Special Issue "Developing Role of Diagnostic Imaging and Nuclear Medicine Applications in Pancreatic Tumors"

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Medical Imaging".

Deadline for manuscript submissions: closed (31 March 2021).

Special Issue Editors

Dr. Pierpaolo Alongi
E-Mail Website
Guest Editor
Fondazione Istituto G. Giglio, Italy
Interests: medical imaging; nuclear medicine; positron emission tomography; magnetic resonance; diagnostic imaging; computed tomography; diagnostic radiology; cancer research; oncology; neuroscience
Dr. Laura Evangelista
E-Mail Website
Guest Editor
Nuclear Medicine Unit, Department of Medicine, University of Padua, 35128 Padova, Italy
Interests: PET/CT; molecular imaging; radiopharmaceuticals; prostate cancer; PET/MRI
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Pancreatic neoplasm is a complex disease associated with a poor prognosis. Different histopathological types of pancreatic tumors have been reported, and the adenocarcinoma is the most common (more than 95%). At the time of diagnosis, patients often present in an advanced stage, since the disease is indolent and shows only non-specific symptoms like abdominal pain or weight loss. Therefore, an early and accurate diagnosis is of the utmost importance to determine the most effective therapy option and avoid futile surgery.

Pancreatic neuroendocrine tumors are rare, accounting for only 5% of all pancreatic tumors. However, their incidence is on the rise, most likely due to an improved awareness and incidental findings, as well as rapidly developing diagnostic methods.

Besides conventional imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI), molecular imaging with positron emission tomography (either PET/CT or PET/MRI) represents a powerful tool for detecting and evaluating pancreatic tumors in diverse disease settings. In this Special Issue we will contribute by collecting reviews or original data about theragnostic molecular imaging, in terms of both diagnosis (e.g., FDG, 68Ga-DOTA-peptides, and other radiopharmaceuticals for PET, 111In-Octeotride or similar tracers for SPECT, MRI and endoscopy) and therapy (e.g., 177Lu/90Y-DOTA-peptides).

Dr. Pierpaolo Alongi
Guest Editor

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Keywords

  • adenocarcinoma
  • neuroendocrine tumors
  • PET
  • MRI
  • CT
  • radionuclide therapy

Published Papers (9 papers)

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Research

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Article
Percutaneous Two-Dimensional Shear Wave Elastography for Diagnosis of Pancreatic Tumor
Diagnostics 2021, 11(3), 498; https://doi.org/10.3390/diagnostics11030498 - 11 Mar 2021
Cited by 1 | Viewed by 480
Abstract
Background: To investigate the efficacy of two-dimensional shear wave elastography (2D-SWE) for the diagnosis of pancreatic mass lesions. Methods: This ethics committee–approved cross-sectional study included 52 patients with histologically-proven pancreatic tumors (pancreatic ductal adenocarcinoma (PDAC), 36; tumor-forming pancreatitis (TFP), 15; neuroendocrine tumor, 1) [...] Read more.
Background: To investigate the efficacy of two-dimensional shear wave elastography (2D-SWE) for the diagnosis of pancreatic mass lesions. Methods: This ethics committee–approved cross-sectional study included 52 patients with histologically-proven pancreatic tumors (pancreatic ductal adenocarcinoma (PDAC), 36; tumor-forming pancreatitis (TFP), 15; neuroendocrine tumor, 1) and 33 control subjects. The 2D-SWE was performed for the tumor/non-tumor tissues, and SWE-mapping patterns and propagation quality were assessed. Results: Three mapping patterns were detected based on the size and distribution of the coloring areas. Pattern A (whole coloring) was detected in all non-tumor tissues and TFP, whereas pattern C (multiple small coloring spots) was detected in PDAC only. Pattern B (partial coloring with smaller spots) was detected in other lesions. The specificity and positive predictive value of pattern A for non-PDAC and those of pattern C for PDAC were 100%. The SWE value was higher in tumor lesions than in the non-tumor tissues (38.1 vs. 9.8 kPa; p < 0.001) in patients with PDAC. The SWE value in the non-tumor lesion was higher in patients with PDAC than in control (9.8 vs. 7.5 kPa; p < 0.001). Conclusions: 2D-SWE may play a role as a novel diagnostic tool for PDAC to detect a specific mapping pattern with quantitative assessment. Full article
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Article
Cost-Effectiveness Analysis of 68Ga DOTA-TATE PET/CT, 111In-Pentetreotide SPECT/CT and CT for Diagnostic Workup of Neuroendocrine Tumors
Diagnostics 2021, 11(2), 334; https://doi.org/10.3390/diagnostics11020334 - 18 Feb 2021
Cited by 2 | Viewed by 1009
Abstract
Neuroendocrine tumors (NETs) are relatively rare neoplasms arising from the hormone-producing neuroendocrine system that can occur in various organs such as pancreas, small bowel, stomach and lung. As the majority of these tumors express somatostatin receptors (SSR) on their cell membrane, utilization of [...] Read more.
Neuroendocrine tumors (NETs) are relatively rare neoplasms arising from the hormone-producing neuroendocrine system that can occur in various organs such as pancreas, small bowel, stomach and lung. As the majority of these tumors express somatostatin receptors (SSR) on their cell membrane, utilization of SSR analogs in nuclear medicine is a promising, but relatively costly approach for detection and localization. The aim of this study was to analyze the cost-effectiveness of 68Ga-DOTA-TATE PET/CT (Gallium-68 DOTA-TATE Positron emission tomography/computed tomography) compared to 111In-pentetreotide SPECT/CT (Indium-111 pentetreotide Single Photon emission computed tomography/computed tomography) and to CT (computed tomography) alone in detection of NETs. A decision model on the basis of Markov simulations evaluated lifetime costs and quality-adjusted life years (QALYs) related to either a CT, SPECT/CT or PET/CT. Model input parameters were obtained from publicized research projects. The analysis is grounded on the US healthcare system. Deterministic sensitivity analysis of diagnostic parameters and probabilistic sensitivity analysis predicated on a Monte Carlo simulation with 30,000 reiterations was executed. The willingness-to-pay (WTP) was determined to be $ 100,000/QALY. In the base-case investigation, PET/CT ended up with total costs of $88,003.07 with an efficacy of 4.179, whereas CT ended up with total costs of $88,894.71 with an efficacy of 4.165. SPECT/CT ended up with total costs of $89,973.34 with an efficacy of 4.158. Therefore, the strategies CT and SPECT/CT were dominated by PET/CT in the base-case scenario. In the sensitivity analyses, PET/CT remained a cost-effective strategy. This result was due to reduced therapy costs of timely detection. The additional costs of 68Ga-DOTA-TATE PET/CT when compared to CT alone are justified in the light of potential savings in therapy costs and better outcomes. Full article
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Article
Dual Tracer 68Ga-DOTATOC and 18F-FDG PET Improve Preoperative Evaluation of Aggressiveness in Resectable Pancreatic Neuroendocrine Neoplasms
Diagnostics 2021, 11(2), 192; https://doi.org/10.3390/diagnostics11020192 - 28 Jan 2021
Cited by 1 | Viewed by 806
Abstract
Purpose: To define an imaging risk profile in a population of patients affected by Pancreatic neuroendocrine neoplasms (PanNENs) candidates to surgery, by assessing the predictive role of 68Ga-DOTATOC and 18F-FDG PET/CT and PET/MR derived parameters in risk stratification, particularly regarding histological features of [...] Read more.
Purpose: To define an imaging risk profile in a population of patients affected by Pancreatic neuroendocrine neoplasms (PanNENs) candidates to surgery, by assessing the predictive role of 68Ga-DOTATOC and 18F-FDG PET/CT and PET/MR derived parameters in risk stratification, particularly regarding histological features of aggressive behaviour. Patients and methods: Retrospective study including 83 patients (53 males, 30 females; median age: 60 years, interquartile range 52–66.5), who underwent to 68Ga-DOTATOC (PET/CT: n = 77; PET/MR: n = 6) and, 68/83 patients, also to 18F-FDG PET (PET/CT: n = 65; PET/MR: n = 3) before surgery for PanNEN between 2011 and 2019, with available histological and follow-up data. The PET scans were interpreted with both qualitative (positive vs. negative) and semiquantitative measurements as follows: maximum and mean standardized uptake value (SUVmax and SUVmean) for both 18F-FDG and 68Ga-DOTATOC scans, metabolic tumour volume (MTV) and tumour lesion glycolysis (TLG) for 18F-FDG scans and somatostatin receptor density (SRD) and total lesion somatostatin receptor density (TLSRD) for 68Ga-DOTATOC PET. Receiver Operating Characteristics (ROC) curve analysis was used to investigate the performance of several PET parameters in predicting tumour stage or characteristic. For each PET parameter, the optimal cut-off was derived. Logistic regression analysis was used to assess if the PET parameters, categorized with the optimal cut-off values, were able to predict significantly the corresponding tumour stage or characteristic. Results: Overall, 29 (35%) patients had G1, 49 (59%) a G2 and five (6%) had a G3 PanNEN. The median Ki-67 index was 4% (interquartile range: 1–8%). SRD and TLSRD significantly discriminated between pT3 or pT4 PanNEN versus pT1 or pT2, as well as 18F-FDG MTV and TLG. 68Ga-DOTATOC SUVmax was able to significantly predict the presence of distant metastases with a threshold of 51.27 (sensitivity and specificity of 85.7 and 68.1%, respectively). 18F-FDG MTV and TLG were predictors of angioinvasion. The cut-off threshold for MTV was 7.98 (sensitivity and specificity of 69.7 and 82.4%, respectively) (p = 0.0004) whereas the cut-off for TLG was 32.4 (sensitivity and specificity of 69.7% and 82.4%, respectively) (p = 0.0004). Conclusion: Dual tracer 68Ga-DOTATOC and 18F-FDG PET scans provide relevant information regarding tumour behaviour and aggressiveness, implementing the diagnostic preoperative work-up. Full article
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Review

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Review
Focal Pancreatic Lesions: Role of Contrast-Enhanced Ultrasonography
Diagnostics 2021, 11(6), 957; https://doi.org/10.3390/diagnostics11060957 - 26 May 2021
Viewed by 979
Abstract
The introduction of contrast-enhanced ultrasonography (CEUS) has led to a significant improvement in the diagnostic accuracy of ultrasound in the characterization of a pancreatic mass. CEUS, by using a blood pool contrast agent, can provide dynamic information concerning macro- and micro-circulation of focal [...] Read more.
The introduction of contrast-enhanced ultrasonography (CEUS) has led to a significant improvement in the diagnostic accuracy of ultrasound in the characterization of a pancreatic mass. CEUS, by using a blood pool contrast agent, can provide dynamic information concerning macro- and micro-circulation of focal lesions and of normal parenchyma, without the use of ionizing radiation. On the basis of personal experience and literature data, the purpose of this article is to describe and discuss CEUS imaging findings of the main solid and cystic pancreatic lesions with varying prevalence. Full article
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Review
Role of PET/CT and Therapy Management of Pancreatic Neuroendocrine Tumors
Diagnostics 2020, 10(12), 1059; https://doi.org/10.3390/diagnostics10121059 - 07 Dec 2020
Cited by 6 | Viewed by 1397
Abstract
Pancreatic neuroendocrine neoplasms (panNENs) are heterogeneous neoplasms with neuroendocrine differentiation that show peculiar clinical and histomorphological features, with variable prognosis. In recent years, advances in knowledge regarding the pathophysiology and heterogeneous clinical presentation, as well as the availability of different diagnostic procedures for [...] Read more.
Pancreatic neuroendocrine neoplasms (panNENs) are heterogeneous neoplasms with neuroendocrine differentiation that show peculiar clinical and histomorphological features, with variable prognosis. In recent years, advances in knowledge regarding the pathophysiology and heterogeneous clinical presentation, as well as the availability of different diagnostic procedures for panNEN diagnosis and novel therapeutic options for patient clinical management, has led to the recognition of the need for an active multidisciplinary discussion for optimal patient care. Molecular imaging with positron emission tomography/computed tomography (PET/CT) has become indispensable for the management of panNENs. Several PET radiopharmaceuticals can be used to characterize either panNEN receptor expression or metabolism. The aim of this review is to offer an overview of all the currently used radiopharmaceuticals and of the new upcoming tracers for pancreatic neuroendocrine tumors (panNETs), and their clinical impact on therapy management. [68Ga]Ga-DOTA-peptide PET/CT (SSA-PET/CT) has high sensitivity, specificity, and accuracy and is recommended for the staging and restaging of any non-insulinoma well-differentiated panNEN cases to carry out detection of unknown primary tumor sites or early relapse and for evaluation of in vivo somatostatin receptors expression (SRE) to select patient candidates for peptide receptor radiometabolic treatment (PRRT) with 90Y or 177Lu and/or cold analogs. SSA-PET/CT also has a strong impact on clinical management, leading to a change in treatment in approximately a third of the cases. Its role for treatment response assessment is still under debate due to the lack of standardized criteria, even though some semiquantitative parameters seem to be able to predict response. [18F]FDG PET/CT generally shows low sensitivity in small growing and well-differentiated neuroendocrine tumors (NET; G1 and G2), while it is of utmost importance in the evaluation and management of high-grade NENs and also provides important prognostic information. When positive, [18F]FDG PET/CT impacts therapeutical management, indicating the need for a more aggressive treatment regime. Although FDG positivity does not exclude the patient from PRRT, several studies have demonstrated that it is certainly useful to predict response, even in this setting. The role of [18F]FDOPA for the study of panNET is limited by physiological uptake in the pancreas and is therefore not recommended. Moreover, it provides no information on SRE that has crucial clinical management relevance. Early acquisition of the abdomen and premedication with carbidopa may be useful to increase the accuracy, but further studies are needed to clarify its utility. GLP-1R agonists, such as exendin-4, are particularly useful for benign insulinoma detection, but their accuracy decreases in the case of malignant insulinomas. Being a whole-body imaging technique, exendin-PET/CT gives important preoperative information on tumor size and localization, which is fundamental for surgical planning as resection (enucleation of the lesion or partial pancreatic resection) is the only curative treatment. New upcoming tracers are under study, such as promising SSTR antagonists, which show a favorable biodistribution and higher tumor-to-background ratio that increases tumor detection, especially in the liver. [68Ga]pentixafor, an in vivo marker of CXCR4 expression associated with the behavior of more aggressive tumors, seems to only play a limited role in detecting well-differentiated NET since there is an inverse expression of SSTR2 and CXCR4 in G1 to G3 NETs with an elevation in CXCR4 and a decrease in SSTR2 expression with increasing grade. Other tracers, such as [68Ga]Ga-PSMA, [68Ga]Ga-DATA-TOC, [18F]SiTATE, and [18F]AlF-OC, are also under investigation. Full article
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Review
Clinical Impact of 18F-FDG PET/CT in the Diagnostic Workup of Pancreatic Ductal Adenocarcinoma: A Systematic Review
Diagnostics 2020, 10(12), 1042; https://doi.org/10.3390/diagnostics10121042 - 03 Dec 2020
Cited by 3 | Viewed by 1137
Abstract
In this review, the performance of fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in the diagnostic workup of pancreatic ductal adenocarcinoma (PDAC) is evaluated. A comprehensive literature search up to September 2020 was performed, selecting studies with the presence of: sample size ≥10 [...] Read more.
In this review, the performance of fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in the diagnostic workup of pancreatic ductal adenocarcinoma (PDAC) is evaluated. A comprehensive literature search up to September 2020 was performed, selecting studies with the presence of: sample size ≥10 patients and index test (i.e., “FDG” or “18F-FDG” AND “pancreatic adenocarcinoma” or “pancreas cancer” AND “PET” or “positron emission tomography”). The methodological quality was evaluated using the revised quality assessment of diagnostic accuracy studies (QUADAS-2) tool and presented according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Basic data (authors, year of publication, country and study design), patients’ characteristics (number of enrolled subjects and age), disease phase, type of treatment and grading were retrieved. Forty-six articles met the adopted research criteria. The articles were divided according to the considered clinical context. Namely, besides conventional anatomical imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI), molecular imaging with FDG PET/CT is an important tool in PDAC, for all disease stages. Further prospective studies will be necessary to confirm the cost-effectiveness of such imaging techniques by testing its real potential improvement in the clinical management of PDAC. Full article
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Review
Impact of F-18 Fluorodeoxyglucose PET/CT and PET/MRI on Initial Staging and Changes in Management of Pancreatic Ductal Adenocarcinoma: A Systemic Review and Meta-Analysis
Diagnostics 2020, 10(11), 952; https://doi.org/10.3390/diagnostics10110952 - 14 Nov 2020
Cited by 6 | Viewed by 718
Abstract
A systemic review and meta-analysis were conducted to investigate the diagnostic ability for staging and impact on management of F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and PET/magnetic resonance imaging (MRI) in patients with pancreatic ductal adenocarcinoma. A comprehensive search was performed [...] Read more.
A systemic review and meta-analysis were conducted to investigate the diagnostic ability for staging and impact on management of F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and PET/magnetic resonance imaging (MRI) in patients with pancreatic ductal adenocarcinoma. A comprehensive search was performed in four databases to retrieve studies of pancreatic ductal adenocarcinoma patients that have reported the diagnostic ability of FDG PET/CT and PET/MRI for detecting metastasis and the proportion of patients whose management was changed by its results. The sensitivity and specificity for detecting metastasis and the proportion of patients with management changes were pooled using a random-effects model. A total of 10 studies were included. The pooled sensitivity and specificity for detecting lymph node metastasis were 0.55 and 0.94, respectively, while the pooled sensitivity and specificity for detecting distant metastasis were 0.80 and 1.00, respectively. The areas under the summarized receiver operating characteristic curves for detecting lymph node and distant metastasis were 0.88 and 0.92, respectively. The pooled proportion of patients with management changes was 19%. FDG PET/CT and PET/MRI showed high diagnostic accuracy for detecting lymph node and distant metastasis in pancreatic ductal adenocarcinoma patients, and the use of these imaging tools led to management changes in a significant portion of these patients. Full article
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Review
Somatostatin Receptor PET/CT Imaging for the Detection and Staging of Pancreatic NET: A Systematic Review and Meta-Analysis
Diagnostics 2020, 10(8), 598; https://doi.org/10.3390/diagnostics10080598 - 16 Aug 2020
Cited by 11 | Viewed by 1917
Abstract
We investigated the diagnostic performance of Somatostatin Receptor Positron Emission Tomography/Computed Tomography (SSR-PET/CT) for the detection of primary lesion and initial staging of pancreatic neuroendocrine tumors (pNETs). A comprehensive literature search up to January 2020 was performed selecting studies in presence of: sample [...] Read more.
We investigated the diagnostic performance of Somatostatin Receptor Positron Emission Tomography/Computed Tomography (SSR-PET/CT) for the detection of primary lesion and initial staging of pancreatic neuroendocrine tumors (pNETs). A comprehensive literature search up to January 2020 was performed selecting studies in presence of: sample size ≥10 patients; index test (i.e., 68Ga-DOTATOC or 68Ga-DOTANOC or 68Ga-DOTATATE PET/CT); and outcomes (i.e., detection rate (DR), true positive, true negative, false positive, and false-negative). The methodological quality was evaluated with QUADAS-2. Pooled DR and pooled sensitivity and specificity for the identification of the primary tumor were assessed by a patient-based and a lesion-based analysis. Thirty-eight studies were selected for the qualitative analysis, while 18 papers were included in the meta-analysis. The number of pNET patients ranged from 10 to 142, for a total of 1143 subjects. At patient-based analysis, the pooled sensitivity and specificity for the assessment of primary pNET were 79.6% (95% confidence interval (95%CI): 71–87%) and 95% (95%CI: 75–100%) with a heterogeneity of 59.6% and 51.5%, respectively. Pooled DR for the primary lesion was 81% (95%CI: 65–90%) and 92% (95%CI: 80–97%), respectively, at patient-based and lesion-based analysis. In conclusion, SSR-PET/CT has high DR and diagnostic performances for primary lesion and initial staging of pNETs. Full article
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Other

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Interesting Images
Incidental Finding of a PSMA-Positive Pancreatic Cancer in a Patient Suffering from a Metastasized PSMA-Positive Prostate Cancer
Diagnostics 2021, 11(1), 129; https://doi.org/10.3390/diagnostics11010129 - 15 Jan 2021
Cited by 2 | Viewed by 561
Abstract
An 82-year-old man suffering from prostate cancer that was scheduled for a radioreceptor-ligand therapy (RLT) presented with jaundice to our service. An abdominal ultrasound (US) revealed obstructive extrahepatic cholestasis due to a solid lesion located in the uncinate process of the pancreas. The [...] Read more.
An 82-year-old man suffering from prostate cancer that was scheduled for a radioreceptor-ligand therapy (RLT) presented with jaundice to our service. An abdominal ultrasound (US) revealed obstructive extrahepatic cholestasis due to a solid lesion located in the uncinate process of the pancreas. The Prostate Specific Membrane Antigen (PSMA) PET/CT prior to RLT showed multilocular PSMA positive tumor lesions in the lymph nodes, the lung and the pancreas. On request of the cancer board, an Endoscopic Ultrasound (EUS)-guided Fine-Needle Aspiration (FNA) of the pancreatic mass was performed revealing invasive pancreatic ductal adenocarcinoma incompatible with a prostate cancer metastasis leading to the diagnosis of a PSMA positive pancreatic ductal adenocarcinoma. Full article
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