Pancreatic cancer is projected to become the leading cause of cancer deaths by 2050. The risk for pancreatic cancer may be reduced by up to 27% by modifying lifestyle risk factors, most notably tobacco smoking. Based on analysis of more than 2 million unselected individuals from general population, this article quantified the risk of pancreatic cancer in relation to lifelong tobacco smoking and alcohol consumption status, both alone and in combination. It also provided a state-of-the-art review of animal studies on the effect of tobacco smoke and alcohol on genetically engineered mouse models of pancreatic precursor lesions, as well as the role of immune microenvironment in pancreatic carcinogenesis activated by tobacco and alcohol.

Background & aims

Both liver disease (LD) and pancreatitis pose substantial burdens. There have been no general population-based studies on frequency of LD after an episode of pancreatitis. The aim of this study was to investigate the occurrence of LD in a population-based cohort of patients following pancreatitis.

Methods

Nationwide data on the general population of nearly 3 million people were used to identify retrospectively diagnoses of acute pancreatitis, chronic pancreatitis (CP), LD and cirrhosis from 1998 to 2016. Acute pancreatitis was categorised as first (FAP) or recurrent (RAP) episode. Number of pancreatitis recurrences prior to LD diagnosis was determined.

Results

A total of 20,931 pancreatitis patients were included, of which 874 developed LD following pancreatitis. The incidence of LD in FAP was 115.59 (95% confidence interval 102.19-128.98), in RAP - 217.63 (95% confidence interval 173.31-261.94), and in CP - 539.43 (95% confidence interval 494.72-584.13) patients per 100,000 pancreatitis patients per year. There was a significant increase in the probability of LD with increasing number of pancreatitis recurrences and, for the same number of pancreatitis recurrences, LD was significantly more frequent after CP than RAP (hazard ratio 1.666 (95% confidence interval 1.322-2.098; p = <0.001)).

Conclusions

The frequency of LD increases from FAP to RAP to CP. While number of pancreatitis recurrences is a significant risk factor for development of LD, there is a higher probability of LD following CP than RAP even for the same number of recurrences. Interventions preventing pancreatitis and its progression may lower the burden of LD.

Background

While the close morphological relationship between the exocrine and endocrine pancreas is well established, their functional interaction remains poorly understood. The aim of this study was to investigate the associations between circulating levels of pancreatic proteolytic enzymes and insulin, as well as other pancreatic hormones.

Methods

Fasting venous blood samples were collected and analyzed for trypsin, chymotrypsin, insulin, glucagon, somatostatin, and pancreatic polypeptide. Linear regression analysis was used in unadjusted and two adjusted (accounting for prediabetes/diabetes, body mass index, smoking, and other covariates) statistical models.

Results

A total of 93 individuals with a history of acute pancreatitis were included in this cross-sectional study. Chymotrypsin was significantly associated with insulin in the two adjusted models (p = 0.005; p = 0.003) and just missed statistical significance in the unadjusted model (p = 0.066). Chymotrypsin was significantly associated with glucagon in both unadjusted (p = 0.025) and adjusted models (p = 0.014; p = 0.015); as well as with somatostatin - in both unadjusted (p = 0.001) and adjusted models (p = 0.001; p = 0.002). Trypsin was not significantly associated with insulin in any of the models but was significantly associated with glucagon in both unadjusted (p < 0.001) and adjusted models (p < 0.001), and pancreatic polypeptide in both unadjusted (p < 0.001) and adjusted (p < 0.001) models.

Conclusion

The state of hyperinsulinemia is characterized by a dysfunction of the exocrine pancreas. In particular, chymotrypsin is increased in the state of hyperinsulinemia and trypsin is significantly associated with glucagon and pancreatic polypeptide.

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest types of cancer. The worldwide estimates of its incidence and mortality in the general population are eight cases per 100,000 person-years and seven deaths per 100,000 person-years, and they are significantly higher in the United States than in the rest of the world. The incidence of this disease in the United States is more than 50,000 new cases in 2017. Indeed, total deaths due to PDAC are projected to increase dramatically to become the second leading cause of cancer-related deaths before 2030. Considering the failure to date to efficiently treat existing PDAC, increased effort should be undertaken to prevent this disease. A better understanding of the risk factors leading to PDAC development is of utmost importance to identify and formulate preventive strategies. Large epidemiologic and cohort studies have identified risk factors for the development of PDAC, including obesity and type 2 diabetes mellitus. This review highlights the current knowledge of obesity and type 2 diabetes as risk factors for PDAC development and progression, their interplay and underlying mechanisms, and the relation to diet. Research gaps and opportunities to address this deadly disease are also outlined.