To the best of our knowledge, we demonstrated for the first time that patients with mild hyperlipasemia (60–79 U/L) showed five times higher risk of having IPMN compared to those with borderline hyperlipasemia. Moreover, patients with mild hyperlipasemia who need to take H2-blockers showed the highest risk of having IPMN. Therefore, further investigation with MRCP should be considered for patients with mild hyperlipasemia, especially when they had episodes of epigastric discomfort, to find high risk patients for future pancreatic carcinoma.
The prevalence of IPMN is rarely reported. IPMN was found in 6.6% who underwent MRI or CT [21, 22]. Our study showed higher prevalence of IPMN (22%), probably because all of our patients showed elevated lipase values at least once during one year. Moreover, the proportion of IPMN among all the pancreatic cystic lesions (IPMN and cysts) was greatly higher in our study (57%) than previously reported (31–35%) . Thus, our study indicates that hyperlipasemia is useful in identifying patients with IPMN.
We found for the first time that patients with mild hyperlipasemia showed higher prevalence of IPMN (36%) compared to those with borderline hyperlipasemia (17%). One possible mechanism is that IPMN might cause subclinical pancreatitis. Subclinical pancreatitis has been described in patients with isolated increases in serum lipase/amylase levels but with no symptoms or imaging features . IPMN is a well-known etiology for acute pancreatitis [13, 24–26], which occurs in about 12–67% of IPMN. Pancreatitis might be caused by hypersecretion of mucin and temporary obstruction of the pancreatic duct in IPMN, which causes elevation of pancreatic enzymes. Acute pancreatitis from IPMN might be unrecognized because typically acute pancreatitis from IPMN is predominantly mild and recurrent, with a long-standing asymptomatic hyperlipasemia [26, 27]. Thus, serum lipase is a better indicator of pancreatic inflammation than clinically defined pancreatitis , and we hypothesize that patients with IPMN may suffer subclinical inflammation of pancreas which causes hidden increase of serum lipase level, although episodes of acute pancreatitis were unrecognized in the past.
Another possible mechanism is that functional pancreatic disorder should be underlined. Functional pancreatic disorder is characterized by recurrent episodes of epigastric discomfort with elevated lipase/amylase without any causes of pancreatitis (e.g. alcohol, gallstones) [28, 29]. We formerly demonstrated that patients with unknown cause of dyspepsia had hyperlipasemia, which indicates that patients with unknown cause of dyspepsia may suffer from mild functional pancreatic disorders . Associated symptoms of IPMN were epigastric discomfort (50–70%) and weight loss (20–40%) in the previous reviews [1, 10]. Our report was consistent with these reviews that 55% of IPMN patients were taking medications for epigastric discomfort (H2-blckers, PPI, or camostat mesilate) and 30% of IPMN patients showed weight loss, which were higher than those without IPMN. Patients with weight loss or who need to take H2-blockers might have higher risk of IPMN.
Moderate hyperlipasemia above 80 U/L did not show any increased risk of IPMN in our study. Hyperlipasemia is known to be associated with non-pancreatic disorders such as inflammation or obstruction of biliary tract or gastrointestinal tract, and renal insufficiency [19, 20]. Interestingly, more than half of the patients (54%) with moderate hyperlipasemia had some causes which can explain their increased lipase values (e.g. gallstones), whereas less than one-third of patients (29%) with mild hyperlipasemia had any causes. As higher the lipase, the more patients had explainable causes for their lipase elevation, which may explain our findings. Thus, patients without any explainable causes of elevation in lipase should be monitored carefully.
Men and women were equally affected, elderly subjects aged 70th were frequently affected, and many of the cases were multifocal and located in the head of the pancreas in our study, which was consistent with the former studies [1–3]. Smoking and drinking were not associated with the risk of IPMN. The new finding is that liver cysts frequently coexist with IPMN in our study. Previous report showed that extra pancreatic cysts were frequent in patients with pancreatic cystic lesions , which may explain our result.
It is unknown whether patients with hyperlipasemia should undergo imaging examinations such as MRCP to detect pancreatic abnormalities. A former study showed that only 15% of patients with hyperlipasemia had pancreatic diseases , whereas another study showed half of the patients had pancreatic findings by MRCP [32, 33]. Our study showed that one-third of the patients had IPMN and more than half of the patients had pancreatic cystic lesions among patients with mild hyperlipasemia. Thus, patients with hyperlipasemia should be assessed in order to diagnose pancreatic diseases [16, 33]. Furthermore, there should be a debate whether IPMN should have been found in asymptomatic stage, as asymptomatic patients had a lower risk of progression to malignancy . It is known, however, that hyperlipasemia in patients with IPMN increase the risk of malignancy and showed poor prognosis [4, 7, 8]. Thus, our patients should have high risk of malignancy of the pancreas. Further study is warranted to clarify whether IPMN with hyperlipasemia should be diagnosed in asymptomatic stage for the better prognosis.
Several limitations should be mentioned. First, the number of patients was rather small to show whether hyperlipasemia is a marker of IPMN. However, there is no data at all to show the prevalence of IPMN in patients with hyperlipasemia, and this is the first study to show that one-third of patients with mild hyperlipasemia had IPMN. Further study with larger number of patients is needed. Second, we could not show the increasing risk of IPMN by increasing level of serum lipase. This might be explained by that greater lipase level can be explained by non-pancreatic disorders such as gallstones, which should be confirmed in another study.