Comprehensive Characterization of Intraductal Oncocytic Papillary Neoplasm of the Pancreas: A Systematic and Critical Review.

Intraductal oncocytic papillary neoplasm (IOPN) of the pancreas is a recently recognized pancreatic tumor. Here, we aimed to determine its most essential features with the systematic review tool. PubMed, Scopus, and Embase were searched for studies reporting data on pancreatic IOPN. The clinicopathologic, immunohistochemical, and molecular data were extracted and summarized. Then, a comparative analysis of the molecular alterations of IOPN with those of pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasm from reference cohorts (including The Cancer Genome Atlas) was conducted. The key findings from 414 IOPNs were as follows: 1) The male-to-female ratio was 1.5:1. Pancreatic head was the most common site (131/237; 55.3%), but a diffuse tumor extension involving more than one pancreatic segment was described in about 1 out of 5 cases (49/237; 20.6%). The mean size was 45.5 mm. An associated invasive carcinoma was present in 50% of cases (168/336). In those cases, most tumors were pT1 or pT2 and pN0 (>80%), and vascular invasion was uncommon (20.6%). Regarding survival, more than 90% of patients were alive after surgical resection. 2) Immunohistochemical and molecular features were as follows. The most commonly expressed mucins were MUC5AC (110/112; 98.2%) and MUC6 (78/84; 92.8%). Compared with pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasm, the classic pancreatic drivers KRAS, TP53, CDKN2A, SMAD4, and GNAS were less altered in IOPN (P < .01). Moreover, fusions involving PRKACA or PRKACB gene were detected in all of the 68 cases examined, with PRKACB::ATP1B1 being the most common (27/68 cases; 39.7%). These genomic events emerged as an entity-defining molecular alteration of IOPN (P < .01). Thus, such fusions represent a promising biomarker for diagnostic purposes. Recent evidence also suggests their role in influencing the acquisition of oncocytic morphology. IOPN is a distinct pancreatic neoplasm with specific clinicopathologic and molecular features. Considering the clinical or prognostic implications, its recognition is essential for pathologists and, ultimately, patients' management.

Dual-Energy CT for Detecting Painful Knee Prosthesis Loosening.

Background Dual-energy CT (DECT) is an alternative to radiography and single-energy CT (SECT) for detecting prosthesis-related complications. Purpose To compare the diagnostic performance of DECT, SECT, and radiography for knee prosthesis loosening, with use of surgery or imaging follow-up reference standards. Materials and Methods In this prospective single-center study from December 2018 to June 2021, participants with unilateral painful knee prostheses underwent radiographic, SECT, and DECT imaging. Five blinded readers, four radiologists, and one orthopedic surgeon evaluated the images. Prosthesis loosening was diagnosed by a periprosthetic lucent zone greater than 2 mm. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of each method were determined and compared with use of a multireader multicase analysis. Results There were 92 study participants (mean age ± SD, 70 years ± 9.4; 67 women) evaluated. Tibial and femoral loosening were diagnosed in 47 and 24 participants, respectively. For the tibia, mean sensitivity and specificity for arthroplasty loosening were 88% and 91%, respectively, for DECT, 73% and 78% for SECT, and 68% and 81% for radiography. For the tibia, DECT demonstrated similar diagnostic performance (AUC, 0.90) to SECT (AUC: 0.90 vs AUC: 0.87, respectively; P = .13) but was superior to radiography (AUC: 0.90 vs AUC: 0.82; P = .002). Overall diagnostic performance of DECT (AUC, 0.87) for the femur was superior to both SECT and radiography (P < .001). Conclusion Dual-energy CT had generally better diagnostic performance in detecting loosening of tibial and femoral components after total knee arthroplasty compared with single-energy CT or radiography. Clinical trial registration no. 2942 © RSNA, 2022.

Assessment of arterial-phase hyperenhancement and late-phase washout of hepatocellular carcinoma-a meta-analysis of contrast-enhanced ultrasound (CEUS) with SonoVue® and Sonazoid®.

OBJECTIVES: The recognition of arterial phase hyperenhancement (APHE) and washout during the late phase is key for correct diagnosis of hepatocellular carcinoma (HCC) with contrast-enhanced ultrasound (CEUS). This meta-analysis was conducted to compare SonoVue®-enhanced and Sonazoid®-enhanced ultrasound in the assessment of HCC enhancement and diagnosis. METHODS: Studies were included in the analysis if they reported data for HCC enhancement in the arterial phase and late phase for SonoVue® or in the arterial phase and Kupffer phase (KP) for Sonazoid®. Forty-two studies (7502 patients) with use of SonoVue® and 30 studies (2391 patients) with use of Sonazoid® were identified. In a pooled analysis, the comparison between SonoVue® and Sonazoid® CEUS was performed using chi-square test. An inverse variance weighted random-effect model was used to estimate proportion, sensitivity, and specificity along with 95% confidence interval (CI). RESULTS: In the meta-analysis, the proportion of HCC showing APHE with SonoVue®, 93% (95% CI 91-95%), was significantly higher than the proportion of HCC showing APHE with Sonazoid®, 77% (71-83%) (p < 0.0001); similarly, the proportion of HCC showing washout at late phase/KP was significantly higher with SonoVue®, 86% (83-89%), than with Sonazoid®, 76% (70-82%) (p < 0.0001). The sensitivity and specificity for the detection of APHE plus late-phase/KP washout detection in HCC were also higher with SonoVue® than with Sonazoid® (sensitivity 80% vs 52%; specificity 80% vs 73% in studies within unselected patient populations). CONCLUSION: APHE and late washout in HCC are more frequently observed with SonoVue® than with Sonazoid®. This may affect the diagnostic performance of CEUS in the diagnosis of HCCs. CLINICAL RELEVANCE STATEMENT: Meta-analysis data show the presence of key enhancement features for diagnosis of hepatocellular carcinoma is different between ultrasound contrast agents, and arterial hyperenhancement and late washout are more frequently observed at contrast-enhanced ultrasound with SonoVue® than with Sonazoid®. KEY POINTS: • Dynamic enhancement features are key for imaging-based diagnosis of HCC. • Arterial hyperenhancement and late washout are more often observed in HCCs using SonoVue®-enhanced US than with Sonazoid®. • The existing evidence for contrast-enhanced US may need to be considered being specific to the individual contrast agent.

Ultrasound-derived fat fraction for detection of hepatic steatosis and quantification of liver fat content.

PURPOSE: To compare ultrasound (US) and US-derived fat fraction (UDFF) with magnetic resonance proton density fat fraction (MRI-PDFF) for the detection of hepatic steatosis and quantification of liver fat content. MATERIALS AND METHODS: Between October and December 2022, 149 patients scheduled for an abdominal MRI agreed to participate in this study and underwent MRI-PDFF, US and UDFF. Inclusion criteria were: (a) no chronic liver disease or jaundice; (b) no MRI motion artifacts; (c) adequate liver examination at US. Exclusion criteria were: (a) alcohol abuse, chronic hepatitis, cirrhosis, or jaundice; (b) MRI artifacts or insufficient US examination. The median of 10 MRI-PDFF and UDFF measurements in the right hepatic lobe was analyzed. UDFF and MRI-PDFF were compared by Bland-Altman difference plot and Pearson's test. Sensitivity, specificity, positive and negative predictive values, accuracy, and area under the receiver-operator curve (AUC-ROC) of US and UDFF were calculated using an MRI-PDFF cut-off value of 5%. p values ≤ 0.05 were statistically significant. RESULTS: 122 patients were included (61 men, mean age 60 years, standard deviation 15 years). The median MRI-PDFF value was 4.1% (interquartile range 2.9-6); 37.7% patients had a median MRI-PDFF value ≥ 5%. UDFF and MRI-PDFF had high agreement (p = 0.11) and positive correlation (⍴ = 0.81, p < 0.001). UDFF had a higher diagnostic value than US for the detection of steatosis, with AUC-ROCs of 0.75 (95% CI 0.65, 0.84) and 0.53 (95% CI 0.42, 0.64), respectively. CONCLUSIONS: UDFF reliably quantifies liver fat content and improves the diagnostic value of US for the detection of hepatic steatosis.

Dual-Tracer (68Ga-DOTATOC and 18F-FDG-)-PET/CT Scan and G1-G2 Nonfunctioning Pancreatic Neuroendocrine Tumors: A Single-Center Retrospective Evaluation of 124 Nonmetastatic Resected Cases.

INTRODUCTION: The combined use of 68gallium (68Ga)-DOTA-peptides and 18fluorine-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) scans in the workup of pancreatic neuroendocrine tumors (PanNETs) is controversial. This study aimed at assessing both tracers' capability to identify tumors and to assess its association with pathological predictors of recurrence. METHODS: Prospectively collected, preoperative, dual-tracer PET/CT scan data of G1-G2, nonmetastatic, PanNETs that underwent surgery between January 2013 and October 2019 were retrospectively analyzed. RESULTS: The final cohort consisted of 124 cases. There was an approximately equal distribution of males and females (50.8%/49.2%) and G1 and G2 tumors (49.2%/50.8%). The disease was detected in 122 (98.4%) and 64 (51.6%) cases by 68Ga-DOTATOC and by 18F-FDG PET/CT scans, respectively, with a combined sensitivity of 99.2%. 18F-FDG-positive examinations found G2 tumors more often than G1 (59.4 vs. 40.6%; p = 0.036), and 18F-FDG-positive PanNETs were larger than negative ones (median tumor size 32 mm, interquartile range [IQR] 21 vs. 26 mm, IQR 20; p = 0.019). The median Ki67 for 18F-FDG-positive and -negative examinations was 3 (IQR 4) and 2 (IQR 4), respectively (p = 0.029). At least 1 pathological predictor of recurrence was present in 74.6% of 18F-FDG-positive cases (vs. 56.7%; p = 0.039), whereas this was not found when dichotomizing the PanNETs by their dimensions (≤/>20 mm). None of the 2 tracers predicted nodal metastasis. The receiver operating characteristic curve analysis showed that 18F-FDG uptake higher than 4.2 had a sensitivity of 49.2% and specificity of 73.3% for differentiating G1 from G2 (AUC = 0.624, p = 0.009). CONCLUSION: The complementary adoption of 68Ga-DOTATOC and 18F-FDG tracers may be valuable in the diagnostic workup of PanNETs despite not being a game-changer for the management of PanNETs ≤20 mm.

US-Guided Percutaneous Radiofrequency Ablation of Locally Advanced Pancreatic Adenocarcinoma: A 5-Year High-Volume Center Experience.

PURPOSE: The aim of this study was to investigate the safety and effectiveness of percutaneous radiofrequency ablation (RFA) in locally advanced pancreatic cancer (LAPC) of the pancreatic body by assessing the overall survival of patients and evaluating the effects of the procedure in the clinical and radiological follow-up. MATERIALS AND METHODS: Patients with unresectable LAPC after failed chemoradiotherapy for at least six months were retrospectively included. Percutaneous RFA was performed after a preliminary ultrasound (US) feasibility evaluation. Contrast-enhanced computed tomography (CT) and CA 19.9 sampling were performed before and 24 hours and 30 days after the procedure to evaluate the effects of the ablation. Patients were followed-up after discharge considering the two main endpoints: procedure-related complications and death. RESULTS: 35 patients were included, 5 were excluded. All patients underwent RFA with no procedure-related complications reported. The mean size of tumors was 49 mm before treatment. The mean dimension of the ablated necrotic zone was 32 mm, with a mean extension of 65 % compared to the whole tumor size. Tumor density was statistically reduced one day after the procedure (p < 0.001). The mean CA 19.9 levels before and 24 hours and 30 days after the procedure were 285.8 U/mL, 635.2 U/mL, and 336.0 U/mL, respectively, with a decrease or stability at the 30-day evaluation in 80 % of cases. The mean survival was 310 (65-718) days. CONCLUSION: Percutaneous RFA of LAPC is a feasible technique in patients who cannot undergo surgery, with great debulking effects and a very low complication rate.

Cost-effectiveness analysis of including contrast-enhanced ultrasound in management of pancreatic cystic neoplasms.

PURPOSE: Pancreatic cystic neoplasms (PCN) management consists of non-invasive imaging studies (CT, MRI), with a high resource burden. We aimed to determine the cost-effectiveness of including contrast-enhanced ultrasound (CEUS) in the management of PCN without risk features. MATERIALS AND METHODS: By using a decision-tree model in a hypothetical cohort of patients, we compared management strategy including CEUS with the latest Fukuoka consensus, European and Italian guidelines. Our strategy for BD-IPMN/MCN < 1 cm includes 1 CEUS annually. For those between 1 and 2 cm, it includes CEUS 4 times/year during the first year, then 3 times/year for 4 years and then annually. For those between 2 and 3 cm, it comprises MRI twice/year during the first one, then alternating 2 CEUS and 1 MRI yearly. RESULTS: CEUS surveillance is the dominant strategy in all scenarios. CEUS surveillance average cost is 1,984.72 €, mean QALY 11.79 and mean ICER 181.99 €. If willingness to pay is 30,000 €, 45% of patients undergone CEUS surveillance of BDIPMN/MCN < 1 cm would be within budget. CONCLUSION: Guidelines strategies are very effective, but costs are relatively high from a policy perspective. CEUS surveillance may be a cost-effective strategy yielding a nearly high QALYs, an acceptable ICER, and a lower cost.

Liver metastases in pancreatic ductal adenocarcinoma: a predictive model based on CT texture analysis.

PURPOSE: To develop a predictive model for liver metastases in patients with pancreatic ductal adenocarcinoma (PDAC) based on textural features of the primary tumor extracted by computed tomography (CT) images. MATERIALS AND METHODS: Patients with a pathologically proved PDAC who underwent CT between December 2020 and January 2022 were retrospectively identified. Treatment-naïve patients were included. Sex, age, tumor size, vascular infiltration and 39 arterial and portal phase textural features were analyzed. The variables significantly correlated to tumor size according to the Pearson's product-moment correlation test were excluded from analysis; the remaining variables were compared between metastatic (M +) and non-metastatic (M-) patients using Fisher's or Mann-Whitney test. The features with a significant difference between groups were entered into a binomial logistic regression test to develop a predictive model for liver metastases. RESULTS: This study included 220 patients. Eight variables (tumor size, arterial HU_MAX, arterial GLRLM_LRLGE, arterial GLZLM_SZHGE, arterial GLZLM_LZLGE, portal GLCM_CORRELATION, portal GLRLM_LRLGE, and portal GLZLM_SZHGE) were significantly different between groups. The logistic regression model was statistically significant (χ2 = 81.6, p < .001) and correctly classified 80.9% of cases. Sensitivity, specificity, positive and negative predictive values of the model were 58.6%, 91.3%, 75.9% and 82.5%, respectively. The area under the ROC curve of the model was 0.850 (95% CI, 0.793-0.907). Tumor size, arterial HU_MAX, arterial GLZLM_SZHGE and portal GLCM_CORRELATION were significant predictors of the likelihood of liver metastases, with odds ratios of 1.1, 0.9, 1, and 1.49, respectively. CONCLUSIONS: CT texture analysis of PDAC can identify features that may predict the likelihood of liver metastases.

Magnetic resonance (MR) for mural nodule detection studying Intraductal papillary mucinous neoplasms (IPMN) of pancreas: Imaging-pathologic correlation.

PURPOSE: Magnetic Resonance (MR) is recommended to diagnose Intraductal Papillary Mucinous Neoplasms (IPMN) and in the follow-up of borderline lesions. The purpose of this work is to evaluate the diagnostic accuracy of dynamic MR with Diffusion Weighted Imaging (DWI) in the identification of mural nodules of pancreatic IPMN by using pathological analysis as gold standard. MATERIALS AND METHODS: Ninety-one preoperative MR with histopathological diagnosis of IPMN were reviewed by two radiologists. Presence, number and size of mural nodule, signal intensity of the nodule on T1-weighted imaging (T1-WI) after contrast medium administration and on DWI. Inter-observer agreement was evaluated. RESULTS: Significant correlation (p < 0.0001) were found for presence of nodules > 5 mm on MR and pathological specimen, size and number of mural nodules evaluated on pathological review and degree of dysplasia, size and number of mural nodules evaluated on MR and tumoral dysplasia, presence of nodule > 5 mm with enhancement after contrast medium administration and hyperintensity on DWI and degree of dysplasia. Interobserver agreement was moderate for the presence of mural nodule (K = 0.56), for the presence of high signal intensity on DWI (K = 0.57) and enhancement of mural nodule (K = 0.58). Apparent Diffusion Coefficient (ADC) map histogram analysis showed a correlation between Entropy of the entire cystic lesion and the degree of dysplasia (p < 0.034). CONCLUSIONS: MR with dynamic and DWI sequences was an accurate method for the identification of ≥ 5 mm solid nodules of the IPMNs and correlate with the lesion malignancy. Entropy, calculated from the histogram analysis of the IPMN ADC map, correlated with the lesion dysplasia.

Laser Treatment of Pancreatic Cancer with Immunostimulating Interstitial Laser Thermotherapy Protocol: Safety and Feasibility Results From Two Phase 2a Studies.

PURPOSE: Ablative techniques have emerged as new potential therapeutic options for patients with locally advanced pancreatic cancer (LAPC). We explored the safety and feasibility of using TRANBERG|Thermal Therapy System (Clinical Laserthermia Systems AB, Lund, Sweden) in feedback mode for immunostimulating Interstitial Laser Thermotherapy (imILT) protocol, the newest ablative technique introduced for the treatment of LAPC. METHODS: The safety and feasibility results after the use of imILT protocol treatment in 15 patients of a prospective series of postsystemic therapy LAPC in two high-volume European institutions, the General and Pancreatic Unit of the Pancreas Institute, of the University of Verona, Italy, and the Department of Surgical Oncology of the Institut Paoli-Calmettes of Marseille, France, were assessed. RESULTS: The mean age was 66 ± 5 years, with a mean tumor size of 34.6 (±8) mm. The median number of cycles of pre-imILT chemotherapy was 6 (6-12). The procedure was performed in 13 of 15 (86.6%) cases; indeed, in two cases, the procedure was not performed; in one, the procedure was considered technically demanding; in the other, liver metastases were found intraoperatively. In all treated cases, the procedure was completed. Three late pancreatic fistulas developed over four overall adverse events (26.6%) and were attributed to imILT. Mortality was nil. A learning curve is necessary to interpret and manage the laser parameters. CONCLUSIONS: Safety, feasibility, and device handling outcomes of using TRANBERG|Thermal Therapy System with temperature probes in feedback mode and imILT protocol on LAPC were not satisfactory. The metastatic setting may be appropriate to evaluate the hypothetic abscopal effect.#NCT02702986 and #NCT02973217.

Endoscopic Ultrasound Features Associated with Malignancy and Aggressiveness of Nonhypovascular Solid Pancreatic Lesions: Results from a Prospective Observational Study.

BACKGROUND AND STUDY AIMS: On contrast-enhanced imaging studies, nonhypovascular (i. e., isovascular and hypervascular) patterns can be observed in solid pancreatic lesions (SPLs) of different nature, prognosis, and management. We aimed to identify endoscopic ultrasound (EUS) features of nonhypovascular SPLs associated with malignancy/aggressiveness. The secondary aims were EUS tissue acquisition (EUS-TA) outcome and safety in this setting of patients. PATIENTS AND METHODS: This prospective observational study included patients with nonhypovascular SPLs detected on cross-sectional imaging and referred for EUS-TA. Lesion features (size, site, margins, echotexture, vascular pattern, and upstream dilation of the main pancreatic duct) were recorded. Malignancy/aggressiveness was determined by evidence of carcinoma at biopsy/surgical pathology, signs of aggressiveness (perineural invasion, lymphovascular invasion, and/or microscopic tumor extension/infiltration or evidence of metastatic lymph nodes) in the surgical specimen, radiologic detection of lymph nodes or distant metastases, and/or tumor growth > 5 mm/6 months. Uni- and multivariate analyses were performed to assess the primary aim. RESULTS: A total of 154 patients with 161 SPLs were enrolled. 40 (24.8 %) lesions were defined as malignant/aggressive. Irregular margins and size > 20 mm were independent factors associated with malignancy/aggressiveness (p < 0.001, OR = 5.2 and p = 0.003, OR = 2.1, respectively). However, size > 20 mm was not significant in the subgroup of other-than-neuroendocrine tumor (NET) lesions. The EUS-TA accuracy was 92 %, and the rate of adverse events was 4 %. CONCLUSION: Irregular margins on EUS are associated with malignancy/aggressiveness of nonhypovascular SPLs. Size > 20 mm should be considered a malignancy-related feature only in NET patients. EUS-TA is safe and highly accurate for differential diagnosis in this group of patients.

Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis and grading of pancreatic neuroendocrine tumors: a retrospective analysis of 110 cases.

BACKGROUND: Data on the reliability of the Ki-67 index and grading calculations from endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic neuroendocrine tumors (PanNETs) are controversial. We aimed to assess the accuracy of these data compared with histology. METHODS: Cytological analysis from EUS-FNA in patients with suspected PanNETs (n = 110) were compared with resection samples at a single institution. A minimum of 2000 cells were considered to be adequate for grading. Correlation and agreement between cytology and histology in grading and Ki-67 values, respectively, were investigated. Secondary outcomes included the diagnostic performance of EUS-FNA. RESULTS: EUS-FNA samples were adequate for PanNET diagnosis and PanNET grading in 98/110 (89.1 %) and 77/110 (70.0 %) patients, respectively; thus, 77 samples were adequate for comparing cytology vs. histology. There were 67 (62.0 %), 40 (36.4 %), and 1 (0.9 %) patients with a final diagnosis of G1, G2, and G3 tumors, respectively. EUS-FNA grading was concordant with surgical pathology in 81.8 % of patients; under- and overgrading occurred in 15.6 % and 2.6 %, respectively. The overall level of agreement for grading was moderate (Cohen's κ = 0.59, 95 % confidence interval [CI] 0.34 - 0.78). Spearman's rho for Ki-67 in tumors ≤ 20 mm and > 20 mm was strong and moderate, respectively (rho = 0.68, 95 %CI 0.47 - 0.83; rho = 0.59, 95 %CI 0.35 - 0.75). The Bland - Altman plot showed that the Ki-67 values were comparable and reproducible between the two measurements. CONCLUSIONS: Although they were not available for a significant number of patients, grading and Ki-67 values from cytology correlated with histology moderately to strongly.

Guidelines and Good Clinical Practice Recommendations for Contrast Enhanced Ultrasound (CEUS) in the Liver - Update 2020 - WFUMB in Cooperation with EFSUMB, AFSUMB, AIUM, and FLAUS.

The present, updated document describes the fourth iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS), first initiated in 2004 by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). The previous updated editions of the guidelines reflected changes in the available contrast agents and updated the guidelines not only for hepatic but also for non-hepatic applications.The 2012 guideline requires updating as previously the differences of the contrast agents were not precisely described and the differences in contrast phases as well as handling were not clearly indicated. In addition, more evidence has been published for all contrast agents. The update also reflects the most recent developments in contrast agents, including the United States Food and Drug Administration (FDA) approval as well as the extensive Asian experience, to produce a truly international perspective.These guidelines and recommendations provide general advice on the use of ultrasound contrast agents (UCA) and are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis to improve the management of patients.

The Evolution of Surgical Strategies for Pancreatic Neuroendocrine Tumors (Pan-NENs): Time-trend and Outcome Analysis From 587 Consecutive Resections at a High-volume Institution.

OBJECTIVE: The objective of the present analysis is 2-fold: first, to define the evolution of time trends on the surgical approach to pancreatic neuroendocrine neoplasms (Pan-NENs); second, to perform a complete analysis of the predictors of oncologic outcome. BACKGROUND: Reflecting their rarity and heterogeneity, Pan-NENs represent a clinical dilemma. In particular, there is a scarcity of data regarding their long-term follow-up after surgical resection. METHODS: From the Institutional Pan-NEN database, 587 resected cases from 1990 to 2015 were extracted. The time span was arbitrarily divided into 3 discrete clusters enabling a balanced comparison between patient groups. Analyses for predictors of recurrence and survival were performed, together with conditional survival analyses. RESULTS: Among the 587 resected Pan-NENs, 75% were nonfunctioning tumors, and 5% were syndrome-associated tumors. The mean age was 54 years (±14 years), and 51% of the patients were female. The median tumor size was 20 mm (range 4 to 140), 62% were G1, 32% were G2, and 4% were G3 tumors. Time trends analysis revealed that the number of resected Pan-NENs constantly increased, while the size (from 25 to 20 mm) and G1 proportion (from 65% to 49%) decreased during the study period. After a mean follow-up of 75 months, recurrence analysis revealed that nonfunctioning tumors, tumor grade, N1 status, and vascular invasion were all independent predictors of recurrence. Regardless of size, G1 nonfunctioning tumors with no nodal involvement and vascular invasion had a negligible risk of recurrence at 5 years. CONCLUSIONS: Pan-NENs have been increasingly diagnosed and resected during the last 3 decades, revealing reliable predictors of outcome. Functioning and nodal status, tumor grade, and vascular invasion accurately predict survival and recurrence with resulting implications for patient follow-up.

Patterns of Recurrence after Resection for Pancreatic Neuroendocrine Tumors: Who, When, and Where?

BACKGROUND/AIMS: Pancreatic neuroendocrine tumors (pan-NENs) represent an increasingly common indication for pancreatic resection, but there are few data regarding possible recurrence after surgery. The aim of the study was to describe the frequency, timing, and patterns of recurrence after resection for pan-NENs with consequent implications for postoperative follow-up. METHODS: We performed a retrospective analysis of pan-NENs resected between 1990 and 2015 at The Pancreas Institute, University of Verona Hospital Trust. Predictors of recurrence were assessed. Survival analysis was conducted using the Kaplan-Meier and conditional survival (CS) methods. RESULTS: The cohort consisted of 487 patients with a median follow-up of 71 months. Recurrence developed in 12.3%: 54 (11.1%) liver metastases, 11 (2.3%) local recurrence, 10 (2.1%) nodal recurrence, and 8 (1.6%) metastases in other organs. Thirty-one (6.4%) died due to disease recurrence. Size > 21 mm, G3 grade, nodal metastasis, and vascular infiltration were independent predictors of overall recurrence. Recurrence occurred either during the first year of follow-up (n = 9), or after 10 years (n = 4). CS analysis revealed that nonfunctioning G1 pan-NEN ≤20 mm without nodal metastasis or vascular invasion had a negligible risk of developing recurrence. In the present series, after 5 years of follow-up without developing recurrence, tumor recurrence occurred only in the form of liver metastases. CONCLUSIONS: Recurrence of pan-NENs is rare and is predicted by tumor size, nodal metastasis, grading, and vascular invasion. Patients with G1 pan-NEN without nodal metastasis and vascular invasion may be considered cured by surgery. After 5 years without recurrence, follow-up should focus on excluding the development of liver metastases.

Solid Pseudopapillary Neoplasms of the Pancreas: Clinicopathologic and Radiologic Features According to Size.

OBJECTIVE. The purpose of this study was to retrospectively analyze and correlate clinicopathologic and radiologic features of resected solid pseudopapillary neoplasms of the pancreas according to their size. MATERIALS AND METHODS. Clinicopathologic and radiologic features of 106 resected solid pseudopapillary neoplasms of the pancreas over a 20-year period were retrospectively analyzed. Tumors were divided into three groups according to their size (≤ 30 mm, 31-50 mm, and ≥ 51 mm). Clinicopathologic and radiologic features were compared among groups using Kruskal-Wallis and Fisher exact tests. RESULTS. Forty-one tumors that were 30 mm or smaller, 30 tumors between 31 and 50 mm, and 35 tumors that were 51 mm or larger were included. Preoperative MRI of 76 patients and CT of 40 patients were examined. Patients with tumors that were 30 mm or smaller were significantly older than the other groups of patients (p = 0.038). Large tumors (31-50 and ≥ 51 mm) were more frequently located in the pancreatic body or tail (p = 0.008). Most tumors had well-defined margins (87.7%) and a mixed solid and cystic appearance (54.7%) at imaging; tumors that were 30 mm or smaller were more frequently entirely solid (p = 0.028). At histologic analysis, 13 tumors had at least one feature of malignancy; nodal and liver metastases were found in one patient (0.9%). No significant differences between groups were found regarding the presence of malignant histologic features (p = 0.932). The rate of incorrect preoperative diagnosis was higher in tumors 30 mm or smaller, albeit without significant differences between groups (p = 0.561). CONCLUSION. Malignancy in solid pseudopapillary neoplasms is not correlated with tumor size; tumors that are 30 mm or smaller may present atypical imaging features, which may overlap those of other solid tumors of the pancreas.

The Actual Prevalence of Symptoms in Pancreatic Cystic Neoplasms: A Prospective Propensity Matched Cohort Analysis.

BACKGROUND: The prevalence of symptoms in pancreatic cystic neoplasms (PCNs) is mainly based on retrospective surgical series. The aim of this study is to describe the actual prevalence of symptoms in PCNs under surveillance. METHODS: Patients with PCNs under surveillance observed from 2015 to 2017 were submitted to magnetic resonance imaging (MRI) and a specific interview. An identical survey was carried out on a control population matched for age, sex, and comorbidities in which any pancreatic disease was excluded by MRI. RESULTS: Two groups of 184 individuals were compared. Patients with PCNs have a similar prevalence of abdominal pain when compared to controls (35.2 vs. 28.8, p = 0.2). PCNs in the distal pancreas experienced a significantly increased prevalence of abdominal pain (42.3 vs. 28.8%, p = 0.04), whereas size and presumed connection with the ductal system did not affect the prevalence of abdominal pain. PCNs associated with abdominal pain did not differ in terms of clinical and radiological features from asymptomatic ones. CONCLUSION: Patients with PCNs under surveillance have a similar prevalence of abdominal pain when compared to a matched population of controls. Abdominal pain might not correlate with radiological signs of malignancy.

Pancreatic Ultrasound: State of the Art.

An ultrasound (US) study is often the first imaging approach in patients with abdominal symptoms or signs related to abdominal diseases, and it is often part of the routine workup. The pancreatic gland, despite its retroperitoneal site, can be efficiently examined with US thanks to advances in US technologies. Nowadays, a pancreatic US study could be considered complete if multiparametric, including the use of Doppler imaging, US elastography, and contrast-enhanced imaging for the study of a pancreatic mass. A complete US examination could contribute to a faster diagnosis, especially if the pancreatic lesion is incidentally detected, addressing second-step imaging modalities correctly.

Activity-Based Cost Analysis of Including Contrast-Enhanced Ultrasound (CEUS) in the Diagnostic Pathway of Focal Pancreatic Lesions Detected by Abdominal Ultrasound.

PURPOSE: To perform an activity-based cost analysis of the inclusion of contrast-enhanced ultrasound (CEUS) in the diagnostic pathway of newly detected focal pancreatic lesions revealed by abdominal ultrasound (US) in comparison to computed tomography (CT) and magnetic resonance imaging (MRI). MATERIALS AND METHODS: Over a 14-year period, 977 patients with newly detected focal pancreatic lesions on US and subsequently studied with CEUS and/or CT and MRI were included. The cost of equipment, materials and human resources for every imaging method was calculated. We analyzed the costs in different scenarios considering whether or not CT or MRI was required in the diagnostic pathway. The savings (R) were calculated by subtracting the differential cost of CEUS from the eliminated third-level exam (CCEUS: CEUS cost; CCT: CT cost; CMRI: MRI cost) compared to conventional ultrasound (CCEUS-CUS): R = CCT-(CCEUS-CUS) or R = CMRI-(CCEUS-CUS). RESULTS: Total costs were: US 28.39 €; CEUS 70.50 €; CT 106.23 €; MRI 219.61 €. In 388/563 patients CEUS characterized the pancreatic lesion as solid, with only CT being performed as a second-level investigation: the savings were 68 870.36 €. In 266/414 patients CEUS diagnosed lesions as cystic, with only MRI being performed as a second-level examination: the savings were 16 825.07 €. Considering the whole diagnostic pathway of the patients, the cost savings were 76 809.35 € for solid lesions and 26 242.49 € for cystic lesions, with overall savings of 103 051.84 €. CONCLUSION: CEUS represents a cost-effective imaging method for the differentiation of focal pancreatic lesions and could guide the selection of the best imaging modality for preoperative assessment, thereby optimizing resources and securing the diagnostic pathway.