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Abstract

We thank Barkin, Freeman, and Barkin for their interest in our paper entitled “Acute Pancreatitis and Pancreatic Cancer Risk: A Nationwide Matched-cohort Study in Denmark.”1Kirkegard J. et al.Gastroenterology. 2018; 154: 1729-1736Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar Barkin et al raise some interesting hypotheses to extend our knowledge on the progression of acute pancreatitis to pancreatic cancer. Barkin et al propose that an alternative explanation to our findings could be that acute pancreatitis progresses to chronic pancreatitis and then pancreatic cancer, rather than a direct association between acute pancreatitis and pancreatic cancer. We agree with Barkin et al that this is an important pathway. However, we censored patients if they were diagnosed with chronic pancreatitis. This strategy would effectively mitigate any bias caused by the pathway proposed by Barkin et al. Therefore, the concerns raised by Barkin et al concerning the lack of information on the severity of acute pancreatitis, which could increase the rate of progression to chronic pancreatitis, is unlikely to explain our findings. Similarly, patients with recurrent biliary acute pancreatitis leading to chronic pancreatitis and later pancreatic cancer is also unlikely to have had a substantial impact on our estimate owing to the censoring at chronic pancreatitis diagnosis. Barkin et al also note that we saw the highest risk of pancreatic cancer in patients with idiopathic acute pancreatitis. However, as stated in the Discussion of our paper, we would like to point out the substantial uncertainty of the acute pancreatitis etiology based on our data sources. We can, therefore, not provide a reliable estimate of the number of biliary acute pancreatitis episodes before cholecystectomy was performed. Other histologic types, beside pancreatic adenocarcinomas, included small cell carcinomas, squamous cell carcinomas, neuroendocrine tumors, and cystic and sarcomatous tumors. Our findings were largely unaffected by the histology of the tumor. However, only around 60% of the cancers were registered as ductal adenocarcinomas, suggesting underreporting or misclassification. In addition, this number differed between patients with acute pancreatitis (59.6%) and comparison subjects (62.1%), which could compromise the interpretation of such analysis. However, we encourage other researchers to examine whether the association proposed in our study differs according to pancreatic cancer morphology. Regarding the concerns raised by Barkin et al on hypertriglyceridemia, we were unable to account for this factor, because we did not have information on laboratory data. However, high concentrations of triglycerides are needed to induce acute pancreatitis.2Berglund L. et al.J Clin Endocrinol Metab. 2012; 97: 2969-2989Crossref PubMed Scopus (512) Google Scholar The number of patients with such high levels is likely to be small3Ford E.S. et al.Arch Intern Med. 2009; 169: 572-578Crossref PubMed Scopus (163) Google Scholar and, therefore, to have had only a minimal impact on our estimates. We agree with Barkin et al that the actual association between acute pancreatitis, chronic pancreatitis, and pancreatic cancer is very complex and requires further investigation. Our article serves to improve our understanding of this complex topic. As shown previously,4Sankaran S.J. et al.Gastroenterology. 2015; 149: 1490-1500.e1491Abstract Full Text Full Text PDF PubMed Scopus (216) Google Scholar and as suggested by Barkin et al, the progression from acute pancreatitis to chronic pancreatitis is an important component in the association between acute pancreatitis and pancreatic cancer. However, our study suggests that there is an additional pathway from acute pancreatitis to pancreatic cancer. This subject should be investigated further, particularly with respect to the number of acute pancreatitis episodes and their etiology in addition to pancreatic cancer morphology. Is It Acute Pancreatitis or Recurrent Acute Pancreatitis Leading to Chronic Pancreatitis that Increases Pancreatic Cancer Risk?GastroenterologyVol. 155Issue 4PreviewWe read with great interest the article by Kirkegard et al entitled, “Acute Pancreatitis and Pancreatic Cancer Risk: A Nationwide Matched-cohort Study in Denmark.”1 Our present understanding is that acute pancreatitis (AP) leads to the development of chronic pancreatitis (CP), which is associated with an increased risk of pancreatic cancer (PC). This association of CP with PC was shown by the lead author of the present study, who found that CP increases the risk of PC, but the association diminishes with long-term follow-up. Full-Text PDF