Preoperative Imaging Evaluation after Downstaging of Pancreatic Ductal Adenocarcinoma: A Multi-Center Study.

INTRODUCTION: Evaluation of pancreatic ductal adenocarcinoma (PDAC) after chemoradiotherapy downstaging is challenging due to computed tomography (CT) overestimation of tumor extension and residual vascular involvement, limiting access to surgery to some patients with potentially resectable tumors. With this study, we wanted to assess which radiological findings are most reliable at pre-operative imaging in the evaluation of PDAC after chemoradiotherapy in order to achieve complete resection. METHODS: We retrospectively enrolled 71 patients with locally advanced and borderline resectable PDAC who underwent neoadjuvant chemoradiotherapy. Pre-operative CT or magnetic resonance (MR) have been evaluated by three radiologists to assess major qualitative and quantitative parameters of lesions. Accuracy, sensitivity, and specificity compared to anatomopathological results were evaluated for each parameter. Cohen's K-coefficient has been calculated to evaluate the inter-observer agreement (IOA). Both single and consensus lecture have been tested. Different dimensional cut-offs were tested to categorize tumors according to their major axis and to compare with anatomopathological diameter, tumor persistence, and margin infiltration. RESULTS: A 25 mm cut-off was 67% sensitive, 90% specific, and 77% accurate in assessing real tumor dimension. 25 mm cut-off reported a 64% sensitivity, 78% specificity, and 69% accuracy in assessing R0 resection. Each 5 mm increment of major axis dimension there is an odds ratio (OR) 1.79 (95% CI 1.13⁻2.80, p = 0.012) for R+ resection. Imaging presence of the perivascular cuff is not associated with tumor persistence and resection margin infiltration (p = 0.362). Lesion enhancement and pattern homogeneity were not accurate in determining tumor persistence. IOA was generally poor to fair, except for >25 mm cut-off classification where IOA was moderate. Diagnostic accuracy is superior in consensus lecture rather than single lecture. CONCLUSION: Imaging methods tend to underestimate PDAC resectability after neoadjuvant-CRT. IOA is poor to fair in evaluating most of the qualitative parameters of downstaged pancreatic adenocarcinoma. Surgery should be considered for downstaged borderline resectable PDACs, independently from perivascular cuff presence, especially for tumors smaller than 25 mm.

Intravoxel incoherent motion diffusion-weighted MR imaging of solid pancreatic masses: reliability and usefulness for characterization.

PURPOSE: IVIM-DW imaging has shown potential usefulness in the study of pancreatic lesions. Controversial results are available regarding the reliability of the measurements of IVIM-derived parameters. The aim of this study was to evaluate the reliability and the diagnostic potential of IVIM-derived parameters in differentiation among focal solid pancreatic lesions and normal pancreas (NP). METHODS: Fifty-seven patients (34 carcinomas-PDACs, 18 neuroendocrine neoplasms-panNENs, and 5 autoimmune pancreatitis-AIP) and 50 subjects with NP underwent 1.5-T MR imaging including IVIM-DWI. Images were analyzed by two independent readers. Apparent diffusion coefficient (ADC), slow component of diffusion (D), incoherent microcirculation (Dp), and perfusion fraction (f) were calculated. Interobserver reliability was assessed with intraclass correlation coefficient (ICC). A Kruskal-Wallis H test with Steel-Dwass post hoc test was used for comparison. The diagnostic performance of each parameter was evaluated through receiver operating characteristic (ROC) curve analysis. RESULTS: Overall interobserver agreement was excellent (ICC = 0.860, 0.937, 0.968, and 0.983 for ADC, D, Dp, and f). D, Dp, and f significantly differed among PDACs and panNENs (p = 0.002, < 0.001, and < 0.001), albeit without significant difference at the pairwise comparison of ROC curves (p = 0.08-0.74). Perfusion fraction was higher in AIP compared with PDACs (p = 0.024; AUC = 0.735). Dp and f were higher in panNENs compared with AIP (p = 0.029 and 0.023), without differences at ROC analysis (p = 0.07). CONCLUSIONS: IVIM-derived parameters have excellent reliability and could help in differentiation among solid pancreatic lesions and NP.

Imaging presentation of pancreatic neuroendocrine neoplasms.

Pancreatic neuroendocrine neoplasms (P-NENs) are the second most common solid pancreatic neoplasms. P-NENs have a wide range of imaging features presentations and they can be detected with typical and atypical imaging presentations. Typical and atypical appearances can be explained by pathologic correlations. P-NENs are generally hypervascular lesions, showing a typical enhancement behavior after contrast media injection during imaging methods, but they could also have different imaging features, creating some difficulty in differential diagnosis. For this reason, radiologists should be aware of different imaging presentations of these neoplasms. Radiological evaluation has a critical role in P-NENs identification, characterization, and staging of these neoplasms, especially in those cases in which surgery is the treatment of choice. The present paper shows, indicating the underlying pathologic correlations, typical and atypical presentations of NENs. KEY POINTS: • P-NENs have a wide range of imaging features presentations, typical and atypical. • Pathology could help in better understanding the typical P-NENs appearance at imaging. • P-NENs are generally hypervascular lesions. • Radiological evaluation has a critical role in P-NENs identification and management. • Radiologists should know every type of different imaging presentation of P-NENs to better diagnose these kinds of lesions.

Can histogram analysis of MR images predict aggressiveness in pancreatic neuroendocrine tumors?

OBJECTIVES: To evaluate MRI derived whole-tumour histogram analysis parameters in predicting pancreatic neuroendocrine neoplasm (panNEN) grade and aggressiveness. METHODS: Pre-operative MR of 42 consecutive patients with panNEN >1 cm were retrospectively analysed. T1-/T2-weighted images and ADC maps were analysed. Histogram-derived parameters were compared to histopathological features using the Mann-Whitney U test. Diagnostic accuracy was assessed by ROC-AUC analysis; sensitivity and specificity were assessed for each histogram parameter. RESULTS: ADCentropy was significantly higher in G2-3 tumours with ROC-AUC 0.757; sensitivity and specificity were 83.3 % (95 % CI: 61.2-94.5) and 61.1 % (95 % CI: 36.1-81.7). ADCkurtosis was higher in panNENs with vascular involvement, nodal and hepatic metastases (p= .008, .021 and .008; ROC-AUC= 0.820, 0.709 and 0.820); sensitivity and specificity were: 85.7/74.3 % (95 % CI: 42-99.2 /56.4-86.9), 36.8/96.5 % (95 % CI: 17.2-61.4 /76-99.8) and 100/62.8 % (95 % CI: 56.1-100/44.9-78.1). No significant differences between groups were found for other histogram-derived parameters (p >.05). CONCLUSIONS: Whole-tumour histogram analysis of ADC maps may be helpful in predicting tumour grade, vascular involvement, nodal and liver metastases in panNENs. ADCentropy and ADCkurtosis are the most accurate parameters for identification of panNENs with malignant behaviour. KEY POINTS: • Whole-tumour ADC histogram analysis can predict aggressiveness in pancreatic neuroendocrine neoplasms. • ADC entropy and kurtosis are higher in aggressive tumours. • ADC histogram analysis can quantify tumour diffusion heterogeneity. • Non-invasive quantification of tumour heterogeneity can provide adjunctive information for prognostication.

Tumor thrombosis: a peculiar finding associated with pancreatic neuroendocrine neoplasms. A pictorial essay.

While abutment, encasement or vessel occlusion are identified in most patients with a pancreatic tumor, tumor thrombosis is an uncommon finding. In particular, there are no description in the literature of tumor thrombosis associated with ductal adenocarcinoma, the most common pancreatic tumor. On the other hand, surgical series reveal that tumor thrombosis is associated with about 5% of pancreatic neuroendocrine neoplasms (PanNENs), and literature data suggest that this finding is frequently underreported on pre-operative imaging examinations. Tumor thrombosis may be clinically relevant, causing splenoportomesenteric hypertension, possibly responsible for life-threatening upper gastrointestinal bleeding. Bland thrombosis caused by direct infiltration of peri-pancreatic vessels frequently determines surgical unresectability, even in neuroendocrine tumors; on the opposite, tumor thrombosis associated with PanNENs do not exclude surgery per se, even though both morbidity and mortality can be increased by such condition. Considering the favorable prognosis of PanNENs and the frequent need to treat tumor thrombosis in order to prevent complications or to relieve symptoms, it is of paramount importance for radiologists the knowledge of the variety of findings associated with tumor thrombosis in PanNENs.

Pancreatic neuroendocrine neoplasms: Magnetic resonance imaging features according to grade and stage.

AIM: To describe magnetic resonance (MR) imaging features of pancreatic neuroendocrine neoplasms (PanNENs) according to their grade and tumor-nodes-metastases stage by comparing them to histopathology and to determine the accuracy of MR imaging features in predicting their biological behavior. METHODS: This study was approved by our institutional review board; requirement for informed patient consent was waived due to the retrospective nature of the study. Preoperative MR examinations of 55 PanNEN patients (29 men, 26 women; mean age of 57.6 years, range 21-83 years) performed between June 2013 and December 2015 were reviewed. Qualitative and quantitative features were compared between tumor grades and stages determined by histopathological analysis. RESULTS: Ill defined margins were more common in G2-3 and stage III-IV PanNENs than in G1 and low-stage tumors (P < 0.001); this feature had high specificity in the identification of G2-3 and stage III-IV tumors (90.3% and 96%, 95%CI: 73.1-97.5 and 77.7-99.8). The mean apparent diffusion coefficient value was significantly lower in G2-3 and stage III-IV lesions compared to well differentiated and low-stage tumors (1.09 × 10-3 mm2/s vs 1.45 × 10-3 mm2/s and 1.10 × 10-3 mm2/s vs 1.53 × 10-3 mm2/s, P = 0.003 and 0.001). Receiving operator characteristic analysis determined optimal cut-offs of 1.21 and 1.28 × 10-3 mm2/s for the identification of G2-3 and stage III-IV tumors, with sensitivity and specificity values of 70.8/80.7% and 64.5/64% (95%CI: 48.7-86.6/60-92.7 and 45.4-80.2/42.6-81.3). CONCLUSION: MR features of PanNENs vary according to their grade of differentiation and their stage at diagnosis and could predict the biological behavior of these tumors.

Digital Subtraction of Magnetic Resonance Images Improves Detection and Characterization of Pancreatic Neuroendocrine Neoplasms.

OBJECTIVE: The aim of this study was to evaluate the usefulness of digital image subtraction of contrast-enhanced magnetic resonance (MR) images for detection and characterization of pancreatic neuroendocrine neoplasms (PanNENs). METHODS: Magnetic resonance examinations of 50 histologically verified PanNENs were retrospectively evaluated by 2 radiologists; 50 ductal adenocarcinomas were included as a control group. Late arterial phase images and correspondent subtracted images were analyzed. Tumor detectability on a subjective 3-point scale and contrast-to-noise ratios were compared across sequences using paired Student t tests. Tumor signal intensity was compared between sequences using χ or Fisher exact tests. RESULTS: Subjective conspicuity and contrast-to-noise ratios of PanNENs were significantly higher on subtracted images compared with correspondent late arterial phase images (P < 0.001 and P = 0.002). The rate of clearly hyperenhancing PanNENs was higher on subtracted images compared with arterial phase images (76% vs 36%). CONCLUSIONS: Digital image subtraction improves tumor conspicuity and allows better characterization of PanNENs compared with late arterial phase images.

Oncocytic Intraductal Papillary Mucinous Neoplasms of the Pancreas: Imaging and Histopathological Findings.

OBJECTIVES: To evaluate and correlate computed tomography/magnetic resonance findings and histopathologic features of oncocytic intraductal papillary mucinous neoplasms (O-IPMNs). METHODS: Computed tomography/magnetic resonance examinations and resection specimens of 16 O-IPMNs were retrospectively reviewed. Qualitative and quantitative imaging features were analyzed according to "worrisome features" and "high risk stigmata." Correlations between radiological and histopathological findings were evaluated using Fisher test. RESULTS: Most O-IPMNs (75%) presented as large mixed- or main duct-type lesions (mean size, 56.9 mm; range, 20-180); all branch-duct type lesions were larger than 3 cm. Ten lesions presented main pancreatic duct dilation of 10 mm or greater. Solid enhancing nodules were found in 10 cases. Two lesions presented foci of invasion at histopathologic analysis, the remaining presented high-grade dysplasia. Neither invasive carcinoma nor nodal metastases were found. No significant correlations were found between radiological predictors of malignancy and histopathological features. CONCLUSIONS: Oncocytic tumors are rare subtypes of pancreatic IPMN, whose imaging features are similar to other IPMN subtypes. Imaging predictors of malignancy as large size and huge solid internal nodules are frequently encountered in O-IPMNs; despite this, these features are not correlated with histopathological findings, being probably inapplicable to O-IPMNs.

Variation of tumoral marker after radiofrequency ablation of pancreatic adenocarcinoma.

BACKGROUND: To evaluate the correlation between variations of CA 19.9 blood levels and the entity of necrosis at CT after radiofrequency ablation (RFA) of unresectable pancreatic adenocarcinoma. METHODS: In this study, from June 2010 to February 2014, patients with diagnosis of unresectable and not metastatic pancreatic ductal adenocarcinoma, expressing tumor marker CA 19.9, treated with RFA procedure were included. All these patients underwent RFA. CT study was performed 1 week after RFA. The dosage of CA 19.9 levels was performed 1 month after RFA. Features of necrosis at CT, as mean entity, density and necrosis percentages compared to the original lesion, were evaluated and compared by using t-test with CA 19.9 blood levels variations after RFA procedure. RESULTS: In this study were included 51 patients with diagnosis of unresectable and not metastatic pancreatic ductal adenocarcinoma, expressing tumor marker CA 19.9, treated with RFA procedure and with CT study and CA 19.9 available for analysis. After the procedure, CA 19.9 blood levels reduced in 24/51 (47%), remained stable in 10/51 (20%) and increased in 17/51 (33%). In patients with CA 19.9 levels reduced, the tumor marker were reduced less than 20% in 4/24 (17%) and more than 20% in 20/24 (83%); instead the tumor marker were reduced less than 30% in 8/24 (33%) and more than 30% in 16/24 (67%). At CT scan necrotic area density difference was not statistically significant. Also there was no statistically significant difference among the mean area, the mean volume and the mean ablation volume in percentage related to the treated tumor among the three different groups of patients divided depending on the CA 19.9 blood levels. But a tendency to a statistically significant difference was found in comparing the mean percentage of ablation volume between two subgroups of patients with a decrease of CA 19.9 levels with less or more than 20% reduction of tumor markers and between two subgroups with less or more than 30% reduction of CA 19.9 levels. CONCLUSIONS: RFA of unresectable pancreatic adenocarcinoma induces reduction of CA 19.9 blood levels in about half of the cases.

Pancreatic Neuroendocrine Neoplasms: Clinical Value of Diffusion-Weighted Imaging.

BACKGROUND/AIMS: Diffusion-weighted imaging (DWI) can depict random motions of water molecules in biological tissues during magnetic resonance (MR) examinations. Few papers have tested its application to pancreatic neuroendocrine neoplasms (PanNENs). The aim of this paper is to assess the clinical value of DWI regarding the identification and characterization of PanNENs and diagnosis of liver metastases. METHODS: Preoperative MR examinations of 30 PanNEN patients were retrospectively reviewed; 30 patients with pathologically proven pancreatic ductal adenocarcinoma (PDAC) were included to compare the imaging features. Qualitative and quantitative MR features were compared between histotypes. A blinded-reader comparison of diagnostic confidence for PanNENs and liver metastases was conducted on randomized image sets. All results were compared with pathological data. RESULTS: PanNEN conspicuity was higher on DW images compared to conventional MR sequences. DWI had higher detection rates for PanNENs than had conventional sequences (93.3 vs. 71.1%). Sharp margins and absence of main pancreatic duct/common bile duct dilation and chronic pancreatitis were more common among PanNENs as compared to PDACs. Arterial iso- or hyperenhancement and portal hyperenhancement were more frequent within PanNENs as compared to PDACs. No differences between histotypes were found for quantitative features. Arterial-phase images had the highest interobserver agreement for the diagnosis of PanNEN (Cohen's κ = 0.667). DWI provided the highest detection rate for liver metastases as well as excellent interobserver agreement for the diagnosis of liver metastases (κ = 0.932), with good accuracy (AUC = 0.879-0.869). CONCLUSION: DWI has clinical value regarding the identification of PanNENs and the diagnosis of liver metastases, while conventional MR sequences are fundamental for their characterization.

Diffusion-weighted imaging of pancreatic cancer.

Magnetic resonance imaging (MRI) is a reliable and accurate imaging method for the evaluation of patients with pancreatic ductal adenocarcinoma (PDAC). Diffusion-weighted imaging (DWI) is a relatively recent technological improvement that expanded MRI capabilities, having brought functional aspects into conventional morphologic MRI evaluation. DWI can depict the random diffusion of water molecules within tissues (the so-called Brownian motions). Modifications of water diffusion induced by different factors acting on the extracellular and intracellular spaces, as increased cell density, edema, fibrosis, or altered functionality of cell membranes, can be detected using this MR sequence. The intravoxel incoherent motion (IVIM) model is an advanced DWI technique that consent a separate quantitative evaluation of all the microscopic random motions that contribute to DWI, which are essentially represented by molecular diffusion and blood microcirculation (perfusion). Technological improvements have made possible the routine use of DWI during abdominal MRI study. Several authors have reported that the addition of DWI sequence can be of value for the evaluation of patients with PDAC, especially improving the staging; nevertheless, it is still unclear whether and how DWI could be helpful for identification, characterization, prognostic stratification and follow-up during treatment. The aim of this paper is to review up-to-date literature data regarding the applications of DWI and IVIM to PDACs.

Prognostication and response assessment in liver and pancreatic tumors: The new imaging.

Diffusion-weighted imaging (DWI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and perfusion computed tomography (CT) are technical improvements of morphologic imaging that can evaluate functional properties of hepato-bilio-pancreatic tumors during conventional MRI or CT examinations. Nevertheless, the term "functional imaging" is commonly used to describe molecular imaging techniques, as positron emission tomography (PET) CT/MRI, which still represent the most widely used methods for the evaluation of functional properties of solid neoplasms; unlike PET or single photon emission computed tomography, functional imaging techniques applied to conventional MRI/CT examinations do not require the administration of radiolabeled drugs or specific equipments. Moreover, DWI and DCE-MRI can be performed during the same session, thus providing a comprehensive "one-step" morphological and functional evaluation of hepato-bilio-pancreatic tumors. Literature data reveal that functional imaging techniques could be proposed for the evaluation of these tumors before treatment, given that they may improve staging and predict prognosis or clinical outcome. Microscopic changes within neoplastic tissues induced by treatments can be detected and quantified with functional imaging, therefore these techniques could be used also for post-treatment assessment, even at an early stage. The aim of this editorial is to describe possible applications of new functional imaging techniques apart from molecular imaging to hepatic and pancreatic tumors through a review of up-to-date literature data, with a particular emphasis on pathological correlations, prognostic stratification and post-treatment monitoring.

Uncommon presentations of common pancreatic neoplasms: a pictorial essay.

Pancreatic neoplasms are a wide group of solid and cystic lesions with different and often characteristic imaging features, clinical presentations, and management. Among solid tumors, ductal adenocarcinoma is the most common: it arises from exocrine pancreas, comprises about 90% of all pancreatic neoplasms, and generally has a bad prognosis; its therapeutic management must be multidisciplinary, involving surgeons, oncologists, gastroenterologists, radiologists, and radiotherapists. The second most common solid pancreatic neoplasms are neuroendocrine tumors: they can be divided into functioning or non-functioning and present different degrees of malignancy. Cystic pancreatic neoplasms comprise serous neoplasms, which are almost always benign, mucinous cystic neoplasms and intraductal papillary mucinous neoplasms, which can vary from benign to frankly malignant lesions, and solid pseudopapillary tumors. Other pancreatic neoplasms, such as lymphoma, metastases, or pancreatoblastoma, are rarely seen in clinical practice and have different and sometimes controversial managements. Rare clinical presentations and imaging appearance of the most common pancreatic neoplasms, both solid and cystic, are more frequently seen and clinically relevant than rare pancreatic tumors; their pathologic and radiologic appearances must be known to improve their management. The purpose of this paper is to present some rare or uncommon clinical and radiological presentations of common pancreatic neoplasms providing examples of multi-modality imaging approach with pathologic correlations, thus describing the histopathological bases that can explain the peculiar imaging features, in order to avoid relevant misdiagnosis and to improve lesion management.