Study design
We performed a case control retrospective study, using the databases of Galilee Medical Center. All patients above 18 years old who were referred to EUS and who had EUS morphological diagnosis of pancreatic cysts from 1.4.2011 till 1.10.2019 were included in the study. Patients were excluded if they had hepato-biliary malignancy, obstructive jaundice, chronic pancreatitis, and abnormal liver function tests. Extracted data included demographic variables (age, gender), smoking, personal or family history of malignancy, EUS findings, presence of gallbladder, CBD stones, CBD width by EUS and the morphological diagnosis. All procedures were carried out via linear echoendoscope (Pentax-Japan), model 3870 and performed by a single gastroenterologist with more than 10 years’ experience in the field of Endoscopic Ultrasound. Patients were placed in the left lateral decubitus position and were sedated with intravenous midazolam and propofol according to the decision of the endoscopist. All methods were performed in accordance with the relevant guidelines and regulations
Diagnosis Of Pancreatic Cystic Lesions
The diagnosis of pancreatic cystic lesions in our study was based on two criteria, the morphological EUS criteria and the biochemical cyst analysis (amylase and Carcinoembryonic antigen (CEA)), as follows:
Morphologic Sonographic Characterization Of Pancreatic Cyst
Four types of pancreatic cysts were reported in our study. The morphologic sonographic diagnosis of the pancreatic cysts in our study was made according to the following characteristics: 1) IPMNs: MD-IPMNs defined by pancreatic duct dilatation in EUS without obstructing lesion or stone while branch duct type is characterized by cystic dilation of branch ducts connected to the main pancreatic duct, whereas, mixed type represents a combination of both types [15]. 2) Mucinous cystic neoplasm (MCN) defined by multiple locules, or unilocular, most commonly located in the body or tail of pancreas and [15] [16]. 3) Serous cyst adenoma (SCA) defined by focal lesion that may be located anywhere in the pancreas resembling a honeycomb with pathognomonic central calcification in up to 20% of cases [17], and 4) Pseudocyst (PC) defined by extra pancreatic cyst with thin muddy-brown debris after an episode of moderate to severe pancreatitis [18].
Biochemical Cyst Fluid Analysis
The cyst fluid was analyzed for amylase and CEA level. Unfortunately, reported sensitivities and specificities of chemical analyses have broad ranges, making interpretation difficult [19] [20]. The American society of gastrointestinal endoscopy (ASGE) guidelines recommend a cut-off level of CEA of > 192 ng/mL for pancreatic mucinous cysts (MCA and IPMN) and CEA < 5 ng\mL for serous cysts. [18] However, it doesn’t recommend a cut-off level for cyst amylase. Similarly, the World Gastroenterology Guidelines, report a CEA level > 192 ng\mL for mucinous cysts: IPMN and MCN (sensitivity 73%, specificity 84%) and < 5 ng\mL for serous cysts (sensitivity 100% and specificity 86%) (WGO Global Guideline Pancreatic Cystic Lesions 2019). For PC, The European Study Group on Cystic Tumors of the Pancreas guidelines reported that low level amylase may exclude pancreatic pseudocysts (amylase < 250 U/L; sensitivity 44%, specificity 98%) [21]. Therefore, in our study, the agreement between the morphologic sonographic diagnosis and the FNA cyst fluid analysis results were set as CEA > 192 ng\Ml for mucinous cysts while CEA < 5 ng\mL for diagnosis of SCA and amylase > 250 unit\lit for PC.
Statistical analysis
Univariate descriptive statistic was used to compare patients with IPMN diagnosis and other pancreatic cystic lesions. Data was reported as mean ± standard deviation for quantitative continuous variables, and frequencies (percentages) for categorical variables. Univariate regression was used to estimate odds ratio (OR) of baseline factors and multiple linear regression analysis was used to eliminate the effect of confounders. A threshold for statistical significance was set at a P value < 0.05. All analyses were performed by an experienced statistician using the statistical analysis software (SAS Vs 9.4 Copyright (c) 2016 by SAS Institute Inc., Cary, NC, USA).