Elsevier

Pancreatology

Volume 16, Issue 5, September–October 2016, Pages 893-899
Pancreatology

Original article
Predictive value of low serum pancreatic enzymes in invasive intraductal papillary mucinous neoplasms

https://doi.org/10.1016/j.pan.2016.06.663Get rights and content

Abstract

Background

Despite evidence suggesting a role of chronic pancreatitis in pancreatic carcinogenesis, its relationship with invasive intraductal papillary mucinous neoplasms (IPMN) remains unclear. Low levels of pancreatic enzymes are predictive markers of advanced chronic pancreatitis. We investigated whether low pancreatic enzyme levels were associated with a higher incidence of invasive IPMN.

Methods

This study included 146 consecutive patients who underwent surgical resection of IPMN between April 2001 and October 2014. Multivariable logistic regression analysis was conducted to assess the association between serum pancreatic enzymes and the incidence of invasive IPMN, with adjustment for clinical characteristics including alcohol consumption. The association of serum pancreatic enzymes with pathological pancreatic atrophy and inflammation in areas adjacent to or distant from the tumor was also evaluated.

Results

Low serum levels of pancreatic amylase and lipase were associated with a higher incidence of invasive IPMN (multivariable odds ratio [OR] = 9.6, 95% confidence interval [CI] = 2.99 to 35.1, P = 0.0001; OR = 14.2, 95% CI = 2.77 to 112, P = 0.001, respectively). Low serum pancreatic amylase and lipase levels were also associated with higher grade pancreatic atrophy in areas adjacent to the tumor (P = 0.011 and P = 0.017, respectively) and in areas distant from the tumor (P = 0.0002 and P = 0.001, respectively). Furthermore, low serum pancreatic amylase and lipase levels were associated with higher grade inflammation in areas distant from the tumor (P < 0.0001 and P = 0.001, respectively).

Conclusions

Low serum pancreatic enzymes may be a predictive marker of invasive IPMN. Excessive alcohol consumption did not influence the association of low pancreatic enzyme levels with invasive IPMN.

Introduction

There is accumulating evidence that the later stages of chronic pancreatitis may be associated with an increased risk of pancreatic cancer [1], [2]. Pancreatic parenchymal atrophy and inflammation are thought to be risk factors for tumor development [3], [4], [5]. However, whether chronic pancreatitis is associated with malignant intraductal papillary mucinous neoplasms (IPMN) has not been fully clarified.

IPMNs are a well-characterized group of intraductal mucin-producing cystic neoplasms of the pancreas with malignant potential [6], [7], [8], [9]. In recent guidelines, the high-risk signs of IPMN have been proposed mainly on the basis of imaging studies [10], [11], [12]. However, the inflammatory and atrophic status of pancreatic tissue is not considered as a risk factor for malignant IPMN in these guidelines. It has been reported that intestinal type IPMN, a specific histologic subtype of IPMN, is likely to be associated with severe atrophy and fibrosis of the surrounding parenchyma and mucous lake formation [13]. Another study revealed an association between the formation of pancreatic stones and IPMN [14]. Excessive alcohol consumption or hypersecretion of mucin by IPMN may induce chronic pancreatitis, which might be associated with the malignant transformation of these tumors [7], [15], [16].

Serum levels of pancreatic enzymes, such as pancreatic amylase and lipase, reflect the background state of the pancreas [17]. Low levels of pancreatic enzymes are associated with advanced chronic pancreatitis, and are also associated with pancreatic atrophy. Patients with pancreatic atrophy are known to have a higher risk of developing malignant tumors [18], [19]. Therefore, we investigated whether low serum levels of pancreatic enzymes were associated with a higher incidence of invasive IPMN. To test this hypothesis, we utilized a database of 146 consecutive patients who underwent surgical resection of IPMN at Kobe University Hospital, and examined the association of pancreatic enzymes with the incidence of invasive IPMN.

Section snippets

Study design

This study included 146 consecutive patients who underwent surgical resection of IPMN between April 2001 and October 2014. Patients with concomitant pancreatic carcinoma (N = 16) were excluded, with concomitant carcinoma being defined by discontinuous presence of both pancreatic carcinoma and IPMN. Patients with stenosis of the main pancreatic duct due to mass formation by invasive IPMN were also excluded (N = 3). We prospectively collected the following information preoperatively: age, body

Patient characteristics with respect to serum pancreatic amylase and lipase levels

We categorized the 142 IPMN patients by clinical features and factors associated with serum pancreatic amylase and lipase. Clinical features and laboratory data are summarized with respect to the serum levels of pancreatic amylase and lipase in Supplemental Tables 1 and 2. The pancreatic amylase and lipase levels were categorized as follows: serum amylase, normal (16–52 IU/l), high (>52 IU/l), and low (<16 IU/l); serum lipase, normal (16–60 IU/l), high (>60 IU/l), and low (<16 IU/l). There were

Discussion

The present study demonstrated that low serum levels of pancreatic enzymes were associated with a higher incidence of invasive IPMN. To the best of our knowledge, this was the first study to examine the association between invasive IPMN and serum levels of pancreatic enzymes in relation to histological changes of the background pancreas, which often shows parenchymal atrophy and inflammatory cell infiltration in these patients.

Serum levels of pancreatic enzymes are the most reliable markers

Grant support

This work was supported by JSPS KAKENHI (Grants-in-Aid for Scientific Research), Grant no. 15624848 (A.M.) and Grant no.15612795 (H.K.). This work was also supported by funds from the Research Committee of Intractable Pancreatic Diseases provided by the Ministry of Health, Labour, and Welfare of Japan (A.M., H.S., H.K.).

Disclosures

The authors have no conflicts of interest.

Author contributions

Y.Y. collected and analysed the data, and wrote the paper. A.M. designed the study concept, analysed the data, and wrote the paper. Y.Z. collected and analysed the data (pathological evaluation). M.T., K.S., H.S., T.K., T.N. and K.Y. collected and analysed the data. H.T., N.H., M.Y., Y.A., Y.O., H.K., T.F., Y.K. and T.A. were involved in study supervision and revised the paper.

Acknowledgement

We would like to thank the staff of the Center of Clinical Research (Dr. Omori) at Kobe University Hospital for their valuable contributions (advice on statistical analysis).

References (24)

  • J. Retter et al.

    Acute recurrent pancreatitis curtaining an intraductal papillary mucinous tumor of the pancreas

    J Gastrointest Liver Dis

    (2007)
  • G. Kloppel

    Clinicopathologic view of intraductal papillary-mucinous tumor of the pancreas

    Hepato Gastroenterol

    (1998)
  • Cited by (0)

    View full text