reaction (PCR)-based methods to determine point mutations in clinical samples of patients with pancreatic diseases, namely pancreatic carcinoma and chronic pancreatitis. The frequency of ras mutations in pancreatic carcinoma is high, ranging from 70 to almost 100%. The frequence of ras mutations in chronic pancreatitis, either in pancreatic tissue or pancreatic secretions, vary between 0 and 100%. This wide range in part may be owing to differences in sampling, DNA extraction, or PCR method. The meaning of a k-ras mutation is under debate. Taking into account the positivity of ductal hyperplasias in normal pancreas and ras mutations in normal appearing duct cells, this molecular finding may not mean anything. In contrast, ras mutations are associated with smoking, one acknowledged risk factor for pancreatic carcinoma. The need for large prospective cohort studies is emphasized.

Risk factors for cancer in hereditary pancreatitis. International Hereditary Pancreatitis Study Group.

Hereditary pancreatitis is a rare form of pancreatitis, accounting for approximately 1% of all types of pancreatitis. It is inherited as an autosomal dominant disease, with incomplete penetrance. The genetic defect is believed to be caused by mutations in the trypsinogen gene. Patients who inherit the disorder suffer from a form of pancreatitis that resembles other types of pancreatitis, but the age of onset is much earlier. Sixteen biopsy-proven pancreatic cancers have developed in a cohort of 412 patients with a median follow-up period of 18 years (interquartile range, 7 to 30 years) since the onset of symptoms. Compared with the background population, the risk of pancreatic cancer is approximately 50 to 60 times greater than expected. Smoking appears to be an additional risk factor in these patients: Smoking increases the risk of developing pancreatic cancer and lowers the age of onset by approximately 20 years. Patients with hereditary pancreatitis are urged to avoid smoking because it greatly increases the risk of pancreatic cancer and to avoid alcohol, a known risk factor for all forms of pancreatitis.

Chronic pancreatitis and other risk factors for pancreatic cancer.

Pancreatic cancer is the fourth or fifth most common form of cancer in Western countries. Early diagnosis is difficult and the overall mortality rate is high. Individuals at high risk for pancreatic cancer include smokers, African-Americans, and persons with various types of pancreatitis. As with other cancers, dietary factors play an important role. Approximately 10% of all pancreatic tumors may be related to an inherited germ line disorder.

Pancreatico-biliary malignancy: prevalence and risk factors.

Tumors arising in the pancreatico-biliary system arise from the same embryological source and share several similar clinical features. For both sites, the mortality rate is high and early diagnosis is difficult. Despite these similarities, there are clear epidemiologic differences between cancers of the biliary tract and cancers of the pancreas. Gallbladder cancer is more frequent in females, whereas pancreatic cancer is more frequent in males. High-risk populations for gallbladder cancer include Native American Indians and Hispanic Americans. Black populations are at high risk for pancreatic cancer. Gallstones are causally related to gallbladder cancer, but for pancreatic cancer, smoking is the major known risk factor. The increasing frequency of cholecystectomy in persons with gallstones should result in a reduction in the incidence of gallbladder cancer. For pancreatic cancer, public health efforts to reduce smoking offers the best chance for prevention.