Differentiation Of Pancreatic Cystic Lesions Research Articles

Diagnostics and Management of Pancreatic Cystic Lesions-New Techniques and Guidelines.

Pancreatic cystic lesions (PCLs) are increasingly diagnosed owing to the wide use of cross-sectional imaging techniques. Accurate identification of PCL categories is critical for determining the indications for surgical intervention or surveillance. The classification and management of PCLs rely on a comprehensive and interdisciplinary evaluation, integrating clinical data, imaging findings, and cyst fluid markers. EUS (endoscopic ultrasound) has become the widely used diagnostic tool for the differentiation of pancreatic cystic lesions, offering detailed evaluation of even small pancreatic lesions with high sensitivity and specificity. Additionally, endoscopic ultrasound-fine-needle aspiration enhances diagnostic capabilities through cytological analysis and the assessment of fluid viscosity, tumor glycoprotein concentration, amylase levels, and molecular scrutiny. These detailed insights play a pivotal role in improving the clinical prognosis and management of pancreatic neoplasms. This review will focus mainly on the latest recommendations for the differentiation, management, and treatment of pancreatic cystic lesions, highlighting their clinical significance.

Quantitative Software Analysis of Endoscopic Ultrasound Images of Pancreatic Cystic Lesions.

Endoscopic ultrasonography (EUS) is the most accurate imaging modality for the evaluation of different types of pancreatic cystic lesions. Our aim was to analyze EUS images of pancreatic cystic lesions using an image processing software. We specified the echogenicity of the lesions by measuring the gray value of pixels inside the selected areas. The images were divided into groups (serous cystic neoplasm /SCN/, intraductal papillary mucinous neoplasms and mucinous cystic neoplasms /Non-SCN/ and Pseudocyst) according to the pathology results of the lesions. Overall, 170 images were processed by the software: 81 in Non-SCN, 30 in SCN and 59 in Pseudocyst group. The mean gray value of the entire lesion in the Non-SCN group was significantly higher than in the SCN group (27.8 vs. 18.8; p < 0.0005). The area ratio in the SCN, Non-SCN and Pseudocyst groups was 57%, 39% and 61%, respectively; significantly lower in the Non-SCN group than in the SCN or Pseudocyst groups (p < 0.0005 and p < 0.0005, respectively). The lesion density was also significantly higher in the Non-SCN group compared to the SCN or Pseudocyst groups (4186.6/mm2 vs. 2833.8/mm2 vs. 2981.6/mm2; p < 0.0005 and p < 0.0005, respectively). The EUS image analysis process may have the potential to be a diagnostic tool for the evaluation and differentiation of pancreatic cystic lesions.

A deep learning algorithm to improve readers' interpretation and speed of pancreatic cystic lesions on dual-phase enhanced CT.

To develop a deep learning model (DLM) to improve readers' interpretation and speed in the differentiation of pancreatic cystic lesions (PCLs) on dual-phase enhanced CT, and a low contrast mediadose, external testing set validated the model. Dual-phase enhanced CT images of 363 patients with 368 PCLs obtained from two centers were retrospectively assessed. Based on the examination date, a training and validation set of 266 PCLs, an internal testing set of 52 PCLswere designated from center 1. Anexternal testing set included 50 PCLs from center 2. Clinical and radiological characteristics were compared. The DLM was developed using 3D specially designed densely connected convolutional networks for PCL differentiation. Radiomic features were extracted to build a traditional radiomics model (RM). Performance of the DLM, traditional RM, and three readers was compared. The accuracy for differential diagnosis was 0.904 with DLM, which was the highest in the internal testing set. Accuracy differences between the DLM and senior radiologist were not significant both in the internal and external testing set (both p > 0.05). With the help of the DLM, the accuracy and specificity of the junior radiologist were significantly improved (all p < 0.05), and all readers' diagnostic time was shortened (all p < 0.05). The DLM achieved senior radiologist-level performance in differentiating benign and malignant PCLs which could improve the junior radiologist's interpretation and speed of PCLs on CT.

Confocal Laser Endomicroscopy Interpretation and Differentiation of Pancreatic Cysts: A Randomized Trial of Teaching Modalities

ABSTRACT Background EUS-guided needle-based confocal laser endomicroscopy (nCLE) has not been widely adopted for the differentiation of pancreatic cystic lesions (PCLs), perhaps due to a perceived difficulty in learning novel CLE image patterns. Hence, we sought to investigate the optimal teaching modality for interpretation of nCLE imaging from PCLs. Methods Sixteen nCLE-naive observers blinded to clinical data were randomized into didactic (classroom-based) versus self-directed (computer-based) teaching groups to review nCLE videos and differentiate mucinous and non-mucinous PCLs. The study was conducted concurrently for both groups in 3 phases. Phase-1-Teaching: both groups received an overview of EUS-nCLE of PCLs. Phase-2-Training: assessment of 20 EUS-nCLE subject-videos; the didactic group had a feedback session with an nCLE expert while the self-directed group received this information via pre-recorded presentation. Phase-3-Testing: assessment of 50 EUS-nCLE subject-videos. Results For all observers (n = 16), the diagnostic accuracy for nCLE-based differentiation of mucinous from non-mucinous PCLs was higher (p=0.005) in the Phase-3-Testing (94.6%, 95%CI: 92-96%) than in Phase-2-Training (89.9%, 95%CI: 85-93%). During Phase-3-Testing, both the didactic and self-directed teaching groups achieved a comparable (p=0.48) diagnostic accuracy of 93.9% and 95.4%, respectively. The interobserver agreement (kappa, standard error) for the differentiation of mucinous from non-mucinous PCLs improved from Phase-2-Training to Phase-3-Testing stage, and was “substantial” for both the didactic (k=0.81, 0.03) and self-directed (k=0.79, 0.03) training groups. Conclusion Notwithstanding didactic and self-directed teaching, a ‘training’ and ‘test’ strategy accomplished high diagnostic accuracies and considerable interobserver agreement among naive observers for EUS-nCLE image differentiation of PCLs; Clinical trial NCT02516488 ( https://clinicaltrials.gov/ct2/show/NCT02516488 )

Radiomics for the Diagnosis and Differentiation of Pancreatic Cystic Lesions.

Radiomics, also known as quantitative imaging or texture analysis, involves extracting a large number of features traditionally unmeasured in conventional radiological cross-sectional images and converting them into mathematical models. This review describes this approach and its use in the evaluation of pancreatic cystic lesions (PCLs). This discipline has the potential of more accurately assessing, classifying, risk stratifying, and guiding the management of PCLs. Existing studies have provided important insight into the role of radiomics in managing PCLs. Although these studies are limited by the use of retrospective design, single center data, and small sample sizes, radiomic features in combination with clinical data appear to be superior to the current standard of care in differentiating cyst type and in identifying mucinous PCLs with high-grade dysplasia. Combining radiomic features with other novel endoscopic diagnostics, including cyst fluid molecular analysis and confocal endomicroscopy, can potentially optimize the predictive accuracy of these models. There is a need for multicenter prospective studies to elucidate the role of radiomics in the management of PCLs.

Endoscopic Ultrasound-Guided Confocal Laser Endomicroscopy Increases Accuracy of Differentiation of Pancreatic Cystic Lesions

Imaging patterns from endoscopic ultrasound (EUS)-guided needle-based confocal laser endomicroscopy (nCLE) have been associated with specific pancreatic cystic lesions (PCLs). We compared the accuracy of EUS with nCLE in differentiating mucinous from nonmucinous PCLs with that of measurement of carcinoembryonic antigen (CEA) and cytology analysis. We performed a prospective study of 144 consecutive patients with a suspected PCL (≥20 mm) who underwent EUS with fine-needle aspiration of pancreatic cysts from June 2015 through December 2018 at a single center; 65 patients underwent surgical resection. Surgical samples were analyzed by histology (reference standard). During EUS, the needle with the miniprobe was placed in the cyst, which was analyzed by nCLE. Fluid was aspirated and analyzed for level of CEA and by cytology. We compared the accuracy of nCLE in differentiating mucinous from nonmucinous lesions with that of measurement of CEA and cytology analysis. The mean size of dominant cysts was 36.4 ± 15.7 mm and the mean duration of nCLE imaging was 7.3 ± 2.8 min. Among the 65 subjects with surgically resected cysts analyzed histologically, 86.1% had at least 1 worrisome feature based on the 2012 Fukuoka criteria. Measurement of CEA and cytology analysis identified mucinous PCLs with 74% sensitivity, 61% specificity, and 71% accuracy. EUS with nCLE identified mucinous PCLs with 98% sensitivity, 94% specificity, and 97% accuracy. nCLE was more accurate in classifying mucinous vs nonmucinous cysts than the standard method (P < .001). The overall incidence of postprocedure acute pancreatitis was 3.5% (5 of 144); all episodes were mild, based on the revised Atlanta criteria. In a prospective study, we found that analysis of cysts by nCLE identified mucinous cysts with greater accuracy than measurement of CEA and cytology analysis. EUS with nCLE can be used to differentiate mucinous from nonmucinous PCLs. ClincialTrials.gov no: NCT02516488.

Pancreatic Cyst Fluid Vascular Endothelial Growth Factor A and Carcinoembryonic Antigen: A Highly Accurate Test for the Diagnosis of Serous Cystic Neoplasm

Accurate differentiation of pancreatic cystic lesions is important for pancreatic cancer early detection and prevention as well as avoidance of unnecessary surgical intervention. Serous cystic neoplasms (SCN) have no malignant potential, but may mimic premalignant mucinous cystic lesions: mucinous cystic neoplasm (MCN) and intraductal papillary mucinous neoplasm (IPMN). We recently identified vascular endothelial growth factor (VEGF)-A as a novel pancreatic fluid biomarker for SCN. We hypothesize that combining cyst fluid carcinoembryonic antigen (CEA) with VEGF-A will improve the diagnostic accuracy of VEGF-A. Pancreatic cyst/duct fluid was collected from consenting patients undergoing surgical cyst resection with corresponding pathologic diagnoses. Pancreatic fluid VEGF-A and CEA levels were detected by ELISA. One hundred forty-nine patients with pancreatic cystic lesions met inclusion criteria. Pathologic diagnoses included pseudocyst (n=14), SCN (n=26), MCN (n=40), low/moderate grade IPMN (n=34), high grade IPMN (n=20), invasive IPMN (n=10) and solid pseudopapillary neoplasm (n=5). VEGF-A was significantly elevated in SCN cyst fluid compared to all other diagnoses (p<0.001). With a threshold of >5,000 pg/ml, VEGF-A alone has 100% sensitivity and 83.7% specificity to distinguish SCN from other cystic lesions. With a threshold of ≤10ng/ml, CEA alone identifies SCN with 95.5% sensitivity and 81.5% specificity. Sensitivity and specificity of the VEGF-A/CEA combination are 95.5% and 100% respectively. The c-statistic increased from 0.98 to 0.99 when CEA was added to VEGF-A alone in the ROC analysis. Although VEGF-A alone is a highly accurate test for SCN, the combination of VEGF-A with CEA approaches the gold-standard of pathologic diagnosis, thus importantly avoiding false positives. Patients with a positive test indicating benign SCN can be spared a high risk surgical pancreatic resection.

Validation of diagnostic characteristics of needle based confocal laser endomicroscopy in differentiation of pancreatic cystic lesions.

Background and aims: Endoscopic ultrasound (EUS)-guided needle-based Confocal Laser Endomicroscopy (nCLE) characteristics of pancreatic cystic lesions (PCLs) have been identified in studies where the gold standard surgical histopathology was available in a minority of patients. There are diverging reports of interobserver agreement (IOA) and paucity of intraobserver reliability (IOR). Thus, we sought to validate current EUS-nCLE criteria of PCLs in a larger consecutive series of surgical patients. Methods: A retrospective analysis of patients who underwent EUS-nCLE at a single center was performed. For calculation of IOA (Fleiss’ kappa) and IOR (Cohen’s kappa), blinded nCLE-naïve observers (n = 6) reviewed nCLE videos of PCLs in two phases separated by a 2-week washout period. Results: EUS-nCLE was performed in 49 subjects, and a definitive diagnosis was available in 26 patients. The overall sensitivity, specificity, and accuracy for diagnosing a mucinous PCL were 94 %, 82 %, and 89 %, respectively. The IOA for differentiating mucinous vs. non-mucinous PCL was “substantial” (κ = 0.67, 95 %CI 0.57, 0.77). The mean (± standard deviation) IOR was “substantial” (κ = 0.78 ± 0.13) for diagnosing mucinous PCLs. Both the IOAs and mean IORs were “substantial” for detection of known nCLE image patterns of papillae/epithelial bands of mucinous PCLs (IOA κ = 0.63; IOR κ = 0.76 ± 0.11), bright particles on a dark background of pseudocysts (IOA κ = 0.71; IOR κ = 0.78 ± 0.12), and fern-pattern or superficial vascular network of serous cystadenomas (IOA κ = 0.62; IOR κ = 0.68 ± 0.20). Three (6.1 % of 49) patients developed post-fine needle aspiration (FNA) pancreatitis. Conclusion: Characteristic EUS-nCLE patterns can be consistently identified and improve the diagnostic accuracy of PCLs. These results support further investigations to optimize EUS-nCLE while minimizing adverse events.Study registration: NCT02516488

Pancreatic cystic lesions: classification, diagnosis and treatment

Pancreatic cystic lesions (PCLs) are being increasingly identified in recent years. The diagnosis and discrimination of these lesions are very important because of the risk for concurrent or later development of malignancy. Pcls are usually first diagnosed in adults and characterized by conventional imaging modalities such as trans-abdominal ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI). However, their ability to differentiate the benign and malignant lesions remains limited. Endoscopic US may be more helpful for the diagnosis and differentiation of PCLs because of its high resolution and better imaging characteristics than cross-sectional imaging modalities. It also allows for fine-needle aspiration (FNA) of cystic lesions is biochemical, cytological and DNA analysis that might be further helpful for diagnosis and differentiation. Owing to improvements in imaging techniques, cystic lesions of the pancreas are being identified more often, even in patients who are asymptomatic. These range from benign to premalignant lesions to highly malignant. Due to the high morbidity related to pancreatic resections, the surgeon should balance very carefully the advantages of the radical resection with the risks of an unrequested dangerous procedure. This review offers guidance on the strategies for establishing the diagnosis, assessing risk, and making difficult decisions about when surgical resection is indicated. While many CNPs have an indolent behaviour that justifies surveillance, others should be resected because of the risk of progression to invasive cancer.

Cystic lesions of the pancreas: more reliable differentiation with in situ high-resolution optical imaging?

Pancreatic cystic lesions (PCLs) represent an increasingly common diagnostic and therapeutic challenge. A significant number of pancreatic cysts are detected incidentally when noninvasive abdominal imaging is performed for an unrelated diagnosis [1]. The vast majority of PCLs are cystic neoplasms (~60%), while injury or inflammation-related cysts (e.g., pseudo cysts) account for approximately 30% of PCLs. The remaining PCLs are congenital or miscellaneous cysts [2]. Neoplastic cysts include intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs), serous cystic neoplasms (SCNs), solid pseudopapillary neoplasms (SPNs), cystic endocrine neoplasms, ductal adenocarcinomas with cystic degeneration and acinar-cell cystic neoplasms [3]. Since the management of PCLs is a function of cyst type, reliable differentiation between the five most common diagnoses – pseudocyst, IPMN, MCN, SCN and SPN – is of vital importance [4]. Differentiation of PCLs Although a number of characteristic imaging features have been reported, many PCLs, especially those with diameter <2 cm, are extremely difficult to differ entiate by imaging [5]. Differentiation of low-risk lesions and high-risk lesions is also difficult. Low-risk lesions (pseudo cysts, SCNs, congenital cysts and lympho epithelial cysts) are generally not resected because they have no risk or an extremely low risk of malignant transformation [2]. High-risk lesions are mucin-producing tumors (MCNs and IPMNs) and some cystic variants of solid tumors (e.g., ductal adenocarcinomas with cystic degeneration) [2,4]. Depending on the degree of dysplasia, MCNs and IPMNs are classified as MCN/IPMN with low- or intermediategrade dysplasia, MCN/IPMN with highgrade dysplasia and MCN/IPMN with an associated invasive carcinoma [6].

Acoustic radiation force impulse (ARFI) ultrasound imaging of pancreatic cystic lesions

Purpose To evaluate the ARFI ultrasound imaging with Virtual Touch tissue quantification in studying pancreatic cystic lesions, compared with phantom fluid models. Materials and methods Different phantom fluids at different viscosity or density (water, iodinate contrast agent, and oil) were evaluated by two independent operators. From September to December 2008, 23 pancreatic cystic lesions were prospectively studied. All lesions were pathologically confirmed. Results Non-numerical values on water and numerical values on other phantoms were obtained. Inter-observer evaluation revealed a perfect correlation ( rs = 1.00; p < 0.0001) between all measurements achieved by both operators per each balloon and fluid. Among the pancreatic cystic lesions, 14 mucinous cystadenomas, 4 pseudocysts, 3 intraductal papillary-mucinous neoplasms and 2 serous cystadenomas were studied. The values obtained ranged from XXXX/0–4,85 m/s in mucinous cystadenomas, from XXXX/0–3,11 m/s in pseudocysts, from XXXX/0–4,57 m/s in intraductal papillary-mucinous neoplasms. In serous cystadenomas all values measured were XXXX/0 m/s. Diagnostic accuracy in benign and non-benign differentiation of pancreatic cystic lesions was 78%. Conclusions Virtual Touch tissue quantification can be applied in the analysis of fluids and is potentially able to differentiate more complex (mucinous) from simple (serous) content in studying pancreatic cystic lesions.

CEAtTo Amylase Ratio for the Diagnosis of Malignant and Premalignant Cystic Lesions of the Pancreas

Introduction: The differentiation of pancreatic cystic lesions between those with significant malignant potential (mucinous cystadenomas, cystadenocarcinomas) from cysts without this potential (serous cystadenomas, pseudocysts) is challenging. EUS-FNA cytology may be non-diagnostic and tumor markers have imperfect sensitivity and specificity. Both cyst fluid CEA and amylase have been advocated as useful markers. Aim: To determine if the ratio of CEA to amylase improves diagnostic accuracy over either marker alone. Methods: A retrospective chart review was performed of all cases of pancreatic cysts evaluated by EUS-FNA from October 2001 to September 2004. The final histology of the cysts was determined by surgical pathology or clinical follow-up with radiographic imaging. Those in whom CEA (ng/ml) and amylase (U/L) levels were measured were included in the study. EUS-FNA was done using the Pentax FG-36UX echoendoscope and Wilson-Cook 22 gauge needle. Sensitivity and specificity were calculated for each marker and also for the ratio CEA/ln(Amylase). Cut off values were determined by ROC analysis. Results: 25 patients (12M, 13F) had EUS-FNA of pancreatic cysts and final histology determined by surgery and clinical follow-up. 18 patients had both CEA and amylase levels and formed the study cohort. There were 9 males and 9 females, mean age 57yrs (range 28-83). Five had neoplastic cysts (1 cancer, 4 mucinous) determined by surgical pathology, and 13 had benign cysts (11 pseudocysts, 2 serous). 6 of the 13 benign cysts were confirmed surgically and 7 showed resolution on repeat imaging at 6-24 months consistent with benign pseudocysts. See Table. Conclusions: CEA>150 ng/ml was the single best predictor for malignant and premalignant cystic pancreatic lesions. The CEA/ln(Amylase) ratio > 40 may improve specificity without loss of sensitivity.

Accuracy of Endoscopic Ultrasound, Fine Needle Aspiration, Cytology, and Cyst Fluid Tumor Markers in Patients with Pancreatic Cystic Lesions: Comparison with Surgical Pathology and 12-month Follow-up

Background: Preoperative differentiation of pancreatic cystic lesions (PCL) remains difficult despite improvement in imaging modalities and cystic fluid analysis. The aim of this study was to assess the diagnostic accuracy of endoscopic ultrasonography (EUS) and fine needle aspiration (FNA) with tumor marker measurement in the diagnosis of PCLs. Methods: The records of 56 consecutive patients with PCLs referred to a gastroenterologist and pancreatic surgeon were reviewed. The mean age was 60.4 yrs and 66% were female. Eighteen percent had a history of pancreatitis and 59% had symptoms of abdominal pain. The mean cyst size was 20mm; 7% were <1cm and 21% were >5cm. Cyst location was the head or uncinate in 38%. EUS was performed in 30 (54%). FNA was performed in 46 (82%) of them. The results of EUS, cytology, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) levels were compared with the final diagnosis. Based on surgical pathology and/or an imaging follow-up of at least 12 mos, cysts were classified as benign (simple cysts, pseudocyst, serous cystadenoma) or malignant/potentially malignant (mucinous cystadenoma, solid-pseudopapillary tumors, cystic adenocarcinomas). Receiver-operator curve (ROC) analysis was used to determine ideal cutoffs for the cyst tumor markers. Results: Final diagnosis was obtained in 41 (89%) of 46 cases; 23 (50%) had surgery. Sensitivity, specificity and positive and negative predictive value of EUS (without FNA) to distinguish benign from malignant/premalignant PCL were 50%, 56%, 36% and 69% and for cytology were 71%, 96%, 92% and 82%, respectively. CA 19-9 >37 U/ml had a 70% sensitivity and 90% specificity, whereas CEA >3.1 ng/ml had a 70% sensitivity and 85% specificity. High levels of CEA (>100ng/ml were never seen in benign lesions: 100% specific). Areas under the curve for cytology and tumor markers were similar (0.78-0.83). Conclusion: Tumor marker analysis of fluid retrievable by EUS with FNA was found to be a very useful tool in distinguishing benign from malignant/premalignant PCL and similar in performance to cytology.

EUS in the evaluation of pancreatic cystic lesions

Background: The differential diagnosis in pancreatic cystic lesions is often difficult despite the availability of various modern imaging modalities. This study assessed the role of EUS in the following: (1) discrimination of pseudocysts from pancreatic cystic tumors, (2) differential diagnosis between serous cystadenoma and mucinous cystic tumor, and (3) prediction of accompanying malignancy in intraductal papillary mucinous tumor. Methods: EUS findings in 75 patients with pancreatic cystic lesions (58 cystic tumors, 17 pseudocysts) were evaluated. In the comparison of pseudocysts and cystic tumors, the latter included intraductal papillary mucinous tumor, mucinous cystic tumors, and serous cystadenomas, but not solid-pseudopapillary tumors. Results: In univariate analysis, pseudocysts exhibited echogenic debris and parenchymal changes more often than cystic tumors did (respectively, 29% vs. 6%, p < 0.05; and 65% vs. 4%, p < 0.001). In contrast, septa and mural nodules were found more frequently in cystic tumors than pseudocysts (respectively, 69% vs. 12%, p < 0.001; 56% vs. 12%, p < 0.01). Multivariate analysis revealed that parenchymal changes (odds ratio [OR] = 83.59; p < 0.01); septa (OR = 30.75; p < 0.05); and mural nodules (OR = 21.38; p < 0.05) were independent predictors of differentiation between pseudocysts and cystic tumors. Serous cystadenoma exhibited diverse EUS features, as well as a honeycomb appearance. Mural nodules were found more often in mucinous cystic tumors than in serous cystadenomas ( p < 0.05). There were no factors that predicted malignancy in intraductal papillary mucinous tumor. Conclusions: EUS is a useful complementary imaging method for differentiation of pancreatic cystic lesions. (Gastrointest Endosc 2003;57:891-6.)

The Endocrine and Pancreatic Unit at the University of Verona, Italy

The Endocrine and Pancreatic Unit at the University of Verona, Italy