Elsevier

Surgery

Volume 163, Issue 3, March 2018, Pages 600-605
Surgery

Pancreatic cyst fluid glucose: rapid, inexpensive, and accurate diagnosis of mucinous pancreatic cysts

https://doi.org/10.1016/j.surg.2017.09.051Get rights and content

Abstract

Background

The most widely accepted biochemical test for preoperative differentiation of mucinous from benign, nonmucinous pancreatic cysts is cyst fluid carcinoembryonic antigen. However, the diagnostic accuracy of carcinoembryonic antigen ranges from 70% to 86%. Based on previous work, we hypothesize that pancreatic cyst fluid glucose may be an attractive alternative to carcinoembryonic antigen.

Methods

Pancreatic cyst fluid was collected during endoscopic or operative intervention. Diagnoses were pathologically confirmed. Glucose and carcinoembryonic antigen were measured using a patient glucometer and automated analyzer/enzyme-linked immunosorbent assay. Sensitivity, specificity, accuracy, and receiver operator characteristic analyses were performed.

Results

Cyst fluid samples from 153 patients were evaluated (mucinous: 25 mucinous cystic neoplasms, 77 intraductal papillary mucinous neoplasms, 4 ductal adenocarcinomas; nonmucinous: 21 serous cystic neoplasms, 9 cystic neuroendocrine tumors, 14 pseudocysts, 3 solid pseudopapillary neoplasms). Median cyst fluid glucose was lower in mucinous versus nonmucinous cysts (19 vs 96 mg/dL; P < .0001). With a threshold of ≤ 50 mg/dL, cyst fluid glucose was 92% sensitive, 87% specific, and 90% accurate in diagnosing mucinous pancreatic cysts. In comparison, cyst fluid carcinoembryonic antigen with a threshold of >192 ng/mL was 58% sensitive, 96% specific, and 69% accurate. Area under the curve for glucose and CEA were similar at 0.91 and 0.92.

Conclusion

Cyst fluid glucose has significant advantages over carcinoembryonic antigen and should be considered for use as a routine diagnostic test for pancreatic mucinous cysts.

Introduction

Pancreatic cancer will be diagnosed in 53,670 Americans and will take the lives of 43,090 in 2017.1 Current available treatment strategies offer little chance for cure and a limited extension of life. In light of the low long-term survival rates after pancreatic cancer diagnosis, optimal clinical management should include prevention strategies. A unique opportunity for prevention of pancreatic cancer exists in specific high-risk populations such as patients with precancerous pancreatic cysts. Although as many as 2% to 3% of American adults are found to have pancreatic cysts on routine cross-sectional imaging, not all cysts have malignant potential and undergo malignant transformation.2, 3 Patients known to have cysts with a high risk for malignant transformation will optimally be managed surgically. Those with lower-risk cysts may be followed with more or less intensive surveillance programs depending on risk stratification. Avoidance of unnecessary, highly morbid surgery balanced with prevention of pancreatic cancer hinges on accurate preoperative diagnosis and malignant risk stratification.

Diagnostic tools for pancreatic cysts are limited by variable accuracy and reliability. Although cross-sectional imaging can detect the vast majority of pancreatic cysts, its accuracy in differentiating cyst types is lacking.4 Differentiation of cyst types is key because this, in part, will determine their malignant potential. Mucinous pancreatic cystic lesions include intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN), both of which can undergo malignant progression.5 Conversely, nonmucinous cysts include serous cystic neoplasms (SCN) and pseudocysts with virtually no propensity for malignancy and cystic pancreatic neuroendocrine tumors (NET) and solid pseudopapillary neoplasms (SPN), which are rare and almost always identified accurately on cytology. To aid in risk stratification, endoscopic ultrasound with fine needle aspiration is often performed in order to obtain cyst fluid for biomarker, cytologic, and genetic analysis.5 Cyst fluid carcinoembryonic antigen (CEA) is the standard biomarker currently used to differentiate mucinous from nonmucinous pancreatic cysts.6 However, CEA is not perfect. A recent multi-institutional retrospective study found CEA sensitivity and specificity of only 61% and 77%, respectively, at the accepted 192 ng/mL threshold for detection of mucinous cystic lesions.7 Previous meta-analysis reported similar findings of 63% and 88% sensitivity and specificity of CEA.8 Furthermore, CEA measurement requires specific laboratory capabilities that are costly and relatively time consuming.

We hypothesize that an alternative cyst fluid biomarker may offer improved diagnostic accuracy and efficiency over the standard CEA test for determination of mucinous versus nonmucinous cysts. Two previous studies from a single institution reported the potential of pancreatic cyst fluid glucose for the diagnosis of mucinous cysts.9, 10 The studies included 45 and 65 patient samples and found sensitivities and specificities ranging from 81% to 95% and 57% to 78% for detection of mucinous pancreatic cysts using thresholds of <66 and 50 mg/dL, respectively. We aim to independently validate these findings with a larger patient cohort and to compare the diagnostic utility of cyst fluid glucose and CEA.

Section snippets

Methods

Pancreatic cyst fluid samples were collected prospectively at the time of endoscopic ultrasound-guided fine needle aspiration (n = 41) or pancreatic resection (n = 112) at Indiana University Health University Hospital between June 2003 and June 2016. All patients provided informed consent in accordance with the Indiana University institutional review board. After procurement, pancreatic cyst fluid aliquots were placed immediately on ice and then stored at −80° C. Pancreatic cyst diagnosis was

Results

A total of 153 pancreatic cyst fluid samples were collected and analyzed for study inclusion. Of these, 106 were pathologically confirmed as mucinous (25 MCNs, 77 IPMNs, 4 ductal adenocarcinomas) and 47 as nonmucinous cysts (21 SCNs, 9 cystic neuroendocrine tumors, 14 pseudocysts, and 3 solid pseudopapillary neoplasms). Although patient sex did not differ between those with mucinous and nonmucinous cysts (31.7% vs 27.7% male; P = .7), median age (interquartile range, IQR) was significantly

Discussion

International consensus guidelines for the management of mucinous pancreatic cysts (IPMN and MCN) were published in 2006 and updated in 2012 to aid clinicians in the practice of evidence-based cyst management.5, 12 Diagnostic recommendations encourage initial use of clinical and imaging characteristics, specifically computed tomography and magnetic resonance cholangiopancreatography, which may identify classic findings of a particular type of cyst (e.g. IPMN: main duct dilation, main pancreatic

Conclusions

Pancreatic cyst fluid glucose differentiates mucinous from nonmucinous cysts with similar accuracy to the current “gold-standard” CEA. However, glucose testing has several distinct advantages in that it is simple, rapid, and inexpensive and requires minimal cyst fluid. Thus, cyst fluid glucose should routinely be tested to aid in the diagnosis of mucinous pancreatic cysts. Combining CEA and glucose improves diagnostic accuracy and may further approach perfection if evaluated together with

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    Presented at the Central Surgical Association, Chicago, IL, July 2017.

    Financial Disclosures: No authors have financial disclosures or conflicts of interest to report.

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