Characterization Of Pancreatic Lesions Research Articles

Comparison between triphasic CT and EUS pancreatic biopsy in characterization of pancreatic lesions

Comparison between triphasic CT and EUS pancreatic biopsy in characterization of pancreatic lesions

4D Free-Breathing Sequence For The Study Of Pancreatic Lesions In MRI 3 Tesla

Pancreatic cancer is the fourth leading cause of cancer death in both the United States and Europe. A fundamental role in the characterization, early diagnosis, and staging of pancreatic cancer is played by Magnetic Resonance. An innovative and recently implemented sequence, the 4D Free-Breathing sequence, is demonstrating remarkable efficiency in the characterization of pancreatic lesions, as it allows to obtain images with high temporal resolution on the arterial phase, maintaining high spatial and temporal resolution, with the patient free breathing and with compensation of respiratory movement artifacts. The aim of this study was to analyze the 4D Free-Breathing sequence technique and to evaluate its advantages in terms of image quality and diagnostic value in the characterization of pancreatic lesions. The 4D Free Breathing sequence replaces the acquisition of the classic arterial post-contrast phase obtained with the 3D-THRIVE sequence: after a first acquisition of the k-space data in the non-contrast phase (lasting 58 seconds), multiple arterial subphases, each one lasting about 5 seconds, will be acquired with a complete coverage of the post-contrast phase of about 90 seconds. This sequence exploits the k-space sampling technique called "Stack of Stars", based on a radial sampling in the XY plane. In detail, along the slice phase-encoding direction (kz), uniform Cartesian-grid sampling is maintained. Within each kz-encoded plane, radial data is collected with consecutive views (1 per sequence repetition time TR) rotated by a golden-angle of 111.25°, allowing the sampling of a complete circle, also determining a considerably reduced presence of breath artifacts.

4D Free-Breathing Sequence For The Study Of Pancreatic Lesions In MRI 3 Tesla

Pancreatic cancer is the fourth leading cause of cancer death in both the United States and Europe. A fundamental rolein the characterization, early diagnosis, and staging of pancreatic cancer is played by Magnetic Resonance. An innovative and recently implemented sequence, the 4D Free-Breathing sequence, is demonstrating remarkable efficiencyin the characterization of pancreatic lesions, as it allows to obtain images with high temporal resolution on the arterial phase, maintaining high spatial and temporal resolution, with the patient free breathing and with compensationof respiratory movement artifacts. The aim of this study was to analyze the 4D Free-Breathing sequence techniqueand to evaluate its advantages in terms of image quality and diagnostic value in the characterization of pancreaticlesions. The 4D Free Breathing sequence replaces the acquisition of the classic arterial post-contrast phase obtainedwith the 3D-THRIVE sequence: after a first acquisition of the k-space data in the non-contrast phase (lasting 58seconds), multiple arterial subphases, each one lasting about 5 seconds, will be acquired with a complete coverageof the post-contrast phase of about 90 seconds. This sequence exploits the k-space sampling technique called “Stackof Stars”, based on a radial sampling in the XY plane. In detail, along the slice phase-encoding direction (kz), uniform Cartesian-grid sampling is maintained. Within each kz-encoded plane, radial data is collected with consecutiveviews (1 per sequence repetition time TR) rotated by a golden-angle of 111.25°, allowing the sampling of a completecircle, also determining a considerably reduced presence of breath artifacts. The inclusion of the 4D Free-Breathingsequence in the MRI study protocol of the pancreas, through the rapid and consequential acquisitions of 18 arterialphases, allows to improve the diagnostic information contained in the arterial phase, with free breathing, also innon-compliant patients and with correction of breath artifacts

Restricted Water Diffusion in Diffusion-Weighted Magnetic Resonance Imaging in Pancreatic Cancer is Associated with Tumor Hypoxia.

Simple SummaryPancreatic cancer is characterized by a dense network of connective tissue surrounding clusters of cancer cells, the so-called stroma. This ubiquitous connective tissue impairs the delivery of oxygen to cancer cells. This results in hypoxia, which renders the cancer more aggressive and more resistant to treatment. In the present study, we investigated whether the extent of hypoxia in pancreatic cancer can be predicted by magnetic resonance imaging (MRI), a widely used medical imaging technique. More specifically, we used an MRI sequence which can quantitate the random motion (i.e., diffusion) of water molecules within the cancer tissue, namely diffusion-weighted (DW) MRI. We found that the random motion of water molecules is lower in cancer lesions with high hypoxia compared to those with low hypoxia. The findings from our study imply that DW-MRI can be used to identify pancreatic cancer lesions with high hypoxia which are at high risk for treatment failure.Hypoxia is a hallmark of pancreatic cancer (PDAC) due to its compact and extensive fibrotic tumor stroma. Hypoxia contributes to high lethality of this disease, by inducing a more malignant phenotype and resistance to radiation and chemotherapy. Thus, non-invasive methods to quantify hypoxia could be helpful for treatment decisions, for monitoring, especially in non-resectable tumors, or to optimize personalized therapy. In the present study, we investigated whether tumor hypoxia in PDAC is reflected by diffusion-weighted magnetic resonance imaging (DW-MRI), a functional imaging technique, frequently used in clinical practice for identification and characterization of pancreatic lesions. DW-MRI assesses the tissue microarchitecture by measuring the diffusion of water molecules, which is more restricted in highly compact tissues. As reliable surrogate markers for hypoxia, we determined Blimp-1 (B-lymphocyte induced maturation protein), a transcription factor, as well as vascular endothelial growth factor (VEGF), which are up-regulated in response to hypoxia. In 42 PDAC patients, we observed a close association between restricted water diffusion in DW-MRI and tumor hypoxia in matched samples, as expressed by high levels of Blimp-1 and VEGF in tissue samples of the respective patients. In summary, our data show that DW-MRI is well suited for the evaluation of tumor hypoxia in PDAC and could potentially be used for the identification of lesions with a high hypoxic fraction, which are at high risk for failure of radiochemotherapy.

Current Status of Endoscopic Ultrasound Techniques for Pancreatic Neoplasms.

Endoscopic ultrasound (EUS) now plays an important role in the management of pancreatic neoplasms. There are various types of pancreatic neoplasms, from benign to malignant lesions, and the role of EUS ranges from the imaging diagnosis to treatment. EUS is useful for the detection, characterization, and tissue acquisition of pancreatic lesions. Recent advancement of contrast-enhanced harmonic EUS and elastography enables better characterization of pancreatic lesions. In addition to these enhanced EUS imaging techniques, EUS-guided tissue acquisition is now the standard procedure to establish the pathological diagnosis of pancreatic neoplasms. While these diagnostic roles of EUS have been established, EUS-guided interventions such as ablation and drainage are also increasingly utilized in the management of pancreatic neoplasms. However, most of these EUS-guided interventions are not yet standardized in terms of techniques and devices and thus need further investigations.

Impact of Preoperative Endoscopic Ultrasound in Patients Undergoing Surgery for Non-cystic Lesions of the Pancreas

Introduction: Endoscopic ultrasound (EUS) is a standard modality in characterization of pancreatic lesions, especially in those patients who may undergo surgical resection. Our aims were to evaluate the impact and accuracy of preoperative EUS in patients who underwent surgical resection of non-cystic lesions of the pancreas. Methods: This was a single center retrospective study. Using CPT codes, patients with pancreatic lesions were identified over a 4 year period. ICD-9 codes were further utilized to determine which patients underwent EUS, surgery or both. Data analyzed included patient's clinical history, imaging and laboratory analysis. Results: The presence of any pancreatic diagnosis was identified in 6096 patients, of which 916 patients had only EUS and no surgical intervention. On the contrary, 174 patients had surgical intervention without preoperative EUS. 297 patients had palliative care consults for advanced malignancy with no further invasive work-up. Finally, 4923 patients had neither EUS nor surgical intervention. 96 patients that had both preoperative EUS followed by surgical resection were identified. Of these 96 patients, final surgical pathological diagnoses revealed 63 non-cystic lesions. Preoperative EUS diagnoses were correlated with final surgical pathology to determine concordance. Patient demographics, time from EUS to surgery, lesion size, number of FNA passes, and Ca19-9 levels were not statistically different between the groups (Table 1). Preoperative endoscopic work-up including EUS was accurate in 48/63 (76%) patients. The accuracy was improved to 53/63 (84%) patients when suspicious or atypical cytology was considered as a positive result. The most common diagnoses were adenocarcinoma 42/63 (67%), neuroendocrine tumors 9/63 (14%), and autoimmune pancreatitis 4/63 (6%). The accuracy for adenocarcinoma was 37/42 (88%) and for neuroendocrine tumors was 6/9 (67%). In the autoimmune group, malignancy was ruled out in 4/4(100%)(Table 2). In 11/63 (17%) patients in whom initial EUS-FNA was nondiagnostic, a repeat EUS-FNA resulted in a positive diagnosis in 7/11 (64%) patients. However in 4/11 (36%) patients repeat EUS-FNA remained nondiagnostic. Finally in 15/63 (24%) patients, preoperative EUS and final surgical pathology was discordant.Table 1: Demographics; EUS and surgical pathologyTable 2: Pathology dataConclusion: Based upon our data, EUS has an acceptable preoperative accuracy for non-cystic lesions in patients undergoing surgical resection. The most commonly identified pathology was adenocarcinoma for which endoscopic accuracy was 88%. Improvements in non-invasive imaging, identification of novel biomarkers, and refinements in EUS imaging, tissue acquisition and analysis are needed for better diagnosis of pancreatic lesions.

Pitfalls in Pancreatic Imaging

Introduction The use of multidetector computed tomography (CT) and magnetic resonance imaging (MRI) with imaging protocols optimized for imaging of the pancreas has improved the localization as well as the detection and the characterization of pancreatic lesions. Although the typical radiological appearances of common pancreatic lesions is well known, there are several potential pitfalls that can be encountered in pancreatic imaging, such as pancreatic anatomical variants mimicking pancreatic lesions, inflammatory conditions mimicking malignancy, atypical radiological appearance of pancreatic adenocarcinoma, and cystic pancreatic lesions and peripancreatic lesions mimicking intrapancreatic lesions. An understanding of these potential pitfalls in pancreatic imaging is essential to avoid misdiagnosis that can result in inappropriate patient management.

Tu1693 Impact of Pre-Operative Endoscopic Ultrasound in Patients Undergoing Surgery for Cystic Lesions of the Pancreas

Endoscopic ultrasound (EUS) is a standard modality in characterization of pancreatic lesions, especially in those patients who may undergo surgical resection. With increased detection of incidental pancreatic cystic lesions on routine cross sectional imaging, EUS is utilized more frequently in the work up of such patients. Furthermore there is an increasing need for reliable indicators to improve EUS accuracy in accurately identifying such lesions. Aims: To evaluate the impact of pre-operative EUS in patients who underwent surgical resection of pancreatic cystic lesions.

Tu1680 MAnagement of Patients With Pancreatic Cysts Using Integrated Molecular Pathology

surgical resection had a diagnosis of malignancy. Conclusion: 1) Patients with pancreas mass lesions who have EUS FNA cytology results suspicious for malignancy have a 90% chance of subsequent malignancy confirmed. 2) Patients with pancreas mass lesions who have atypical EUS FNA cytology results have a 68% chance of subsequent malignancy confirmed. Furthermore, repeat EUS FNA is performed more often in patients with atypical cytology. 4) The percentages of patients who ultimately underwent a surgical operation were similar between the two groups. 5) Further research is needed to know the true risk of malignancy in indeterminate cytology groups. Tu1678 External Retrospective Validation of Needle-Based Confocal LASER Endomicroscopy (nCLE) Criteria for Pancreatic Cysts David L. Carr-Locke, Manoop S. Bhutani, Oleh Haluszka, Frank G. Gress, Kevin E. Woods, Bertrand Napoleon* Beth Israel, New York, NY; MD Anderson, Houston, TX; Temple University, Philadelphia, PA; Columbia University, New York, NY; Emory University, Atlanta, GA; Hopital Prive Jean Mermoz, Lyon, France Introduction: nCLE is an imaging technique, enabling microscopic observation of solid organs, in vivo and in real-time, during an EUS-FNA procedure. This technique could potentially provide useful information to establish a differential diagnosis between mucinous and non-mucinous neoplasms. A recent prospective multicenter French study, CONTACT (Needle-based confocal laser endomicroscopy (nCLE) for the diagnosis of pancreatic cysts: validation of the described criteria, Napoleon et al., UEGW 2014, OP 282), assessed the diagnostic performance of nCLE for the diagnosis of pancreatic cysts. In this study, the nCLE specificity for serous cystadenoma (SCA), mucinous cystic neoplasm (MCN), and pseudocyst were 100%, 95%, and 96% respectively. This US retrospective study aims at externally validating those results through a retrospective evaluation of the nCLE performance and the interobserver agreement for the characterization of pancreatic cysts. Materials and Methods: Five independent gastroenterologists conducted a blinded, individual, retrospective review of 31 nCLE sequences after a short training session on image interpretation delivered by an nCLE expert. Training consisted of a review of current nCLE criteria for each cyst type with corresponding sample sequences. The sequences then reviewed consisted of 13 serous cystadenomas, 6 mucinous cystadenomas, 5 IPMNs, and 7 pseudocysts. Their performance was compared to that of CONTACT reviewers. Results: Performance results are reported in table 1. Performance values obtained correlated with CONTACT results, especially for those sequences evaluated with “high confidence”. Interobserver agreement were kappa Z 0.71, 0.65, and 0.9 for SCA, MCN, and pseudocysts respectively. Conclusions: This study demonstrates that after brief training on nCLE image interpretation criteria for the characterization of pancreatic lesions, a high level of performance can be achieved for the characterization of pancreatic lesions. This suggests that accurate interpretation of nCLE images for pancreatic cysts can be learned rapidly, with a high level of confidence in 72.6% of the cases.

Dual-phase 18F-FDG PET/CT imaging in the characterization of pancreatic lesions: does it offer prognostic information?

The primary aim of our prospective study was to evaluate the usefulness of dual-phase F-fluoro-deoxy-glucose PET/computed tomography (F-FDG PET/CT) in the characterization of pancreatic masses. The secondary aim was to assess whether delayed imaging revealed any prognostic information. Fifty patients with periampullary or pancreatic masses on conventional imaging were included in this study. Early and delayed PET/CT was performed, followed by pathological examination in all patients. PET/CT parameters including uptake pattern, SUVearly, SUVdelayed, lesion to background ratio (L/B), and retention index (RI) were assessed for their ability to differentiate benign from malignant lesions. Patients with malignant lesions were followed up for a median duration of 26 months. The association of 11 variables with survival was analyzed by univariate and multivariate methods. Thirty-one patients had malignant lesions and 19 had benign lesions. The mean SUVearly, L/B, SUVdelayed, and RI between the malignant and benign lesions were statistically significant. The F-FDG uptake pattern of the lesions had higher sensitivity (93.5%) and specificity (100%) compared with RI (cutoff 25.7%) (84 and 37%, respectively) for diagnosing malignancy (P<0.05). In univariate analysis both RI (>18.7%) and tumor size (>2.6 cm) predicted significantly poor survival, whereas in multivariate analysis RI (P=0.04) was the only predictor of poor survival. Dual-phase F-FDG PET/CT is not useful in characterizing pancreatic masses as it cannot differentiate benign from malignant lesions, and focal uptake on early PET imaging is the best indicator of malignancy. A possible benefit in performing a delayed scan is that a high RI (>18.7) can predict poor survival and hence may be useful in treatment planning.

Can miRNA Biomarkers Be Utilized to Improve the Evaluation and Management of Pancreatic Cystic Lesions?

AbstractThis article reviews the current strategies and challenges of diagnosing pancreatic cystic lesions, and presents an overview of molecular tools that are available to enhance diagnostic accuracy. Specifically, we highlight the emergence of microRNAs (miRNAs) as diagnostic markers. miRNA signatures have been reported for both solid tissue and biofluid specimens, including cyst fluid, collected from patients with solid and cystic pancreatic lesions. These miRNA signatures offer the opportunity to improve molecular characterization of pancreatic lesions, to help guide clinical management through early diagnosis and informed prognosis, and to provide novel therapeutic targets for pancreatic cancer.

Diffusion-weighted MR Imaging of Solid and Cystic Lesions of the Pancreas

Diffusion-weighted magnetic resonance (MR) imaging is increasingly used in the detection and characterization of pancreatic lesions. Diffusion-weighted imaging may provide additional information to radiologists evaluating patients who have cystic or solid neoplasms of the pancreas. Because of greater freedom of motion of water molecules in fluid-rich environments, simple cysts in the pancreas have higher signal intensity on diffusion-weighted images with a b value of 0 sec/mm2 and lower signal intensity on high-b-value images. High apparent diffusion coefficient (ADC) values can be obtained on ADC maps because of the T2 “shine-through” effect. In contrast, solid neoplasms of the pancreas show increased signal intensity relative to the pancreas on diffusion-weighted images with a b value of 0 sec/mm2 and relatively high signal intensity on high-b-value images. Diffusion-weighted imaging can help detect solid pancreatic neoplasms with extremely dense cellularity or extracellular fibrosis by demonstrating significantly low ADC values, and these neoplasms may be better detected on diffusion-weighted MR images because of better contrast, although the resolution is generally worse. However, diffusion-weighted imaging may not be capable of helping definitively characterize solid lesions as inflammatory or neoplastic because of an overlap in ADC values between the two types. For example, it is difficult to distinguish poorly differentiated pancreatic adenocarcinoma from mass-forming pancreatitis at diffusion-weighted imaging because of similarly low ADC values attributed to dense fibrosis.

Pancreatic multicenter ultrasound study (PAMUS)

To describe the typical CEUS pattern of pancreatic lesions and to evaluate the diagnostic accuracy of Contrast-enhanced ultrasound (CEUS) in their characterization. All US and CEUS examinations of focal pancreatic masses performed in six centers during a period of five years were reviewed. Inclusion criteria were: focal pancreatic mass pathologically proved, visible at ultrasound (US) and studied with CEUS. All lesions were then evaluated for size, aspect and enhancement pattern. Sensitivity, specificity, positive and negative predictive values with 95% CIs were calculated to define diagnostic accuracy of CEUS in respect to pathology. Diagnostic confidence of US and CEUS, discerning between benign and malignant lesions, were represented by using ROC (receiver operating characteristics) curves. Agreement was evaluated by means of k statistics. 1439 pancreatic lesions were included. At CEUS the lesions were divided into solid (89%) and cystic (12%) masses and classified into six and eight categories, respectively. Among the solid lesions, adenocarcinomas were characterized with an accuracy of 87.8%. Among the cystic lesions, cystic tumors were diagnosed with an accuracy of 97.1%. ROC curve area increased from 0.637 for US to 0.877 for CEUS (p<0.0001). Inter-observer agreement was slightly higher for solid (k=0.78) than cystic (k=0.62) lesions. In none of the centers side effects were reported. CEUS is accurate in the characterization of pancreatic lesions. CEUS should be considered as a complementary imaging method for pancreatic lesions characterization.

1117: Role of Second Generation Contrast-Enhanced Ultrasonography (CEUS) in Diagnosis of Pancreatic Lesions

The development of CEUS has contributed to improve the diagnosis of pancreatic lesions. However, only few controlled studies are available. We aimed to prospectively evaluate the role of CEUS in characterization of pancreatic lesions.58 patients (38 male, median age 73 yrs) with 63 histologically proven pancreatic lesions detectable at the US were investigated. The final diagnosis were: 18 adenocarcinoma, 5 insulinomas, 8 mass forming pancreatitis (MFP), 6 intraductal papillary mucinous tumors [IPMT], 13 pseudocystis, 8 serous cystadenoma [SCA] and 5 mucinous cystadenoma [MCA].

Contrast-Enhanced Endoscopic Ultrasonography (CE-EUS) Improves Visualization of Pancreatic Vasculature

Neovascularization in neoplasms may enable improved visualization with EUS if a contrast agent is used. Lipid microspheres are an established diagnostic tool for increasing contrast of vascular structures in echocardiography. Aim: To evaluate the potential utility of contrast enhanced EUS (CE-EUS) in the characterization of pancreatic lesions in a porcine model. Methods: 3 anesthesized 50kg pigs underwent EUS. For optimal visualization, the ultrasound mechanical index was decreased to 0.3. 2 mL of Perflutren lipid microspheres (5uL/kg) (Definity®) were administered by peripheral IV. The pancreas and peri-pancreatic vessels were re-imaged. To create an animal model of pancreatic microvascular disruption, 0.5 mL of 50% ethanol plus purified carbon particle solution (GI Spot®) was injected with an Olympus® 22g EUS-FNA needle into the body of the pancreas. 24–48 hours post ethanol-injection, the pancreas was re-evaluated. Standard and CE-EUS imaging of the pancreas were compared. Post-mortem examination was performed. Results: With conventional EUS, there was minimal color flow within the pancreatic parenchyma. Within 30 seconds of injection of microspheres, the microvasculature of the pancreas was well visualized with increased color flow. The microspheres were also well seen in the peri-pancreatic vessels. The mean duration CE-EUS visualization was 2.29 minutes. Standard EUS imaging showed a subtle 1cm hypoechoic region in the ethanol-treated area. Color and power doppler EUS of this region did not reveal any signal or blood flow. After microsphere injection, color Doppler EUS revealed marked contrast enhancement of normal pancreatic parenchyma from the alcohol-treated area, which on groß examination corresponded to the marked necrotic area. Conclusions: CE-EUS with microspheres improves EUS visualization of the pancreatic microvasculature and delineation of altered vascular perfusion.

Characterization of pancreatic lesions from MT-tgfα, Ela-myc and MT-tgfα/Ela-myc single and double transgenic mice

In order to identify good animal models for investigating therapeutic and preventive strategies for pancreatic cancer, we analyzed pancreatic lesions from several transgenic models and made a series of novel findings. Female MT-tgfα mice of the MT100 line developed pancreatic proliferation, acinar-ductal metaplasia, multilocular cystic neoplasms, ductal adenocarcinomas and prominent fibrosis, while the lesions in males were less severe. MT-tgfα-ES transgenic lines of both sexes developed slowly progressing lesions that were similar to what was seen in MT100 males. In both MT100 and MT-tgfα-ES lines, TGFα transgene was expressed mainly in proliferating ductal cells. Ela-myc transgenic mice with a mixed C57BL/6, SJL and FVB genetic background developed pancreatic tumors at 2–7 months of age, and half of the tumors were ductal adenocarcinomas, similar to what was reported originally by Sandgren et al [1]. However, in 20% of the mice, the tumors metastasized to the liver. MT100/Ela-myc and MT-tgfα-ES/Ela-myc double transgenic mice developed not only acinar carcinomas and mixed carcinomas as previously reported but also various ductal-originated lesions, including multilocular cystic neoplasms and ductal adenocarcinomas. The double transgenic tumors were more malignant and metastasized to the liver at a higher frequency (33%) compared with the Ela-myc tumors. Sequencing of the coding region of p16ink4, k-ras and Rb cDNA in small numbers of pancreatic tumors did not identify mutations. The short latency for tumor development, the variety of tumor morphology and the liver metastases seen in Ela-myc and MT-tgfα/Ela-myc mice make these animals good models for investigating new therapeutic and preventive strategies for pancreatic cancer.