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Scalorbi F, Garanzini EM, Calareso G, Marzi C, Di Rocco G, Argiroffi G, Baccini M, Pusceddu S, Marchianò A, Maccauro M. Cylindrical TGR as early radiological predictor of RLT progression in GEPNETs: a proof of concept. Sci Rep 2024; 14:15782. [PMID: 38982134 PMCID: PMC11233714 DOI: 10.1038/s41598-024-66668-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 07/03/2024] [Indexed: 07/11/2024] Open
Abstract
This study aims to assess the predictive capability of cylindrical Tumor Growth Rate (cTGR) in the prediction of early progression of well-differentiated gastro-entero-pancreatic tumours after Radio Ligand Therapy (RLT), compared to the conventional TGR. Fifty-eight patients were included and three CT scans per patient were collected at baseline, during RLT, and follow-up. RLT response, evaluated at follow-up according to RECIST 1.1, was calculated as a percentage variation of lesion diameters over time (continuous values) and as four different RECIST classes. TGR between baseline and interim CT was computed using both conventional (approximating lesion volume to a sphere) and cylindrical (called cTGR, approximating lesion volume to an elliptical cylinder) formulations. Receiver Operating Characteristic (ROC) curves were employed for Progressive Disease class prediction, revealing that cTGR outperformed conventional TGR (area under the ROC equal to 1.00 and 0.92, respectively). Multivariate analysis confirmed the superiority of cTGR in predicting continuous RLT response, with a higher coefficient for cTGR (1.56) compared to the conventional one (1.45). This study serves as a proof of concept, paving the way for future clinical trials to incorporate cTGR as a valuable tool for assessing RLT response.
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Affiliation(s)
- Federica Scalorbi
- Nuclear Medicine Department, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy
| | - Enrico Matteo Garanzini
- Department of Radiodiagnostics and Radiotherapy, IRCCS Fondazione Istituto Nazionale Tumori, Milan, Italy
| | - Giuseppina Calareso
- Department of Radiodiagnostics and Radiotherapy, IRCCS Fondazione Istituto Nazionale Tumori, Milan, Italy
| | - Chiara Marzi
- Department of Statistics, Computer Science, Applications "G. Parenti", University of Florence, Viale Morgagni 59, 50134, Florence, Italy.
| | - Gabriella Di Rocco
- Department of Radiodiagnostics and Radiotherapy, IRCCS Fondazione Istituto Nazionale Tumori, Milan, Italy
- Post-Graduation School of Radiology, Department of Health Sciences, University of Milan, Milan, Italy
| | - Giovanni Argiroffi
- Nuclear Medicine Department, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy
| | - Michela Baccini
- Department of Statistics, Computer Science, Applications "G. Parenti", University of Florence, Viale Morgagni 59, 50134, Florence, Italy
| | - Sara Pusceddu
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Alfonso Marchianò
- Department of Radiodiagnostics and Radiotherapy, IRCCS Fondazione Istituto Nazionale Tumori, Milan, Italy
| | - Marco Maccauro
- Nuclear Medicine Department, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy
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Notake T, Shimizu A, Kubota K, Sugenoya S, Umemura K, Goto T, Yamada A, Fujinaga Y, Soejima Y. Usefulness of intratumoral perfusion analysis for assessing biological features of non-functional pancreatic neuroendocrine neoplasm. Langenbecks Arch Surg 2024; 409:38. [PMID: 38221590 DOI: 10.1007/s00423-023-03219-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 12/29/2023] [Indexed: 01/16/2024]
Abstract
PURPOSE Here, we evaluated the usefulness of intratumoral perfusion analysis using preoperative contrast-enhanced CT (E-CT) to assess biological features of non-functional pancreatic neuroendocrine neoplasms (NF-PanNENs). METHODS We retrospectively studied 44 patients who underwent curative surgery for NF-PanNENs. We used preoperative E-CT with compartment model analysis to calculate the tumor perfusion parameters K1 (inflow rate constant), 1/k2 (mean transit time), and K1/k2 (distribution volume). We assessed the association between perfusion parameters and biological features of NF-PanNENs, including the WHO classification tumor histopathological grade and prognosis after surgery. RESULTS Patients in this study had a neuroendocrine tumor (NET) G1 (n = 32) or NET G2 (n = 12). Neither NET G3 or NEC tumors were observed. Among perfusion parameters, K1 was the most accurate predictor of the high-grade tumor (AUC: 0.726). K1-low (< 0.028 s-1) was significantly associated with large tumors (≥ 20 mm) (p = 0.022), high mitotic index (p = 0.017), high Ki-67 index (p = 0.004), and lymphatic invasion (p = 0.025). Synchronous extra-pancreatic metastasis, including lymph node metastasis or liver metastasis, more frequently developed in K1-low patients than in K1-high patients (29% vs 4%, p = 0.025). Disease-free survival of patients with a K1-low tumor was poorer than that of patients with a K1-high tumor (p = 0.005). Furthermore, no patient with a K1-high tumor developed recurrence after initial surgery. CONCLUSION The perfusion parameters obtained using E-CT were significantly associated with biological features and prognosis of NF-PanNENs.
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Affiliation(s)
- Tsuyoshi Notake
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan.
| | - Akira Shimizu
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan
| | - Koji Kubota
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan
| | - Shinsuke Sugenoya
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan
| | - Kentaro Umemura
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan
| | - Takamune Goto
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan
| | - Akira Yamada
- Department of Radiology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Yasunari Fujinaga
- Department of Radiology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Yuji Soejima
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan
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Dicitore A, Gaudenzi G, Carra S, Cantone MC, Oldani M, Saronni D, Borghi MO, Grotteschi J, Persani L, Vitale G. Antitumor Activity of Axitinib in Lung Carcinoids: A Preclinical Study. Cancers (Basel) 2023; 15:5375. [PMID: 38001635 PMCID: PMC10669991 DOI: 10.3390/cancers15225375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 10/22/2023] [Accepted: 11/09/2023] [Indexed: 11/26/2023] Open
Abstract
Lung carcinoids (LCs) comprise well-differentiated neuroendocrine tumors classified as typical (TCs) and atypical (ACs) carcinoids. Unfortunately, curative therapies remain elusive for metastatic LCs, which account for 25-30% of cases. This study evaluated the antitumor activity of axitinib (AXI), a second-generation tyrosine kinase inhibitor selectively targeting vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, VEGFR-3) in human lung TC (NCI-H727, UMC-11, NCI-H835) and AC (NCI-H720) cell lines. In vitro and in vivo (zebrafish) assays were performed following AXI treatment to gather several read-outs about cell viability, cell cycle, the secretion of proangiogenic factors, apoptosis, tumor-induced angiogenesis and migration. AXI demonstrated relevant antitumor activity in human LC cells, with pronounced effects observed in UMC-11 and NCI-H720, characterized by cell cycle perturbation and apoptosis induction. AXI significantly hindered tumor induced-angiogenesis in Tg(fli1a:EGFP)y1 zebrafish embryos implanted with all LC cell lines and also reduced the invasiveness of NCI-H720 cells, as well as the secretion of several proangiogenic factors. In conclusion, our study provides initial evidence supporting the potential anti-tumor activity of AXI in LC, offering a promising basis for future investigations in mammalian animal models and, eventually, progressing to clinical trials.
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Affiliation(s)
- Alessandra Dicitore
- Department of Medical Biotechnology and Translational Medicine, University of Milan, 20122 Milan, Italy; (A.D.); (D.S.); (J.G.); (L.P.)
| | - Germano Gaudenzi
- Laboratory of Geriatric and Oncologic Neuroendocrinology Research, IRCCS, Istituto Auxologico Italiano, 20145 Milan, Italy; (G.G.); (M.C.C.); (M.O.)
| | - Silvia Carra
- Laboratory of Endocrine and Metabolic Research, IRCCS, Istituto Auxologico Italiano, 20145 Milan, Italy;
| | - Maria Celeste Cantone
- Laboratory of Geriatric and Oncologic Neuroendocrinology Research, IRCCS, Istituto Auxologico Italiano, 20145 Milan, Italy; (G.G.); (M.C.C.); (M.O.)
| | - Monica Oldani
- Laboratory of Geriatric and Oncologic Neuroendocrinology Research, IRCCS, Istituto Auxologico Italiano, 20145 Milan, Italy; (G.G.); (M.C.C.); (M.O.)
| | - Davide Saronni
- Department of Medical Biotechnology and Translational Medicine, University of Milan, 20122 Milan, Italy; (A.D.); (D.S.); (J.G.); (L.P.)
| | - Maria Orietta Borghi
- Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy;
- Experimental Laboratory of Immuno-Rheumatology, IRCCS, Istituto Auxologico Italiano, 20145 Milan, Italy
| | - Jacopo Grotteschi
- Department of Medical Biotechnology and Translational Medicine, University of Milan, 20122 Milan, Italy; (A.D.); (D.S.); (J.G.); (L.P.)
| | - Luca Persani
- Department of Medical Biotechnology and Translational Medicine, University of Milan, 20122 Milan, Italy; (A.D.); (D.S.); (J.G.); (L.P.)
- Laboratory of Endocrine and Metabolic Research, IRCCS, Istituto Auxologico Italiano, 20145 Milan, Italy;
| | - Giovanni Vitale
- Department of Medical Biotechnology and Translational Medicine, University of Milan, 20122 Milan, Italy; (A.D.); (D.S.); (J.G.); (L.P.)
- Laboratory of Geriatric and Oncologic Neuroendocrinology Research, IRCCS, Istituto Auxologico Italiano, 20145 Milan, Italy; (G.G.); (M.C.C.); (M.O.)
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Ligero M, Hernando J, Delgado E, Garcia-Ruiz A, Merino-Casabiel X, Ibrahim T, Fazio N, Lopez C, Teulé A, Valle JW, Tafuto S, Custodio A, Reed N, Raderer M, Grande E, Garcia-Carbonero R, Jimenez-Fonseca P, Garcia-Alvarez A, Escobar M, Casanovas O, Capdevila J, Perez-Lopez R. Radiomics and outcome prediction to antiangiogenic treatment in advanced gastroenteropancreatic neuroendocrine tumours: findings from the phase II TALENT trial. BJC REPORTS 2023; 1:9. [PMID: 39516643 PMCID: PMC11523983 DOI: 10.1038/s44276-023-00010-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 07/06/2023] [Accepted: 07/10/2023] [Indexed: 11/16/2024]
Abstract
BACKGROUND More accurate predictive biomarkers in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are needed. This study aims to investigate radiomics-based tumour phenotypes as a surrogate biomarker of the tumour vasculature and response prediction to antiangiogenic targeted agents in patients with GEP-NETs. METHODS In this retrospective study, a radiomics signature was developed in patients with GEP-NETs and liver metastases receiving lenvatinib. Patients were selected from the multicentre phase II TALENT trial (NCT02678780) (development cohort). Radiomics variables were extracted from liver metastases in the pre-treatment CT-scans and selected using LASSO regression and minimum redundancy maximum relevance (mRMR). Logistic regression and Cox proportional-hazards models for radiomics and combined radiomics with clinical data were explored. The performance of the models was tested in an external cohort of patients treated with sunitinib (test cohort). Associations between the radiomics score and vascularisation factors in plasma were studied using hierarchical clustering and Mann-Whitney U test. RESULTS A total of 89 patients were included in the study, 408 liver metastases were analysed. The CT-based radiomics signature was associated with clinical benefit in the development (training and validation sets) and test cohorts (AUC 0.75 [0.66-0.90], 0.67 [0.49-0.92] and 0.67 [0.43-0.91], respectively). The combined radiomics-clinical signature (including the radiomics score, Ki-67 index and primary tumour site) improved on radiomics-only signature performance (AUC 0.79 [95% CI 0.64-0.93]; p < 0.001). A higher radiomics score indicated longer progression-free survival (hazard ration of 0.11 [0.03-0.45]; p = 0.002) and was associated with vascularisation factors (p = 0.01). CONCLUSIONS Radiomics-based phenotypes can provide valuable information about tumour characteristics, including the vasculature, that are associated with response to antiangiogenics. CLINICAL TRIAL REGISTRATION This is a study of the Lenvatinib Efficacy in Metastatic Neuroendocrine Tumours (TALENT) phase II clinical trial (NCT02678780).
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Affiliation(s)
- Marta Ligero
- Radiomics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
| | - Jorge Hernando
- Oncology Department, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
| | - Eric Delgado
- Radiomics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
| | - Alonso Garcia-Ruiz
- Radiomics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
| | | | - Toni Ibrahim
- Osteoncology and Rare Tumours Centre, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Meldola, Italy
| | - Nicola Fazio
- Units of Gastrointestinal and Neuroendocrine Tumours, European Institute of Oncology, Milan, Italy
| | - Carlos Lopez
- Oncology Department, Marques de Valdecilla University Hospital (IDIVAL), Santander, Spain
| | - Alexandre Teulé
- Oncology Department, Catalan Institute of Oncology (ICO), L'Hospitalet de Llobregat (Barcelona), Spain
| | - Juan W Valle
- University of Manchester and The Christie NHS Foundation Trust, Manchester, UK
| | - Salvatore Tafuto
- S.C. Sarcomi e Tumori Rari, Istituto Nazionale Tumori, IRCCS, Fondazione "G. Pascale", Naples, Italy
| | - Ana Custodio
- Oncology Department, La Paz University Hospital, Madrid, Spain
| | - Nicholas Reed
- Gartnavel Hospital, Beatson Oncology Centre, Glasgow, UK
| | - Markus Raderer
- Department of Oncology and Internal Medicine, Medical University of Vienna, Vienna, Austria
| | - Enrique Grande
- Oncology Department, MD Anderson Cancer Center, Madrid, Spain
| | | | | | | | - Manuel Escobar
- Radiology Department, Vall d'Hebron University Hospital (VHUH), Barcelona, Spain
| | - Oriol Casanovas
- Oncology Department, Catalan Institute of Oncology (ICO), L'Hospitalet de Llobregat (Barcelona), Spain
| | - Jaume Capdevila
- Oncology Department, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
| | - Raquel Perez-Lopez
- Radiomics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
- Radiology Department, Vall d'Hebron University Hospital (VHUH), Barcelona, Spain.
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Prognostic value of tumor-to-parenchymal contrast enhancement ratio on portal venous-phase CT in pancreatic neuroendocrine neoplasms. Eur Radiol 2023; 33:2713-2724. [PMID: 36378252 DOI: 10.1007/s00330-022-09235-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 10/07/2022] [Accepted: 10/12/2022] [Indexed: 11/16/2022]
Abstract
OBJECTIVES We aimed to evaluate the prognostic value of tumor-to-parenchymal contrast enhancement ratio on portal venous-phase CT (CER on PVP) and compare its prognostic performance to prevailing grading and staging systems in pancreatic neuroendocrine neoplasms (PanNENs). METHODS In this retrospective study, data on 465 patients (development cohort) who underwent upfront curative-intent resection for PanNEN were used to assess the performance of CER on PVP and tumor size measured by CT (CT-Size) in predicting recurrence-free survival (RFS) using Harrell's C-index and to determine their optimal cutoffs to stratify RFS using a multi-way partitioning algorithm. External data on 184 patients (test cohort) were used to validate the performance of CER on PVP in predicting RFS and overall survival (OS) and compare its predictive performance with those of CT-Size, 2019 World Health Organization classification system (WHO), and the 8th American Joint Committee on Cancer staging system (AJCC). RESULTS In the test cohort, CER on PVP showed C-indexes of 0.83 (95% confidence interval [CI], 0.74-0.91) and 0.84 (95% CI, 0.73-0.95) for predicting RFS and OS, respectively, which were higher than those for the WHO (C-index: 0.73 for RFS [p = .002] and 0.72 for OS [p = .004]) and AJCC (C-index, 0.67 for RFS [p = .002] and 0.58 for OS [p = .002]). CT-Size obtained C-indexes of 0.71 for RFS and 0.61 for OS. CONCLUSIONS CER on PVP showed superior predictive performance on postoperative survival in PanNEN than current grading and staging systems, indicating its potential as a noninvasive preoperative prognostic tool. KEY POINTS • In pancreatic neuroendocrine neoplasms, the tumor-to-parenchymal enhancement ratio on portal venous-phase CT (CER on PVP) showed acceptable predictive performance of postoperative outcomes. • CER on PVP showed superior predictive performance of postoperative survival over the current WHO classification and AJCC staging system.
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Neuroendocrine Tumor Therapy Response Assessment. PET Clin 2023; 18:267-286. [PMID: 36858748 DOI: 10.1016/j.cpet.2022.11.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/03/2023]
Abstract
Peptide receptor radionuclide therapy has become an integral part of management of neuroendocrine neoplasms. Gallium-68- and lutetium-177-labeled somatostatin receptor analogues have replaced yttrium-90- and 111-indium-based tracers. Several newer targeted therapies are also being used in clinical and research settings. It is imperative to accurately evaluate the response to these agents. The characteristics of NENs and the response patterns of the targeted therapies make response assessment in this group challenging. This article provides an overview of the strengths and weaknesses of the various biomarkers available for response assessment.
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7
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Makris EA, Cannon JGD, Norton JA, Lopez-Aguiar AG, Dillhoff M, Beal E, Idrees K, Smith PM, Rocha FG, Kanji Z, Cho C, Beems M, Weber S, Fisher A, Krasnick BA, Fields RC, Maithel SK, Poultsides GA. Calcifications and Cystic Morphology on Preoperative Imaging Predict Survival After Resection of Pancreatic Neuroendocrine Tumors. Ann Surg Oncol 2023; 30:2424-2430. [PMID: 36434481 DOI: 10.1245/s10434-022-12783-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 10/24/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND Radiographic calcifications and cystic morphology are associated with higher and lower tumor grade, respectively, in pancreatic neuroendocrine tumors (PNETs). Whether calcifications and/or cystic morphology could be used preoperatively to predict post-resection survival in patients with PNETs remains elusive. METHODS Patients undergoing curative-intent resection of well-differentiated PNETs from 2000 to 2017 at eight academic institutions participating in the US Neuroendocrine Tumor Study Group were identified. Preoperative cross-sectional imaging reports were reviewed to identify the presence of calcifications and of a cystic component occupying >50% of the total tumor area. Clinicopathologic characteristics and recurrence-free survival (RFS) were compared. RESULTS Of 981 patients studied, 18% had calcifications and 17% had cystic tumors. Tumors with calcifications were more commonly associated with Ki-67 ≥3% (47% vs. 33%; p = 0.029), lymph node metastasis (36% vs. 24%; p = 0.011), and distant metastasis (13% vs. 4%; p < 0.001). In contrast, cystic tumors were less commonly associated with lymph node metastasis (12% vs. 30%; p < 0.001). Five-year RFS after resection was most favorable for cystic tumors without calcifications (91%), intermediate for solid tumors without calcifications (77%), and least favorable for any calcified PNET (solid 69%, cystic 67%; p = 0.043). Calcifications remained an independent predictor of RFS on multivariable analysis (p = 0.043) controlling for nodal (p < 0.001) and distant metastasis (p = 0.001). CONCLUSIONS Easily detectable radiographic features, such as calcifications and cystic morphology, can be used preoperatively to stratify prognosis in patients with PNETs and possibly inform the decision to operate or not, as well as guide the extent of resection and potential use of neoadjuvant therapy.
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Affiliation(s)
- Eleftherios A Makris
- Section of Surgical Oncology, Division of General Surgery, Department of Surgery, Stanford University, Stanford, CA, USA
| | - John G Douglas Cannon
- Section of Surgical Oncology, Division of General Surgery, Department of Surgery, Stanford University, Stanford, CA, USA
| | - Jeffrey A Norton
- Section of Surgical Oncology, Division of General Surgery, Department of Surgery, Stanford University, Stanford, CA, USA
| | | | - Mary Dillhoff
- Department of Surgery, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - Eliza Beal
- Department of Surgery, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - Kamran Idrees
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | | | - Flavio G Rocha
- Department of Surgery, Virginia Mason Medical Center, Seattle, WA, USA
| | - Zaheer Kanji
- Department of Surgery, Virginia Mason Medical Center, Seattle, WA, USA
| | - Clifford Cho
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Megan Beems
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Sharon Weber
- Department of Surgery, University of Wisconsin, Madison, WI, USA
| | - Alexander Fisher
- Department of Surgery, University of Wisconsin, Madison, WI, USA
| | | | - Ryan C Fields
- Department of Surgery, Washington University, St Louis, MO, USA
| | | | - George A Poultsides
- Section of Surgical Oncology, Division of General Surgery, Department of Surgery, Stanford University, Stanford, CA, USA.
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Marcal LP, Chuang HH, Tran Cao HS, Halperin DM. Pancreatic Neuroendocrine Tumors. ONCOLOGIC IMAGING : A MULTIDISCIPLINARY APPROACH 2023:197-217. [DOI: 10.1016/b978-0-323-69538-1.00014-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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9
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Galgano SJ, Morani AC, Gopireddy DR, Sharbidre K, Bates DDB, Goenka AH, Arif-Tiwari H, Itani M, Iravani A, Javadi S, Faria S, Lall C, Bergsland E, Verma S, Francis IR, Halperin DM, Chatterjee D, Bhosale P, Yano M. Pancreatic neuroendocrine neoplasms: a 2022 update for radiologists. ABDOMINAL RADIOLOGY (NEW YORK) 2022; 47:3962-3970. [PMID: 35244755 DOI: 10.1007/s00261-022-03466-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 02/17/2022] [Accepted: 02/18/2022] [Indexed: 01/18/2023]
Abstract
Pancreatic neuroendocrine neoplasms (PaNENs) are a unique group of pancreatic neoplasms with a wide range of clinical presentations and behaviors. Given their heterogeneous appearance and increasing detection on cross-sectional imaging, it is essential that radiologists understand the variable presentation and distinctions PaNENs display compared to other pancreatic neoplasms. Additionally, some of these neoplasms may be hormonally functional, and it is imperative that radiologists be aware of the common clinical presentations of hormonally active PaNENs. Knowledge of PaNEN pathology and treatments may influence which imaging modality is optimal for each patient. Each imaging modality used for PaNENs has distinct advantages and disadvantages, particularly in different treatment settings. Thus, the focus of this manuscript is to provide an update for the radiologist on PaNEN pathology, imaging, and treatments.
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Affiliation(s)
- Samuel J Galgano
- Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA.
| | | | - Dheeraj R Gopireddy
- Department of Radiology, University of Florida-Jacksonville, Jacksonville, FL, USA
| | - Kedar Sharbidre
- Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - David D B Bates
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Ajit H Goenka
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | - Hina Arif-Tiwari
- Department of Radiology, University of Arizona-Tuscon, Tuscon, AZ, USA
| | - Malak Itani
- Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, USA
| | - Amir Iravani
- Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, USA
| | - Sanaz Javadi
- Department of Radiology, M.D. Anderson Cancer Center, Houston, TX, USA
| | - Silvana Faria
- Department of Radiology, M.D. Anderson Cancer Center, Houston, TX, USA
| | - Chandana Lall
- Department of Radiology, University of Florida-Jacksonville, Jacksonville, FL, USA
| | - Emily Bergsland
- Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Sadhna Verma
- Department of Radiology, University of Cincinnati, Cincinnati, OH, USA
| | - Isaac R Francis
- Department of Radiology, Michigan Medicine, Ann Arbor, MI, USA
| | - Daniel M Halperin
- Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, Houston, TX, USA
| | - Deyali Chatterjee
- Department of Pathology, M.D. Anderson Cancer Center, Houston, TX, USA
| | - Priya Bhosale
- Department of Radiology, M.D. Anderson Cancer Center, Houston, TX, USA
| | - Motoyo Yano
- Department of Radiology, Mayo Clinic Arizona, Scottsdale, AZ, USA
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Qualitative imaging features of pancreatic neuroendocrine neoplasms predict histopathologic characteristics including tumor grade and patient outcome. ABDOMINAL RADIOLOGY (NEW YORK) 2022; 47:3971-3985. [PMID: 35166939 DOI: 10.1007/s00261-022-03430-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 01/22/2022] [Accepted: 01/25/2022] [Indexed: 01/18/2023]
Abstract
OBJECTIVES To identify PanNEN imaging features associated with tumor grade and aggressive histopathological features. METHODS Associations between histopathological and imaging features of resected PanNEN were retrospectively tested. Histopathologic features included WHO grade, lymphovascular invasion (LVI), growth pattern (infiltrative, circumscribed), and intratumoral fibrosis (mature, immature). Imaging features included size, degree/uniformity of enhancement, progressive enhancement, contour, infiltrative appearance (infiltrativeim), calcifications, cystic components, tumor thrombus, vascular occlusion (VO), duct dilatation, and atrophy. Multinomial logistic regression analyses evaluated the magnitude of associations. Association of variables with outcome was assessed using Cox-proportional hazards regression. RESULTS 133 patients were included. 3 imaging features (infiltrativeim, ill-defined contour [contourill], and VO) were associated with all histopathologic parameters and poor outcome. Increase in grade increased odds of contourill by 15.6 times (p = 0.0001, 95% CI 3.8-64.4). PanNEN with VO were 51.1 times (p = 0.0002, 6.5-398.6) more likely to demonstrate LVI. For PanNEN with contourill, infiltrative growth pattern was 51.3 times (p < 0.0001, 9.1-288.4), and fibrosis was 14 times (p = 0.0065, 2.1-93.7) more likely. Contourill was associated with decreased recurrence-free survival (p = 0.0003, HR 18.29, 3.83-87.3) and VO (p = 0.0004, HR6.08, 2.22-16.68) with decreased overall survival. CONCLUSIONS Infiltrativeim, contourill, and VO on imaging are associated with higher grade/histopathological parameters linked to tumor aggression, and poor outcome.
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Chen H, Li Z, Hu Y, Xu X, Ye Z, Lou X, Zhang W, Gao H, Qin Y, Zhang Y, Chen X, Chen J, Tang W, Yu X, Ji S. Maximum Value on Arterial Phase Computed Tomography Predicts Prognosis and Treatment Efficacy of Sunitinib for Pancreatic Neuroendocrine Tumours. Ann Surg Oncol 2022; 30:2988-2998. [PMID: 36310316 DOI: 10.1245/s10434-022-12693-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 10/06/2022] [Indexed: 12/15/2022]
Abstract
PURPOSE This study was designed to assess the computed tomography maximum (CTmax) value on pretherapeutic arterial phase computed tomography (APCT) images to predict pancreatic neuroendocrine tumours (pNETs) recurrence and clarify its role in predicting the outcome of tumour therapy. METHODS This retrospective study enrolled 250 surgical patients and 24 nonsurgical patients with sunitinib-based treatment in our hospital from 2008 to 2019. CT images were assessed, the maximum value was defined as "CTmax," and recurrence-free survival (RFS) or progression-free survival (PFS) was compared between a high-CTmax group and a low-CTmax group among patients who underwent surgical resection or nonsurgical, sunitinib-based treatment according to the CTmax cutoff value. RESULTS In ROC curve analysis, a CTmax of 108 Hounsfield units, as the cutoff value, achieved an AUC of 0.796 in predicting recurrence. Compared with the low-CTmax group, the high-CTmax group had a longer RFS (p < 0.001). Low CTmax was identified as an independent factor for RFS (p < 0.001) in multivariate analysis; these results were confirmed using the internal validation set. The CTmax value was significantly correlated with the microvascular density (MVD) value (p < 0.001) and the vascular endothelial growth factor receptor 2 (VEGFR2) score (p < 0.001). Furthermore, the high-CTmax group had a better PFS than the low-CTmax group among the sunitinib treatment group (p = 0.007). CONCLUSIONS The tumour CTmax on APCT might be a potential and independent indicator for predicting recurrence in patients who have undergone surgical resection and assessing the efficacy of sunitinib for patients with advanced metastatic pNETs.
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Affiliation(s)
- Haidi Chen
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Zheng Li
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Yuheng Hu
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Xiaowu Xu
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Zeng Ye
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Xin Lou
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Wuhu Zhang
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Heli Gao
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Yi Qin
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Yue Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The Third Affiliated Hospital of Suzhou University, The First People's Hospital of Changzhou, Changzhou, China
| | - Xuemin Chen
- Department of Hepatobiliary and Pancreatic Surgery, The Third Affiliated Hospital of Suzhou University, The First People's Hospital of Changzhou, Changzhou, China
| | - Jie Chen
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Wei Tang
- Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
| | - Xianjun Yu
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China.
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
- Shanghai Pancreatic Cancer Institute, Shanghai, China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, China.
| | - Shunrong Ji
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, China.
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
- Shanghai Pancreatic Cancer Institute, Shanghai, China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, China.
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Circulating Angiogenic Markers in Gastroenteropancreatic Neuroendocrine Neoplasms: A Systematic Review. Curr Issues Mol Biol 2022; 44:4001-4014. [PMID: 36135186 PMCID: PMC9497497 DOI: 10.3390/cimb44090274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 08/26/2022] [Accepted: 08/30/2022] [Indexed: 11/30/2022] Open
Abstract
Background: Neuroendocrine neoplasms are a heterogeneous group of tumors that raise challenges in terms of diagnosis, treatment and monitoring. Despite continuous efforts, no biomarker has showed satisfying accuracy in predicting outcome or response to treatment. Methods: We conducted a systematic review to determine relevant circulating biomarkers for angiogenesis in neuroendocrine tumors. We searched three databases (Pubmed, Embase, Web of Science) using the keywords “neuroendocrine” and “biomarkers”, plus specific biomarkers were searched by full and abbreviated name. From a total of 2448 publications, 11 articles met the eligibility criteria. Results: VEGF is the most potent and the most studied angiogenic molecule, but results were highly controversial. Placental growth factor, Angiopoietin 2 and IL-8 were the most consistent markers in predicting poor outcome and aggressive disease behavior. Conclusions: There is no robust evidence so far to sustain the use of angiogenic biomarkers in routine practice, although the results show promising leads.
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Saleh M, Bhosale PR, Yano M, Itani M, Elsayes AK, Halperin D, Bergsland EK, Morani AC. New frontiers in imaging including radiomics updates for pancreatic neuroendocrine neoplasms. Abdom Radiol (NY) 2022; 47:3078-3100. [PMID: 33095312 DOI: 10.1007/s00261-020-02833-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 10/07/2020] [Accepted: 10/12/2020] [Indexed: 01/18/2023]
Abstract
OBJECTIVE To illustrate the applications of various imaging tools including conventional MDCT, MRI including DWI, CT & MRI radiomics, FDG & DOTATATE PET-CT for diagnosis, staging, grading, prognostication, treatment planning and assessing treatment response in cases of pancreatic neuroendocrine neoplasms (PNENs). BACKGROUND Gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) are very diverse clinically & biologically. Their treatment and prognosis depend on staging and primary site, as well as histological grading, the importance of which is also reflected in the recently updated WHO classification of GEP NENs. Grade 3 poorly differentiated neuroendocrine carcinomas (NECs) are aggressive & nearly always advanced at diagnosis with poor prognosis; whereas Grades-1 and 2 well-differentiated neuroendocrine tumors (NETs) can be quite indolent. Grade 3 well-differentiated NETs represent a new category of neoplasm with an intermediate prognosis. Importantly, the evidence suggest grade heterogeneity can occur within a given tumor and even grade progression can occur over time. Emerging evidence suggests that several non-invasive qualitative and quantitative imaging features on CT, dual-energy CT (DECT), MRI, PET and somatostatin receptor imaging with new tracers, as well as texture analysis, may be useful to grade, prognosticate, and accurately stage primary NENs. Imaging features may also help to inform choice of treatment and follow these neoplasms post-treatment. CONCLUSION GEP NENs treatment and prognosis depend on the stage as well as histological grade of the tumor. Traditional ways of imaging evaluation for diagnosis and staging does not yet yield sufficient information to replace operative and histological evaluation. Recognition of important qualitative imaging features together with quantitative features and advanced imaging tools including functional imaging with DWI MRI, DOTATATE PET/CT, texture analysis with radiomics and radiogenomic features appear promising for more accurate staging, tumor risk stratification, guiding management and assessing treatment response.
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Affiliation(s)
- Mohammed Saleh
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holocombe Blvd, Houston, TX, 77030, USA
| | - Priya R Bhosale
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holocombe Blvd, Houston, TX, 77030, USA
| | - Motoyo Yano
- Department of Radiology, Mayo Clinic Hospital, Phoenix, AZ, 77030, USA
| | - Malak Itani
- Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
| | - Ahmed K Elsayes
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holocombe Blvd, Houston, TX, 77030, USA
| | - Daniel Halperin
- GI Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holocombe Blvd, Houston, TX, 77030, USA
| | - Emily K Bergsland
- University of California San Francisco, San Francisco, CA, 94143, USA
| | - Ajaykumar C Morani
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holocombe Blvd, Houston, TX, 77030, USA.
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Aberrant transcription factors in the cancers of the pancreas. Semin Cancer Biol 2022; 86:28-45. [PMID: 36058426 DOI: 10.1016/j.semcancer.2022.08.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 08/15/2022] [Accepted: 08/29/2022] [Indexed: 11/21/2022]
Abstract
Transcription factors (TFs) are essential for proper activation of gene set during the process of organogenesis, differentiation, lineage specificity. Reactivation or dysregulation of TFs regulatory networks could lead to deformation of organs, diseases including various malignancies. Currently, understanding the mechanism of oncogenesis became necessity for the development of targeted therapeutic strategy for different cancer types. It is evident that many TFs go awry in cancers of the pancreas such as pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine neoplasms (PanNENs). These mutated or dysregulated TFs abnormally controls various signaling pathways in PDAC and PanNENs including RTK, PI3K-PTEN-AKT-mTOR, JNK, TGF-β/SMAD, WNT/β-catenin, SHH, NOTCH and VEGF which in turn regulate different hallmarks of cancer. Aberrant regulation of such pathways have been linked to the initiation, progression, metastasis, and resistance in pancreatic cancer. As of today, a number of TFs has been identified as crucial regulators of pancreatic cancer and a handful of them shown to have potential as therapeutic targets in pre-clinical and clinical settings. In this review, we have summarized the current knowledge on the role and therapeutic usefulness of TFs in PDAC and PanNENs.
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Carra S, Gaudenzi G, Dicitore A, Cantone MC, Plebani A, Saronni D, Zappavigna S, Caraglia M, Candeo A, Bassi A, Persani L, Vitale G. Modeling Lung Carcinoids with Zebrafish Tumor Xenograft. Int J Mol Sci 2022; 23:8126. [PMID: 35897702 PMCID: PMC9330857 DOI: 10.3390/ijms23158126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Revised: 07/19/2022] [Accepted: 07/20/2022] [Indexed: 02/01/2023] Open
Abstract
Lung carcinoids are neuroendocrine tumors that comprise well-differentiated typical (TCs) and atypical carcinoids (ACs). Preclinical models are indispensable for cancer drug screening since current therapies for advanced carcinoids are not curative. We aimed to develop a novel in vivo model of lung carcinoids based on the xenograft of lung TC (NCI-H835, UMC-11, and NCI-H727) and AC (NCI-H720) cell lines and patient-derived cell cultures in Tg(fli1a:EGFP)y1 zebrafish embryos. We exploited this platform to test the anti-tumor activity of sulfatinib. The tumorigenic potential of TC and AC implanted cells was evaluated by the quantification of tumor-induced angiogenesis and tumor cell migration as early as 24 h post-injection (hpi). The characterization of tumor-induced angiogenesis was performed in vivo and in real time, coupling the tumor xenograft with selective plane illumination microscopy on implanted zebrafish embryos. TC-implanted cells displayed a higher pro-angiogenic potential compared to AC cells, which inversely showed a relevant migratory behavior within 48 hpi. Sulfatinib inhibited tumor-induced angiogenesis, without affecting tumor cell spread in both TC and AC implanted embryos. In conclusion, zebrafish embryos implanted with TC and AC cells faithfully recapitulate the tumor behavior of human lung carcinoids and appear to be a promising platform for drug screening.
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Affiliation(s)
- Silvia Carra
- Laboratory of Endocrine and Metabolic Research, IRCCS, Istituto Auxologico Italiano, 20100 Milan, Italy; (S.C.); (L.P.)
| | - Germano Gaudenzi
- Laboratory of Geriatric and Oncologic Neuroendocrinology Research, IRCCS, Istituto Auxologico Italiano, 20100 Milan, Italy; (G.G.); (M.C.C.); (A.P.)
| | - Alessandra Dicitore
- Department of Medical Biotechnology and Translational Medicine, University of Milan, 20100 Milan, Italy; (A.D.); (D.S.)
| | - Maria Celeste Cantone
- Laboratory of Geriatric and Oncologic Neuroendocrinology Research, IRCCS, Istituto Auxologico Italiano, 20100 Milan, Italy; (G.G.); (M.C.C.); (A.P.)
| | - Alice Plebani
- Laboratory of Geriatric and Oncologic Neuroendocrinology Research, IRCCS, Istituto Auxologico Italiano, 20100 Milan, Italy; (G.G.); (M.C.C.); (A.P.)
| | - Davide Saronni
- Department of Medical Biotechnology and Translational Medicine, University of Milan, 20100 Milan, Italy; (A.D.); (D.S.)
- PhD Program in Experimental Medicine, University of Milan, 20100 Milan, Italy
| | - Silvia Zappavigna
- Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy; (S.Z.); (M.C.)
| | - Michele Caraglia
- Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy; (S.Z.); (M.C.)
- Laboratory of Molecular and Precision Oncology, Biogem scarl, 83031 Ariano Irpino, Italy
| | - Alessia Candeo
- Department of Physics, Politecnico di Milano, 20133 Milan, Italy; (A.C.); (A.B.)
| | - Andrea Bassi
- Department of Physics, Politecnico di Milano, 20133 Milan, Italy; (A.C.); (A.B.)
| | - Luca Persani
- Laboratory of Endocrine and Metabolic Research, IRCCS, Istituto Auxologico Italiano, 20100 Milan, Italy; (S.C.); (L.P.)
- Department of Medical Biotechnology and Translational Medicine, University of Milan, 20100 Milan, Italy; (A.D.); (D.S.)
| | - Giovanni Vitale
- Laboratory of Geriatric and Oncologic Neuroendocrinology Research, IRCCS, Istituto Auxologico Italiano, 20100 Milan, Italy; (G.G.); (M.C.C.); (A.P.)
- Department of Medical Biotechnology and Translational Medicine, University of Milan, 20100 Milan, Italy; (A.D.); (D.S.)
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Ramachandran A, Madhusudhan KS. Advances in the imaging of gastroenteropancreatic neuroendocrine neoplasms. World J Gastroenterol 2022; 28:3008-3026. [PMID: 36051339 PMCID: PMC9331531 DOI: 10.3748/wjg.v28.i26.3008] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 11/30/2021] [Accepted: 06/20/2022] [Indexed: 02/06/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms comprise a heterogeneous group of tumors that differ in their pathogenesis, hormonal syndromes produced, biological behavior and consequently, in their requirement for and/or response to specific chemotherapeutic agents and molecular targeted therapies. Various imaging techniques are available for functional and morphological evaluation of these neoplasms and the selection of investigations performed in each patient should be customized to the clinical question. Also, with the increased availability of cross sectional imaging, these neoplasms are increasingly being detected incidentally in routine radiology practice. This article is a review of the various imaging modalities currently used in the evaluation of neuroendocrine neoplasms, along with a discussion of the role of advanced imaging techniques and a glimpse into the newer imaging horizons, mostly in the research stage.
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Affiliation(s)
- Anupama Ramachandran
- Department of Radiodiagnosis and Interventional Radiology, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Kumble Seetharama Madhusudhan
- Department of Radiodiagnosis and Interventional Radiology, All India Institute of Medical Sciences, New Delhi 110029, India
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van der Velden D, Staal F, Aalbersberg E, Castagnoli F, Wilthagen E, Beets-Tan R. Prognostic value of CT characteristics in GEP-NET: a systematic review. Crit Rev Oncol Hematol 2022; 175:103713. [DOI: 10.1016/j.critrevonc.2022.103713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 05/04/2022] [Accepted: 05/16/2022] [Indexed: 11/16/2022] Open
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Wang L, Nie F, Dong T, Yin C, Li M, Li Y. Nonhypovascular pancreatic ductal adenocarcinomas: CEUS imaging findings and differentiation from other types of solid pancreatic lesions. Clin Hemorheol Microcirc 2022; 81:163-176. [PMID: 35253738 DOI: 10.3233/ch-221397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVES To observe and assess the diagnostic value of contrast-enhanced ultrasound (CEUS) in patients with iso-/hypervascular solid pancreatic lesions. METHODS 70 pancreatic lesions (all confirmed by surgery or biopsy pathology) that manifested iso-/hyperenhancement on CEUS were retrospectively studied from January 2018 to January 2022, including 24 pancreatic ductal adenocarcinomas (PDAC), 15 mass-forming pancreatitis (MFP), 24 pancreatic neuroendocrine tumors (PNET) (14 hyper-PNETs, 10 iso-PNETs), and 7 solid pseudopapillary tumors of pancreas (SPTP). 65 pancreatic ductal adenocarcinomas (PDAC) that manifested hypoenhancement on CEUS were retrospectively studied from January 2020 to January 2022. CEUS patterns and the clinical and pathologic features were analyzed, and the diagnostic ability of CEUS for iso/hyperenhanced solid pancreatic lesions was assessed. RESULTS Centripetal enhancement, heterogeneous enhancement, early washout, and hypoenhancement in the late phase mostly appeared in iso-/hyper-PDACs (p < 0.05). Heterogeneous enhancement in small lesions (< 3 cm) as the diagnostic criterion for iso-/hyper-PDACs had an accuracy of 74.3% and a specificity of 91.3%. Iso-PNETs more commonly had larger tumor sizes and more often showed heterogeneous enhancement than hyper-PNETs (p = 0.007, p = 0.035, respectively). The characteristics of the combination of isoenhancement, homogeneous enhancement, and synchronous wash-in/out for MFP had a high accuracy of 90%. Capsular enhancement with heterogeneous enhancement inside for SPTP had an accuracy of 97.1%. CONCLUSION CEUS enhancement patterns have potentially great value in the differentiation of iso-/hyperenhanced pancreatic lesions.
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Affiliation(s)
- Lan Wang
- Ultrasound Medical Center, Lanzhou University Second Hospital, Cuiyingmen, Chengguan District, Lanzhou, China. Gansu Province Clinical Research Center for Ultrasonography, Lanzhou, China
| | - Fang Nie
- Ultrasound Medical Center, Lanzhou University Second Hospital, Cuiyingmen, Chengguan District, Lanzhou, China. Gansu Province Clinical Research Center for Ultrasonography, Lanzhou, China
| | - Tiantian Dong
- Ultrasound Medical Center, Lanzhou University Second Hospital, Cuiyingmen, Chengguan District, Lanzhou, China. Gansu Province Clinical Research Center for Ultrasonography, Lanzhou, China
| | - Ci Yin
- Ultrasound Medical Center, Lanzhou University Second Hospital, Cuiyingmen, Chengguan District, Lanzhou, China. Gansu Province Clinical Research Center for Ultrasonography, Lanzhou, China
| | - Ming Li
- Ultrasound Medical Center, Lanzhou University Second Hospital, Cuiyingmen, Chengguan District, Lanzhou, China. Gansu Province Clinical Research Center for Ultrasonography, Lanzhou, China
| | - Yuanyuan Li
- Ultrasound Medical Center, Lanzhou University Second Hospital, Cuiyingmen, Chengguan District, Lanzhou, China. Gansu Province Clinical Research Center for Ultrasonography, Lanzhou, China
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Jubashi A, Yamaguchi D, Ogata R, Nagatsuma G, Hara Y, Tanaka Y, Yoshioka W, Hino N, Morisaki T, Ario K, Matsuoka Y, Taba M, Naito S, Tsunada S. A case of pancreatic endocrine carcinoma with a different clinical diagnosis before chemotherapy and pathological autopsy. Clin J Gastroenterol 2021; 15:237-243. [PMID: 34689312 DOI: 10.1007/s12328-021-01538-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Accepted: 10/14/2021] [Indexed: 11/29/2022]
Abstract
We encountered a case of pancreatic neuroendocrine carcinoma (pNEC) diagnosed via pathological autopsy that was initially diagnosed clinically as G3 pancreatic neuroendocrine tumor (G3 pNET) and discussed the differences between these entities in the literature. A 76-year-old man was admitted to our department because of jaundice. Computed tomography revealed multiple round nodules in both lung fields, suggesting metastasis, and a mass lesion was detected in the head of the pancreas with poor contrast in the arterial phase and slight contrast enhancement in the equilibrium phase. Biopsy of the lungs and pancreas led to a diagnosis of multiple pulmonary metastases of G3 pNET. Because the lesions were unresectable, chemotherapy was administered. Treatment was started with everolimus for 5 weeks. However, the patient experienced severe loss of appetite and malaise, and the lung lesions progressed, prompting treatment discontinuation. Subsequently, the patient's disease progressed rapidly, and he died 99 days after the start of chemotherapy. We performed a pathological autopsy with the consent of the family because of the rapid tumor growth. A pathological autopsy revealed a final diagnosis of pNEC, which differed from the clinical diagnosis.
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Affiliation(s)
- Amane Jubashi
- Department of Gastroenterology, National Hospital Organization Ureshino Medical Center, Ureshino, Japan.,Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Daisuke Yamaguchi
- Department of Gastroenterology, National Hospital Organization Ureshino Medical Center, Ureshino, Japan. .,Division of Gastroenterology, Department of Internal Medicine, Saga University, Saga, 849-8501, Japan.
| | - Ryo Ogata
- Department of Gastroenterology, National Hospital Organization Ureshino Medical Center, Ureshino, Japan
| | - Goshi Nagatsuma
- Department of Gastroenterology, National Hospital Organization Ureshino Medical Center, Ureshino, Japan
| | - Yumi Hara
- Department of Gastroenterology, National Hospital Organization Ureshino Medical Center, Ureshino, Japan
| | - Yuichiro Tanaka
- Department of Gastroenterology, National Hospital Organization Ureshino Medical Center, Ureshino, Japan
| | - Wataru Yoshioka
- Department of Gastroenterology, National Hospital Organization Ureshino Medical Center, Ureshino, Japan
| | - Naoyuki Hino
- Department of Gastroenterology, National Hospital Organization Ureshino Medical Center, Ureshino, Japan
| | - Tomohito Morisaki
- Department of Gastroenterology, National Hospital Organization Ureshino Medical Center, Ureshino, Japan
| | - Keisuke Ario
- Department of Gastroenterology, National Hospital Organization Ureshino Medical Center, Ureshino, Japan
| | - Yuki Matsuoka
- Department of Pathology, National Hospital Organization Ureshino Medical Center, Ureshino, Japan
| | - Mitsuru Taba
- Department of Pathology, National Hospital Organization Ureshino Medical Center, Ureshino, Japan
| | - Shinji Naito
- Department of Pathology, National Hospital Organization Ureshino Medical Center, Ureshino, Japan
| | - Seiji Tsunada
- Department of Gastroenterology, National Hospital Organization Ureshino Medical Center, Ureshino, Japan
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Han S, Kim JH, Yoo J, Jang S. Prediction of recurrence after surgery based on preoperative MRI features in patients with pancreatic neuroendocrine tumors. Eur Radiol 2021; 32:2506-2517. [PMID: 34647178 DOI: 10.1007/s00330-021-08316-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 09/01/2021] [Accepted: 09/04/2021] [Indexed: 10/20/2022]
Abstract
OBJECTIVES To investigate useful MRI features in pancreatic neuroendocrine tumor (PNET) patients for predicting recurrence and its timing after surgery. METHODS A total of 99 patients with PNET who underwent MRI and surgery from 2000 to 2018 were enrolled. Two radiologists independently assessed MRI findings, including size, location, margin, T1 and T2 signal intensity, enhancement patterns, common bile duct (CBD) or main pancreatic duct (MPD) dilatation, vascular invasion, lymph node enlargement, DWI, and ADC value. Imaging findings associated with recurrence and disease-free survival (DFS) were assessed using logistic regression analysis and Cox proportional hazard regression analysis. RESULTS The median follow-up period was 40.4 months, and recurrence after surgery occurred in 12.1% (12/99). Among them, 6 patients experienced recurrence within 1 year, and 9 patients experienced recurrence within 2 years after surgery. In multivariate analysis, major venous invasion (OR 10.76 [1.14-101.85], p = 0.04) was associated with recurrence within 1 year, and portal phase iso- to hypoenhancement (OR 51.89 [1.73-1557.89], p = 0.02), CBD or MPD dilatation (OR 10.49 [1.35-81.64], p = 0.03) and larger size (OR 1.05 [1.00-1.10], p = 0.046) were associated with recurrence within 2 years. The mean DFS was 116.4 ± 18.5 months, and the 5-year DFS rate was 85.7%. In multivariate analysis, portal phase iso- to hypoenhancement (HR 21.36 [2.01-197.77], p = 0.01), ductal dilatation (HR 5.22 [1.46-18.68], p = 0.01), major arterial invasion (HR 42.90 [3.66-502.48], p = 0.003), and larger size (HR 1.04 [1.01-1.06], p = 0.01) showed a significant effect on poor DFS. CONCLUSION MRI features, including size, enhancement pattern, vascular invasion, and ductal dilatation, are useful in predicting recurrence and poor DFS after surgery in PNET. Key Points • MRI features are useful for predicting prognosis in patients with PNET after surgery. • PV or SMV invasion (OR 10.49 [1.35-81.64], p = 0.04) was significantly associated with 1-year recurrence. • Portal phase iso- to hypoenhancement (HR 21.36), CBD or MPD dilatation (HR 5.22), arterial invasion (HR 42.90), and larger size (HR 1.04) had significant effects on poor DFS (p < 0.05).
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Affiliation(s)
- Seungchul Han
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Jung Hoon Kim
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea. .,Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. .,Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea.
| | - Jeongin Yoo
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Siwon Jang
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.,Department of Radiology, Seoul National University Boramae Hospital, Seoul, Republic of Korea
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Yang D, Wang D, Qiu Y, Tian X, Zuo D, Dong Y, Lou W, Wang W. Incidental nonfunctioning pancreatic neuroendocrine tumors: Contrast enhanced ultrasound features in diagnosis. Clin Hemorheol Microcirc 2021; 80:343-352. [PMID: 34602462 DOI: 10.3233/ch-211269] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
AIM Preoperative suspicion of malignancy in nonfunctioning pancreatic neuroendocrine tumors (pNETs) is mostly based on tumor size. We retrospectively analyzed the contrast enhanced ultrasound (CEUS) features of a series of histopathologically proved nonfunctioning pNETs. METHODS In this retrospective study, 37 surgery and histologically proved nonfunctioning pNETs were included. All pNETs lesions were incidentally detected by transabdominal ultrasound. B mode ultrasound (BMUS) and CEUS features were reviewed and analyzed. 52 histopathologically proved pancreatic ductal adenocarcinoma (PDACs) lesions were included as a control group. RESULTS All nonfunctioning pNETs patients showed no typical clinical symptoms. No significant differences were observed in size, echogenicity or internal color flow imaging signal between pNETs and PDAC patients (P > 0.05). Most of nonfunctioning pNETs showed a well-defined tumor margin. The presence of pancreatic duct dilatation was less frequently observed in nonfunctioning pNETs patients (P < 0.05). After injection of ultrasound contrast agents, homogeneous enhancement was more commonly observed in nonfunctioning pNETs group (P < 0.05). During arterial phase of CEUS, most of nonfunctioning pNETs were hyper- or isoenhanced (32/37, 86.5%), whereas most of PDACs were hypoenhanced (34/52, 65.4%) (P < 0.05). Nonenhanced necrosis area was more commonly detected in PDACs (P = 0.012). CONCLUSIONS CEUS features are helpful for preoperative non-invasive differential diagnosis of nonfunctioning pNETs, assisting further clinical decision-making process.
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Affiliation(s)
- Daohui Yang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Dansong Wang
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yijie Qiu
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiaofan Tian
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Dan Zuo
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yi Dong
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wenhui Lou
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wenping Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
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Vullierme MP, Ruszniewski P, de Mestier L. Are recist criteria adequate in assessing the response to therapy in metastatic NEN? Rev Endocr Metab Disord 2021; 22:637-645. [PMID: 33871762 DOI: 10.1007/s11154-021-09645-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/08/2021] [Indexed: 10/21/2022]
Abstract
Response to therapy criteria, known as RECIST (Response Evaluation Criteria in Solid Tumours), are widely used to evaluate neuroendocrine tumours (NET) metastatic to the liver, under treatment. RECIST criteria does not take in account many various distinct features such as tumour growth, secretory capacity and anatomical localisation with wide variation in clinical and biological presentation of different NETs. Key features of RECIST includes definitions of the minimal size of measurable lesions, instructions on how many lesions to measure and follow, and the use of unidimensional, rather than bidimensional, measures for overall evaluation of tumour burden. These measures are currently done with computed tomography (CT) or Magnetic Resonance Imaging (MRI). RECIST criteria are accurate in assessing tumour progression but sometimes inaccurate in assessing tumour response after locoregional therapy or under molecular targeted therapy, tumour vessels being part of the target of such treatments. There is poor correlation between a so called tumour necrosis and conventional methods of response assessment, which poses questions of how best to quantify efficacy of these targeted therapies. Variations in tumour density with computed tomography (CT) could theoretically be associated with tumour necrosis. This hypothesis has been studied proposing alternative CT criteria of response evaluation in metastatic digestive NET treated with targeted therapy. If preliminary results upon the poor relationship between density measured with CT (derived from CHOI criteria) evolution curves at CT and PFS are confirmed by further studies, showing that the correlation between density changing and response to non-targeted treatment is weak, the use of contrast injection, will probably be not mandatory to enable appropriate evaluation.
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Affiliation(s)
- Marie-Pierre Vullierme
- Department of Radiology, University Hospitals Paris-Nord Val-de-Seine, AP-HP, Beaujon, 92110, Clichy, France.
- Université Paris Diderot-Paris 7, University of Paris, 75018, Clichy, France.
| | - Philippe Ruszniewski
- Department of Pancreatology, University Hospitals Paris-Nord Val-de-Seine, AP-HP, Beaujon, 92110, Clichy, France
- Université Paris Diderot-Paris 7, University of Paris, 75018, Clichy, France
| | - Louis de Mestier
- Department of Pancreatology, University Hospitals Paris-Nord Val-de-Seine, AP-HP, Beaujon, 92110, Clichy, France
- Université Paris Diderot-Paris 7, University of Paris, 75018, Clichy, France
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23
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Target Heterogeneity in Oncology: The Best Predictor for Differential Response to Radioligand Therapy in Neuroendocrine Tumors and Prostate Cancer. Cancers (Basel) 2021; 13:cancers13143607. [PMID: 34298822 PMCID: PMC8304541 DOI: 10.3390/cancers13143607] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 07/04/2021] [Accepted: 07/07/2021] [Indexed: 12/27/2022] Open
Abstract
Simple Summary In the era of precision medicine, novel targets have emerged on the surface of cancer cells, which have been exploited for the purpose of radioligand therapy. However, there have been variations in the way these receptors are expressed, especially in prostate cancers and neuroendocrine tumors. This variable expression of receptors across the grades of cancers led to the concept of ‘target heterogeneity’, which has not just impacted therapeutic decisions but also their outcomes. Radiopharmaceuticals targeting receptors need to be used when there are specific indicators—either clinical, radiological, or at molecular level—warranting their use. In addition, response to these radioligands can be assessed using different techniques, whereby we can prognosticate further outcomes. We shall also discuss, in this review, the conventional as well as novel approaches of detecting heterogeneity in prostate cancers and neuroendocrine tumors. Abstract Tumor or target heterogeneity (TH) implies presence of variable cellular populations having different genomic characteristics within the same tumor, or in different tumor sites of the same patient. The challenge is to identify this heterogeneity, as it has emerged as the most common cause of ‘treatment resistance’, to current therapeutic agents. We have focused our discussion on ‘Prostate Cancer’ and ‘Neuroendocrine Tumors’, and looked at the established methods for demonstrating heterogeneity, each with its advantages and drawbacks. Also, the available theranostic radiotracers targeting PSMA and somatostatin receptors combined with targeted systemic agents, have been described. Lu-177 labeled PSMA and DOTATATE are the ‘standard of care’ radionuclide therapeutic tracers for management of progressive treatment-resistant prostate cancer and NET. These approved therapies have shown reasonable benefit in treatment outcome, with improvement in quality of life parameters. Various biomarkers and predictors of response to radionuclide therapies targeting TH which are currently available and those which can be explored have been elaborated in details. Imaging-based features using artificial intelligence (AI) need to be developed to further predict the presence of TH. Also, novel theranostic tools binding to newer targets on surface of cancer cell should be explored to overcome the treatment resistance to current treatment regimens.
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24
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Noguchi T, Ryozawa S, Mizuide M, Tanisaka Y, Fujita A, Ogawa T, Suzuki M, Katsuda H, Nagata K, Kawasaki T, Aikawa M, Okamoto K. Pancreatic Hamartoma Difficult to Diagnose Preoperatively. Intern Med 2021; 60:2055-2059. [PMID: 33518562 PMCID: PMC8313911 DOI: 10.2169/internalmedicine.5982-20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Abdominal ultrasonography in a 70-year-old woman showed a hypoechoic mass, 14 mm in diameter, in the pancreatic body. Computed tomography showed a mass with contrast effect in the pancreatic body. Test results for endocrine factors or tumor markers were normal. The initial consideration was nonfunctional pancreatic neuroendocrine tumor. Over 8 years of monitoring, the tumor diameter increased to 18 mm, until pancreatic tumor enucleation was performed. The postoperative diagnosis was pancreatic hamartoma, a rare type of benign pancreatic tumor. The preoperative diagnosis of pancreatic hamartoma is difficult, but consideration must be given to the possibility of hamartoma when encountering pancreatic tumors.
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Affiliation(s)
- Tatsuya Noguchi
- Department of Gastroenterology, Saitama Medical University International Medical Center, Japan
| | - Shomei Ryozawa
- Department of Gastroenterology, Saitama Medical University International Medical Center, Japan
| | - Masafumi Mizuide
- Department of Gastroenterology, Saitama Medical University International Medical Center, Japan
| | - Yuki Tanisaka
- Department of Gastroenterology, Saitama Medical University International Medical Center, Japan
| | - Akashi Fujita
- Department of Gastroenterology, Saitama Medical University International Medical Center, Japan
| | - Tomoya Ogawa
- Department of Gastroenterology, Saitama Medical University International Medical Center, Japan
| | - Masahiro Suzuki
- Department of Gastroenterology, Saitama Medical University International Medical Center, Japan
| | - Hiromune Katsuda
- Department of Gastroenterology, Saitama Medical University International Medical Center, Japan
| | - Koji Nagata
- Department of Pathology, Nippon Medical School Tama Nagayama Hospital, Japan
| | - Tomonori Kawasaki
- Department of Pathology, Saitama Medical University International Medical Center, Japan
| | - Masayasu Aikawa
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Japan
| | - Kojun Okamoto
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Japan
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25
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Prognostic significance of extracellular volume fraction with equilibrium contrast-enhanced computed tomography for pancreatic neuroendocrine neoplasms. Pancreatology 2021; 21:779-786. [PMID: 33714670 DOI: 10.1016/j.pan.2021.02.020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Revised: 02/21/2021] [Accepted: 02/25/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND /Objectives: Identifying reliable pretreatment imaging biomarkers for pancreatic neuroendocrine neoplasm (PanNEN) is a key imperative. Extracellular volume (ECV) fraction quantified with equilibrium contrast-enhanced CT can be easily integrated into routine examinations. This study aimed to determine whether ECV fraction with equilibrium contrast-enhanced computed tomography (CECT) could predict long-term outcomes in patients with PanNEN. METHODS This study was a retrospective observational study of 80 patients pathologically diagnosed with PanNEN at a single institution. ECV fraction of the primary lesion was calculated using region-of-interest measurement within PanNEN and the aorta on unenhanced and equilibrium CECT. The impact of clinical factors and tumor ECV fraction on progression-free survival (PFS) and overall survival (OS) was assessed with univariate and multivariate analyses using Cox proportional hazards models. The correlation between WHO classification and tumor ECV fraction was evaluated using Kendall rank correlation coefficients. RESULTS PFS and OS rates were estimated as 93.4% and 94.6%, 78.7% and 86.2%, 78.7% and 77.0%, and 78.7% and 66.6% at 1, 3, 5, and 10 years, respectively. Multivariate analysis revealed that Union for International Cancer Control (UICC) stage (hazard ratio [HR] = 3.95, P = 0.003), WHO classification (HR = 12.27, P = 0.003), and tumor ECV fraction (HR = 11.93, P = 0.039) were independent predictors of PFS. Patient age (HR = 1.11, P < 0.001), UICC stage (HR = 3.14, P = 0.001), and tumor ECV fraction (HR = 5.27, P = 0.024) were independent significant variables for predicting OS. Tumor ECV fraction had a weak inverse relationship with WHO classification (P = 0.045, τ = -0.178). CONCLUSIONS ECV fraction determined by equilibrium CECT and UICC stage may predict survival in patients with PanNEN.
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26
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Tanaka M, Koji I, Fujioka I, Sato M, Hirose K, Kawaguchi H, Hatayama Y, Takai Y, Tsushima E, Aoki M. Impact of low iodine density tumor area ratio on the local control of non-small cell lung cancer through stereotactic body radiotherapy. JOURNAL OF RADIATION RESEARCH 2021; 62:448-456. [PMID: 33823009 PMCID: PMC8127655 DOI: 10.1093/jrr/rrab015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 01/06/2021] [Indexed: 05/09/2023]
Abstract
Lung cancer with low average iodine density measured via contrast-enhanced computed tomography (CT) using dual-energy CT technology has shown a reduced local control rate after stereotactic body radiotherapy (SBRT). The current study therefore investigated the relationship between low iodine density tumor area and its ratio and local recurrence after SBRT. Dual-energy CT was performed on the day before SBRT initiation, with a low iodine density tumor area being defined as that with an iodine density of <1.81 mg cm-3. The low iodine density tumor area, the ratio between the low iodine density tumor area and the entire tumor, and the local recurrence rate were then determined. No correlation was observed between the low iodine density tumor area and the local recurrence rate. However, tumors with a large low iodine density tumor area ratio showed an increased local recurrence rate, with the prognostic accuracy almost similar to that in previous studies using average iodine densities. Our results therefore suggest that the low iodine density tumor area ratio was a useful prognostic index after SBRT, with an accuracy comparable with that of the average iodine density.
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Affiliation(s)
- Mitsuki Tanaka
- Department of Radiation Oncology, Graduate School of Medicine, Hirosaki University, 5 Zaifu-cho, Hirosaki, Aomori, 036-8216 Japan
| | - Ichise Koji
- Department of Radiation Oncology, Graduate School of Medicine, Hirosaki University, 5 Zaifu-cho, Hirosaki, Aomori, 036-8216 Japan
| | - Ichitaro Fujioka
- Department of Radiation Oncology, Graduate School of Medicine, Hirosaki University, 5 Zaifu-cho, Hirosaki, Aomori, 036-8216 Japan
| | - Mariko Sato
- Department of Radiation Oncology, Graduate School of Medicine, Hirosaki University, 5 Zaifu-cho, Hirosaki, Aomori, 036-8216 Japan
- Department of Radiation Oncology, Southern Tohoku BNCT Research Center, 7-10 Yatsuyamada, Koriyama, Fukushima, 963-8052 Japan
| | - Katsumi Hirose
- Department of Radiation Oncology, Graduate School of Medicine, Hirosaki University, 5 Zaifu-cho, Hirosaki, Aomori, 036-8216 Japan
- Department of Radiation Oncology, Southern Tohoku BNCT Research Center, 7-10 Yatsuyamada, Koriyama, Fukushima, 963-8052 Japan
| | - Hideo Kawaguchi
- Department of Radiation Oncology, Graduate School of Medicine, Hirosaki University, 5 Zaifu-cho, Hirosaki, Aomori, 036-8216 Japan
| | - Yoshiomi Hatayama
- Department of Radiation Oncology, Graduate School of Medicine, Hirosaki University, 5 Zaifu-cho, Hirosaki, Aomori, 036-8216 Japan
| | - Yoshihiro Takai
- Department of Radiation Oncology, Graduate School of Medicine, Hirosaki University, 5 Zaifu-cho, Hirosaki, Aomori, 036-8216 Japan
- Department of Radiation Oncology, Southern Tohoku BNCT Research Center, 7-10 Yatsuyamada, Koriyama, Fukushima, 963-8052 Japan
| | - Eiki Tsushima
- Department of Physical Therapy, Graduate School of Health Sciences, Hirosaki University, 66-1 Hon-cho, Hirosaki, Aomori, 036-8564 Japan
| | - Masahiko Aoki
- Corresponding author. Department of Radiation Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562 Japan. Tel: +81-172-39-5103; Fax: +81-172-33-5627; E-mail:
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27
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Muehler MR, Rendell VR, Bergmann LL, Winslow ER, Reeder SB. Ferumoxytol-enhanced MR imaging for differentiating intrapancreatic splenules from other tumors. Abdom Radiol (NY) 2021; 46:2003-2013. [PMID: 33377995 PMCID: PMC8131292 DOI: 10.1007/s00261-020-02883-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 11/19/2020] [Accepted: 11/25/2020] [Indexed: 12/21/2022]
Abstract
Objectives Ferumoxytol is an ultra-small superparamagnetic iron oxide (USPIO) agent that is taken up by splenic tissue. This study describes our initial institutional experience of ferumoxytol-enhanced MRI (feMRI) for differentiating intrapancreatic splenules (IPS) from other pancreatic lesions. Methods In this retrospective study, patients with computed tomographic imaging that identified small enhancing lesions in the tail of the pancreas subsequently underwent feMRI for further characterization. The feMRI protocol included T2-weighted (T2w) imaging with and without fat suppression (FS), R2* mapping, diffusion-weighted imaging (DWI), and T1-weighted (T1w) imaging with FS, prior to contrast injection. Immediately after slow intravenous infusion with 3 mg/kg body weight ferumoxytol, T1w was repeated. Delayed imaging with all sequences were obtained 24–72 h after ferumoxytol administration. Results Seven patients underwent feMRI. In two patients, the pancreatic lesions were presumed as pancreatic neuroendocrine tumor (PNET) from feMRI and in the remaining 5 IPS. One of the two patients with PNET was symptomatic for NET. In another symptomatic patient with pathologically proven duodenal NET and suspected PNET, the pancreatic lesion was proven to be an IPS on feMRI. IPS demonstrated strong negative enhancement in feMRI on T2w and increased R2* values consistent with splenic tissue, while the presumed PNETs did not enhance. T2w FS was helpful on the pre-contrast images to identify IPS, while R2* did on post-contrast images. Neither DWI nor T1w contributed to differentiating PNETs from IPS. Conclusions This study demonstrates the potential utility of feMRI as a helpful adjunct diagnostic tool for differentiating IPS from other pancreatic lesions. Further studies in larger patient cohorts are needed.
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Affiliation(s)
- M R Muehler
- Department of Radiology, University of Wisconsin, Madison, WI, USA.
- Department of Radiology and Neuroradiology, University Greifswald, Greifswald, Germany.
| | - V R Rendell
- Department of Surgery, University of Wisconsin, Madison, WI, USA
| | - L L Bergmann
- Department of Radiology, University of Texas Southwestern, Dallas, TX, USA
| | - E R Winslow
- Medstar Georgetown Transplant Institute, Medstar Georgetown University Hospital, Washington, DC, USA
| | - S B Reeder
- Department of Radiology, University of Wisconsin, Madison, WI, USA
- Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA
- Department Medical Physics, University of Wisconsin, Madison, WI, USA
- Department of Medicine, University of Wisconsin, Madison, WI, USA
- Department of Emergency Medicine, University of Wisconsin, Madison, WI, USA
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28
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Li WX, Miao F, Xu XQ, Zhang J, Wu ZY, Chen KM, Yan FH, Lin XZ. Pancreatic Neuroendocrine Neoplasms: CT Spectral Imaging in Grading. Acad Radiol 2021; 28:208-216. [PMID: 32111466 DOI: 10.1016/j.acra.2020.01.033] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Revised: 01/26/2020] [Accepted: 01/26/2020] [Indexed: 12/20/2022]
Abstract
RATIONALE AND OBJECTIVES The purpose of this study was to define the CT spectral imaging characteristics of pancreatic neuroendocrine neoplasms (PNENs) and evaluate their potential for differential diagnosis of nonlow grade (non-LG) PNENs from low grade (LG) PNENs. MATERIALS AND METHODS CT spectral imaging data of 54 pathologically proven PNENs were retrospectively reviewed. Patients were divided into two groups: 40 cases with grade 1 in LG PNENs group and 14 cases with grade 2 and grade 3 in non-LG PNENs group. RESULTS Gender, calcification, inhomogeneity, invasiveness, PD dilatation, lymph node enlargement, size, normalized iodine (water) concentration in arterial phase (AP) (Iodine (ap)), normalized effective-Z (Zap), slope of normalized CT spectral curves in both AP, and portal venous phase were found to be significant variables for differentiating non-LG PNENs from LG PNENs (p < 0.05). Non-LG PNENs had larger size and lower Zap and Iodine (ap) than LG PNENs. The tumor size, Zap and Iodine (ap) had fair to good diagnostic performance with the area under receiver-operating-characteristic curve (AUC) 0.843, 0.733, and 0.728, respectively. Multivariate analysis with logistic regression had higher AUC (p<0.05) than all the single parameters except for size. CONCLUSION There were significant differences in CT spectral imaging parameters between non-LG and LG PNENs. Tumor size was the most promising independent parameter and the combination of quantitative parameters with qualitative parameters is the best predictor in differentiating of non-LG PNENs from LG PNENs. CT spectral imaging can help determine the malignancy of PNENs, which can better assist in surgical planning.
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Affiliation(s)
- Wei-Xia Li
- Department of Radiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Fei Miao
- Department of Radiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Xue-Qin Xu
- Department of Radiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jing Zhang
- Department of Radiology, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Jiading, Shanghai, China
| | - Zhi-Yuan Wu
- Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Ke-Min Chen
- Department of Radiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Fu-Hua Yan
- Department of Radiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Xiao-Zhu Lin
- Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 2nd Ruijin Road, Shanghai, China.
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29
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Wang Y, Chen X, Wang J, Cui W, Wang C, Chen X, Wang Z. Differentiation between non-hypervascular pancreatic neuroendocrine tumors and mass-forming pancreatitis using contrast-enhanced computed tomography. Acta Radiol 2021; 62:190-197. [PMID: 32375515 DOI: 10.1177/0284185120921503] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Non-hypervascular pancreatic neuroendocrine tumors (PNETs) showed slight or iso-enhancement in contrast-enhanced computed tomography (CE-CT), which shared similar imaging findings with mass-forming pancreatitis (MFPs). PURPOSE To explore the value of CT imaging features in differentiating the two diseases. MATERIAL AND METHODS Fifty-one patients with histologically proved MFPs (n = 27) or non-hypervascular PNETs (n = 24) were included. Two radiologists reviewed CT imaging findings and clinical features. Logistic regression analysis was performed to identify relevant features in differentiating non-hypervascular PNETs and MFPs. Receiver operating characteristic (ROC) curve analysis was used to show the performance of the optimal parameters in differentiating non-hypervascular PNETs and MFPs. RESULTS A well-defined margin was more common in non-hypervascular PNETs (P < 0.05) than that in MFPs. MFPs often occurred in older people (P < 0.01) and the head-neck of the pancreas compared with non-hypervascular PNETs (P < 0.05). Metastases only presented in non-hypervascular PNETs (P < 0.05). CT values at venous phase and delay phase of MFPs were higher (P = 0.010 and P = 0.029) than those in non-hypervascular PNETs. Logistic analysis showed gender, tumor margin, CT values at venous phase, and tumor components were independent predictors in differentiating the two lesions. The area under the curve (AUC) was 0.938 with a sensitivity of 87.5% and specificity of 92.6% for combined predicators. CONCLUSION Gender, tumor margin, CT values at venous phase, and tumor components were useful predicators in differentiating non-hypervascular PNETs and MFPs.
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Affiliation(s)
- Yajie Wang
- Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, PR China
| | - Xin Chen
- Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, PR China
- Department of Graduate, Bengbu Medical College, Bengbu, Anhui Province, PR China
| | - Jianhua Wang
- Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, PR China
| | - Wenjing Cui
- Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, PR China
| | - Cheng Wang
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, PR China
| | - Xiao Chen
- Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, PR China
| | - Zhongqiu Wang
- Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, PR China
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Kimura K, Tsuchiya J, Kitazume Y, Kishino M, Akahoshi K, Kudo A, Tanaka S, Tanabe M, Tateishi U. Dynamic Enhancement Pattern on CT for Predicting Pancreatic Neuroendocrine Neoplasms with Low PAX6 Expression: A Retrospective Observational Study. Diagnostics (Basel) 2020; 10:diagnostics10110919. [PMID: 33182335 PMCID: PMC7695321 DOI: 10.3390/diagnostics10110919] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 11/05/2020] [Accepted: 11/06/2020] [Indexed: 12/20/2022] Open
Abstract
Paired box 6 (PAX6) is a transcription factor that plays a critical role in tumor suppression, implying that the downregulation of PAX6 promotes tumor growth and invasiveness. This study aimed to examine dynamic computed tomography (CT) features for predicting pancreatic neuroendocrine neoplasms (Pan-NENs) with low PAX6 expression. We retrospectively evaluated 51 patients with Pan-NENs without synchronous liver metastasis to assess the pathological expression of PAX6. Two radiologists analyzed preoperative dynamic CT images to determine morphological features and enhancement patterns. We compared the CT findings between low and high PAX6 expression groups. Pathological analysis identified 11 and 40 patients with low and high PAX6 expression, respectively. Iso- or hypoenhancement types in the arterial and portal phases were significantly associated with low PAX6 expression (p = 0.009; p = 0.001, respectively). Low PAX6 Pan-NENs showed a lower portal enhancement ratio than high PAX6 Pan-NENs (p = 0.044). The combination based on enhancement types (iso- or hypoenhancement during arterial and portal phases) and portal enhancement ratio (≤1.22) had 54.5% sensitivity, 92.5% specificity, and 84.3% accuracy in identifying low PAX6 Pan-NENs. Dynamic CT features, including iso- or hypoenhancement types in the arterial and portal phases and lower portal enhancement ratio may help predict Pan-NENs with low PAX6 expression.
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Affiliation(s)
- Koichiro Kimura
- Department of Diagnostic Radiology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 1138510, Japan; (J.T.); (Y.K.); (M.K.); (U.T.)
- Correspondence: ; Tel.: +81-3-5803-5311
| | - Junichi Tsuchiya
- Department of Diagnostic Radiology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 1138510, Japan; (J.T.); (Y.K.); (M.K.); (U.T.)
| | - Yoshio Kitazume
- Department of Diagnostic Radiology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 1138510, Japan; (J.T.); (Y.K.); (M.K.); (U.T.)
| | - Mitsuhiro Kishino
- Department of Diagnostic Radiology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 1138510, Japan; (J.T.); (Y.K.); (M.K.); (U.T.)
| | - Keiichi Akahoshi
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 1138510, Japan; (K.A.); (A.K.); (M.T.)
| | - Atsushi Kudo
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 1138510, Japan; (K.A.); (A.K.); (M.T.)
| | - Shinji Tanaka
- Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 1138510, Japan;
| | - Minoru Tanabe
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 1138510, Japan; (K.A.); (A.K.); (M.T.)
| | - Ukihide Tateishi
- Department of Diagnostic Radiology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 1138510, Japan; (J.T.); (Y.K.); (M.K.); (U.T.)
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Salahshour F, Mehrabinejad MM, Zare Dehnavi A, Alibakhshi A, Dashti H, Ataee MA, Ayoobi Yazdi N. Pancreatic neuroendocrine tumors (pNETs): the predictive value of MDCT characteristics in the differentiation of histopathological grades. Abdom Radiol (NY) 2020; 45:3155-3162. [PMID: 31897681 DOI: 10.1007/s00261-019-02372-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
PURPOSE To investigate the correlation between multiple detector computed tomography (MDCT) features of pancreatic neuroendocrine tumors (pNETs) and histopathologic grade and find valuable imaging criteria for grade prediction. MATERIAL AND METHODS MDCT of 61 patients with 65 masses, which pNETs were approved histopathologically, underwent revision retrospectively. Each MDCT was evaluated for various radiologic characteristics. Absolute and relative (R: tumor/pancreas, D: tumor-pancreas) tumor enhancements were calculated in multiple post contrast phases. RESULTS 61 patients [mean age = 50.70 ± 14.28 y/o and 30(49.2%) were male] were evaluated and classified into 2 groups histopathologically: G1: 32 (49.2%) and G2,3: 33 (50.8%). Significant relationships were observed between histopathologic tumor grade regarding age (p = 0.006), the longest tumor size (p = 0.006), presence of heterogeneity (p < 0.0001), hypodense foci in delayed phase (p = 0.004), lobulation (p = 0.002), vascular encasement (p < 0.0001), adjacent organ invasion (p = 0.01), presence (p < 0.0001) and number (0.02) of liver metastases, presence of lymphadenopathy with short axis of more than 10 mm (LAP) (p = 0.008), pathologic lymph node size (p = 0.004), relative (R and D) (p = 0.05 and 0.02, respectively), and percentage of arterial hyper-enhancing area (p = <0.0001). Tumor grades, however, had no significant relationship with gender, tumor location, tumor outline, calcification, cystic change, or pancreatic (PD) or biliary duct (BD) dilation (p = 0.21, 0.60, 0.05, 0.05 1, 0.10, and 0.51, respectively). Then, we suggested a novel imaging criteria consisting of six parameters (tumor size > 33 mm, relative (R) tumor enhancement in arterial phase ≤ 1.33, relative (D) tumor enhancement in arterial phase ≤ 16.5, percentage of arterial hyper-enhancing area ≤ 75%, vascular encasement, and lobulation), which specificity and accuracy of combination of all findings (6/6) for predicting G2,3 were 100% and 70.1%, respectively. The highest accuracy (84.21%) was seen in combinations of at least 4 of 6 findings, with 80.00% sensitivity, 87.5% specificity, 83.33% PPV, and 84.85% NPV. CONCLUSION We suggested reliable imaging criteria with high specificity and accuracy for predicting the histopathologic grade of pNETs.
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Affiliation(s)
- Faeze Salahshour
- Department of Radiology, School of Medicine, Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, 1419733141, Iran
| | - Mohammad-Mehdi Mehrabinejad
- Department of Radiology, School of Medicine, Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, 1419733141, Iran
- Students Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Zare Dehnavi
- Department of Radiology, School of Medicine, Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, 1419733141, Iran
- Students Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Abbas Alibakhshi
- Hepatobiliary and Liver Transplantation Division, Department of General Surgery, Imam-Khomeini Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Habibollah Dashti
- Hepatobiliary and Liver Transplantation Division, Department of General Surgery, Imam-Khomeini Hospital, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Mohammad-Ali Ataee
- Department of Radiology, School of Medicine, Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, 1419733141, Iran
| | - Niloofar Ayoobi Yazdi
- Department of Radiology, School of Medicine, Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, 1419733141, Iran.
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Ohki K, Igarashi T, Ashida H, Takenaga S, Shiraishi M, Nozawa Y, Ojiri H. Usefulness of texture analysis for grading pancreatic neuroendocrine tumors on contrast-enhanced computed tomography and apparent diffusion coefficient maps. Jpn J Radiol 2020; 39:66-75. [PMID: 32885378 DOI: 10.1007/s11604-020-01038-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 08/21/2020] [Indexed: 10/23/2022]
Abstract
PURPOSE To determine whether texture analysis of contrast-enhanced computed tomography (CECT) and apparent diffusion coefficient (ADC) maps could predict tumor grade (G1 vs G2-3) in patients with pancreatic neuroendocrine tumor (PNET). MATERIALS AND METHODS Thirty-three PNETs (22 G1 and 11 G2-3) were retrospectively reviewed. Fifty features were individually extracted from the arterial and portal venous phases of CECT and ADC maps by two radiologists. Diagnostic performance was assessed by receiver operating characteristic curves while inter-observer agreement was determined by calculating intraclass correlation coefficients (ICCs). RESULTS G2-G3 tumors were significantly larger than G1. Seventeen features significantly differed among the two readers on univariate analysis, with ICCs > 0.6; the largest area under the curve (AUC) for features of each CECT phase and ADC map was log-sigma 1.0 joint-energy = 0.855 for the arterial phase, log-sigma 1.5 kurtosis = 0.860 for the portal venous phase, and log-sigma 1.0 correlation = 0.847 for the ADC map. The log-sigma 1.5 kurtosis of the portal venous phase showed the largest AUC in the CECT and ADC map, and its sensitivity, specificity, and accuracy were 95.5%, 72.7%, and 87.9%, respectively. CONCLUSION Texture analysis may aid in differentiating between G1 and G2-3 PNET.
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Affiliation(s)
- Kazuyoshi Ohki
- Department of Radiology, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, Japan.
| | - Takao Igarashi
- Department of Radiology, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, Japan
| | - Hirokazu Ashida
- Department of Radiology, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, Japan
| | - Shinsuke Takenaga
- Department of Radiology, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, Japan
| | - Megumi Shiraishi
- Department of Radiology, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, Japan
| | - Yosuke Nozawa
- Department of Radiology, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, Japan
| | - Hiroya Ojiri
- Department of Radiology, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, Japan
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Kimura T, Sugimoto M, Takagi T, Suzuki R, Konno N, Asama H, Sato Y, Irie H, Nakamura J, Takasumi M, Hashimoto M, Kato T, Kofunato Y, Kimura T, Yamada S, Hashimoto Y, Marubashi S, Hikichi T, Ohira H. Pancreatic Neuroendocrine Neoplasm Invading the Entire Main Pancreatic Duct Diagnosed by a Preoperative Endoscopic Biopsy. Intern Med 2020; 59:1991-1996. [PMID: 32448838 PMCID: PMC7492121 DOI: 10.2169/internalmedicine.4546-20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2020] [Accepted: 03/27/2020] [Indexed: 11/06/2022] Open
Abstract
A 78-year-old man was referred to our hospital for a detailed examination of a pancreatic tumor that filled the main pancreatic duct (MPD). The histological diagnosis of the endoscopic biopsy specimen was neuroendocrine tumor (NET) G3. The patient subsequently underwent total pancreatectomy. The histological diagnosis of the surgical specimen was also NET G3. This is the first report of a NET that occupied the MPD and was diagnosed by a preoperative endoscopic biopsy through the papilla of Vater. This case is a good example of a histopathological diagnostic method for pancreatic tumors invading the entire MPD.
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Affiliation(s)
- Tomoya Kimura
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
| | - Mitsuru Sugimoto
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
| | - Tadayuki Takagi
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
| | - Rei Suzuki
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
| | - Naoki Konno
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
| | - Hiroyuki Asama
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
| | - Yuki Sato
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
| | - Hiroki Irie
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
| | - Jun Nakamura
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
- Department of Endoscopy, Fukushima Medical University Hospital, Japan
| | - Mika Takasumi
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
| | - Minami Hashimoto
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
- Department of Endoscopy, Fukushima Medical University Hospital, Japan
| | - Tsunetaka Kato
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
| | - Yasuhide Kofunato
- Department of Hepato-Biliary-Pancreatic and Transplant Surgery, School of Medicine, Fukushima Medical University, Japan
| | - Takashi Kimura
- Department of Hepato-Biliary-Pancreatic and Transplant Surgery, School of Medicine, Fukushima Medical University, Japan
| | - Shoki Yamada
- Department of Diagnostic Pathology, School of Medicine, Fukushima Medical University, Japan
| | - Yuko Hashimoto
- Department of Diagnostic Pathology, School of Medicine, Fukushima Medical University, Japan
| | - Shigeru Marubashi
- Department of Hepato-Biliary-Pancreatic and Transplant Surgery, School of Medicine, Fukushima Medical University, Japan
| | - Takuto Hikichi
- Department of Endoscopy, Fukushima Medical University Hospital, Japan
| | - Hiromasa Ohira
- Department of Gastroenterology, School of Medicine, Fukushima Medical University, Japan
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Khanna L, Prasad SR, Sunnapwar A, Kondapaneni S, Dasyam A, Tammisetti VS, Salman U, Nazarullah A, Katabathina VS. Pancreatic Neuroendocrine Neoplasms: 2020 Update on Pathologic and Imaging Findings and Classification. Radiographics 2020; 40:1240-1262. [PMID: 32795239 DOI: 10.1148/rg.2020200025] [Citation(s) in RCA: 76] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Pancreatic neuroendocrine neoplasms (panNENs) are heterogeneous neoplasms with neuroendocrine differentiation that show characteristic clinical, histomorphologic, and prognostic features; genetic alterations; and biologic behavior. Up to 10% of panNENs develop in patients with syndromes that predispose them to cancer, such as multiple endocrine neoplasia type 1, von Hippel-Lindau disease, tuberous sclerosis complex, neurofibromatosis type 1, and glucagon cell adenomatosis. PanNENs are classified as either functioning tumors, which manifest early because of clinical symptoms related to increased hormone production, or nonfunctioning tumors, which often manifest late because of mass effect. PanNENs are histopathologically classified as well-differentiated pancreatic neuroendocrine tumors (panNETs) or poorly differentiated pancreatic neuroendocrine carcinomas (panNECs) according to the 2010 World Health Organization (WHO) classification system. Recent advances in cytogenetics and molecular biology have shown substantial heterogeneity in panNECs, and a new tumor subtype, well-differentiated, high-grade panNET, has been introduced. High-grade panNETs and panNECs are two distinct entities with different pathogenesis, clinical features, imaging findings, treatment options, and prognoses. The 2017 WHO classification system and the eighth edition of the American Joint Committee on Cancer staging system include substantial changes. Multidetector CT, MRI, and endoscopic US help in anatomic localization of the primary tumor, local-regional spread, and metastases. Somatostatin receptor scintigraphy and fluorine 18-fluorodeoxyglucose PET/CT are helpful for functional and metabolic assessment. Knowledge of recent updates in the pathogenesis, classification, and staging of panNENs and familiarity with their imaging findings allow optimal patient treatment. ©RSNA, 2020.
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Affiliation(s)
- Lokesh Khanna
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Srinivasa R Prasad
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Abhijit Sunnapwar
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Sainath Kondapaneni
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Anil Dasyam
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Varaha S Tammisetti
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Umber Salman
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Alia Nazarullah
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
| | - Venkata S Katabathina
- From the Departments of Radiology (L.K., A.S., U.S., V.S.K.) and Pathology (V.S.T.), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229; Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, Tex (S.R.P.); Department of Molecular Biosciences, University of Texas at Austin, Austin, Tex (S.K.); Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.D.); and Department of Radiology, University of Texas Health Science Center at Houston, Houston, Tex (A.N.)
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CT-Based Radiomics Score for Distinguishing Between Grade 1 and Grade 2 Nonfunctioning Pancreatic Neuroendocrine Tumors. AJR Am J Roentgenol 2020; 215:852-863. [PMID: 32755201 DOI: 10.2214/ajr.19.22123] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
OBJECTIVE. The objective of our study was to explore the relationship between a CT-based radiomics score and grade of nonfunctioning pancreatic neuroendocrine tumors (PNETs) and to evaluate the ability of a calculated CT radiomics score to distinguish between grade 1 and grade 2 nonfunctioning PNETs. MATERIALS AND METHODS. This retrospective study assessed 102 patients with surgically resected, pathologically confirmed nonfunctioning PNETs who underwent MDCT from January 2014 to December 2017. Radiomic methods were used to extract features from portal venous phase CT scans, and the least absolute shrinkage and selection operator (LASSO) method was used to select the features. Multivariate logistic regression models were used to analyze the association between the CT radiomics score and nonfunctioning PNET grades. The performance of the CT radiomics score was assessed on the basis of its discriminative ability and clinical usefulness. RESULTS. The CT radiomics score, which consisted of four selected features, was significantly associated with nonfunctioning PNET grades. Every 1-point increase in radiomics score was associated with a 57% increased risk of grade 2 disease. The score also showed high accuracy (AUC = 0.86 for all PNETs; AUC = 0.81 for PNETs ≤ 2 cm). The best cutoff point for maximal sensitivity and specificity was a CT radiomics score of -0.134. Decision curve analysis showed that the CT radiomics score is clinically useful. CONCLUSION. The CT radiomics score shows a significant association with the grade of nonfunctioning PNETs and provides a potentially valuable noninvasive tool for distinguishing between different grades of nonfunctioning PNET, especially among patients with tumors 2 cm or smaller.
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Wang Z, Chen X, Wang J, Cui W, Ren S, Wang Z. Differentiating hypovascular pancreatic neuroendocrine tumors from pancreatic ductal adenocarcinoma based on CT texture analysis. Acta Radiol 2020; 61:595-604. [PMID: 31522519 DOI: 10.1177/0284185119875023] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Background Hypovascular pancreatic neuroendocrine tumor is usually misdiagnosed as pancreatic ductal adenocarcinoma. Purpose To investigate the value of texture analysis in differentiating hypovascular pancreatic neuroendocrine tumors from pancreatic ductal adenocarcinoma on contrast-enhanced computed tomography (CT) images. Material and Methods Twenty-one patients with hypovascular pancreatic neuroendocrine tumors and 63 patients with pancreatic ductal adenocarcinomas were included in this study. All patients underwent preoperative unenhanced and dynamic contrast-enhanced CT examinations. Two radiologists independently and manually contoured the region of interest of each lesion using texture analysis software on pancreatic parenchymal and portal phase CT images. Multivariate logistic regression analysis was performed to identify significant features to differentiate hypovascular pancreatic neuroendocrine tumors from pancreatic ductal adenocarcinomas. Receiver operating characteristic curve analysis was performed to ascertain diagnostic ability. Results The following CT texture features were obtained to differentiate hypovascular pancreatic neuroendocrine tumors from pancreatic ductal adenocarcinomas: RMS (root mean square) (odds ratio [OR] = 0.50, P<0.001), Quantile50 (OR = 1.83, P<0.001), and sumAverage (OR = 0.92, P=0.007) in parenchymal images and “contrast” in portal phase images (OR = 6.08, P<0.001). The areas under the curves were 0.76 for RMS (sensitivity = 0.75, specificity = 0.67), 0.73 for Quantile50 (sensitivity = 0.60, specificity = 0.77), 0.70 for sumAverage (sensitivity = 0.65, specificity = 0.82), 0.85 for the combined texture features (sensitivity = 0.77, specificity = 0.85). Conclusion CT texture analysis may be helpful to differentiate hypovascular pancreatic neuroendocrine tumors from pancreatic ductal adenocarcinomas. The three combined texture features showed acceptable diagnostic performance.
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Affiliation(s)
- Zhonglan Wang
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, PR China
- Department of Radiology, Nanjing Hospital of Chinese Medicine, Nanjing, Jiangsu Province, PR China
| | - Xiao Chen
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, PR China
| | - Jianhua Wang
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, PR China
| | - Wenjing Cui
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, PR China
| | - Shuai Ren
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, PR China
| | - Zhongqiu Wang
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, PR China
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Yu H, Huang Z, Li M, Wei Y, Zhang L, Yang C, Zhang Y, Song B. Differential Diagnosis of Nonhypervascular Pancreatic Neuroendocrine Neoplasms From Pancreatic Ductal Adenocarcinomas, Based on Computed Tomography Radiological Features and Texture Analysis. Acad Radiol 2020; 27:332-341. [PMID: 31495760 DOI: 10.1016/j.acra.2019.06.012] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 05/30/2019] [Accepted: 06/10/2019] [Indexed: 02/07/2023]
Abstract
RATIONALE AND OBJECTIVES To determine computed tomography (CT) radiological features and texture features that are rewarding in differentiating nonhypervascular pancreatic neuroendocrine neoplasms (PNENs) from pancreatic ductal adenocarcinomas (PDACs). MATERIALS AND METHODS We compared patients to pathologically proven nonhypervascular PNENs and age-matched controls with pathologically proven PDACs in a 1:2 ratio. Preoperative CT images in the arterial phase (AP) and portal vein phase (PVP) were obtained. Two radiologists independently reviewed the morphological characteristics of each tumor. Three-dimensional regions of interest (ROIs), drawn using ITK-SNAP software, were input into AK software (Artificial Intelligent Kit, GE) to extract texture features from AP and PVP images. Differences between PNENs and PDACs were analyzed with the chi-squared test, least absolute shrinkage and selection operator, kappa statistics, and uni- and multivariate logistic regression analyses. RESULTS In total, 40 nonhypervascular PNENs and 80 PDACs were evaluated. Maximum diameter on axial section, margin, calcification, vascularity in the tumor, and tumor heterogeneity were significantly different between PDACs and nonhypervascular PNENs. Multivariate analysis showed well-defined tumor margin (odds ratio: 21.0) and presence of calcification (odds ratio: 4.4) were significant predictors of nonhypervascular PNENs. The area under the receiver operating characteristic curve of the radiological feature model, AP texture model, and PVP texture model were 0.780, 0.855, and 0.929, respectively, based on logistic regression. CONCLUSION A well-defined margin and calcification in the tumor were helpful in discriminating nonhypervascular PNENs from PDACs. Texture analysis of contrast-enhanced CT images could be beneficial in differentially diagnosing nonhypervascular PNENs and PDACs.
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Affiliation(s)
- Haopeng Yu
- Department of Radiology, West China Hospital of Sichuan University, Guoxue Lane 37#, Chengdu 610041, PR China
| | - Zixing Huang
- Department of Radiology, West China Hospital of Sichuan University, Guoxue Lane 37#, Chengdu 610041, PR China
| | - Mou Li
- Department of Radiology, West China Hospital of Sichuan University, Guoxue Lane 37#, Chengdu 610041, PR China
| | - Yi Wei
- Department of Radiology, West China Hospital of Sichuan University, Guoxue Lane 37#, Chengdu 610041, PR China
| | - Lin Zhang
- Department of Radiology, West China Hospital of Sichuan University, Guoxue Lane 37#, Chengdu 610041, PR China
| | - Chengmin Yang
- Department of Radiology, West China Hospital of Sichuan University, Guoxue Lane 37#, Chengdu 610041, PR China
| | - Yongchang Zhang
- Department of Radiology, West China Hospital of Sichuan University, Guoxue Lane 37#, Chengdu 610041, PR China
| | - Bin Song
- Department of Radiology, West China Hospital of Sichuan University, Guoxue Lane 37#, Chengdu 610041, PR China.
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Yang B, Chen HY, Zhang XY, Pan Y, Lu YF, Yu RS. The prognostic value of multidetector CT features in predicting overall survival outcomes in patients with pancreatic neuroendocrine tumors. Eur J Radiol 2020; 124:108847. [PMID: 31991300 DOI: 10.1016/j.ejrad.2020.108847] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 12/03/2019] [Accepted: 01/18/2020] [Indexed: 12/14/2022]
Abstract
PURPOSE To assess the prognostic value of multidetector CT in predicting overall survival outcomes in patients with pancreatic neuroendocrine tumors (PNETs). METHOD Seventy-one patients pathologically diagnosed with PNETs were retrospectively included. The clinical and imaging information was evaluated by two radiologists. The difference between well-differentiated and poorly differentiated PNETs was analyzed. Cox proportional hazards models were created to determine the risk factors for overall survival. Kaplan-Meier survival analyses with log-rank tests were used among different subgroups of patients with PNETs. RESULTS In the whole cohort, the median survival was 36 months, and the 5-year survival rate was 84.8 %. Patients with poorly differentiated PNETs were more likely to present with symptoms, abnormal tumor markers, larger diameters, irregular shapes, ill-defined margins, invasion into nearby tissues, liver and lymph node metastases, and lower enhancement ratio than those with well-differentiated PNETs (P < 0.05). In the multivariate analysis, lymph node metastases (hazard ratio: 21.52, P = 0.009) and a portal enhancement ratio less than 1.02 (hazard ratio: 30.89, P = 0.024) were significant factors for overall survival. Overall survival decreased with an ill-defined margin, irregular shape, poor differentiation, grade 3 disease, nonfunctional status, abnormal tumor marker levels, invasion into nearby tissues, lymph node and liver metastases, and lower enhancement ratio (log-rank P < 0.05). CONCLUSIONS Poorly differentiated PNETs were more aggressiveness than well-differentiated PNETs. Lymph node metastases and a portal enhancement ratio < 1.02 were independent prognostic factors for worse overall survival outcomes in patients with PNETs.
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Affiliation(s)
- Bo Yang
- Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Radiology, Zhejiang Prison Center Hospital (Zhejiang Youth Hospital), Hangzhou, China
| | - Hai-Yan Chen
- Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xue-Yan Zhang
- Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Radiology, Institute of Occupational Diseases, Zhejiang Academy of Medical Sciences, Hangzhou, China
| | - Yao Pan
- Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yuan-Fei Lu
- Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ri-Sheng Yu
- Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
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Ma W, Wei M, Han Z, Tang Y, Pan Q, Zhang G, Ren J, Huan Y, Li N. The added value of intravoxel incoherent motion diffusion weighted imaging parameters in differentiating high-grade pancreatic neuroendocrine neoplasms from pancreatic ductal adenocarcinoma. Oncol Lett 2019; 18:5448-5458. [PMID: 31612053 PMCID: PMC6781772 DOI: 10.3892/ol.2019.10863] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2018] [Accepted: 08/16/2019] [Indexed: 12/13/2022] Open
Abstract
The aim of the present study was to investigate the potential significance of intravoxel incoherent motion (IVIM)-diffusion weighted imaging (DWI) in differentiating high-grade pancreatic neuroendocrine neoplasms (pNENs) from pancreatic ductal adenocarcinoma (PDAC). A total of 50 patients, including 37 patients with PDAC and 13 patients with high-grade pNENs, underwent pancreatic multiple b-values DWI with 15 b-values including 0, 10, 20, 40, 60, 80, 100, 150, 200, 400, 800, 1,000, 1,200, 1,500 and 2,000 sec/mm2. Standard apparent diffusion coefficient (ADCstandard) and IVIM parameter [slow apparent diffusion coefficient (Dslow), fast apparent diffusion coefficient (Dfast), fraction of fast apparent diffusion coefficient (ƒ)] values of PDAC and pNENs were compared. P<0.05 was considered to indicate a statistically significant difference. Receiver operating characteristics analysis was performed in order to evaluate the diagnostic potential of IVIM parameters for differentiating high-grade pNENs from PDAC. Dslow of pNENs was significantly lower compared with that of PDAC (0.460 vs. 0.579×10−3 mm2/sec; P=0.001). Dfast of pNENs was significantly higher compared with that of PDAC (13.361 vs. 4.985×10−3 mm2/sec; P<0.001). Area under the curve of Dslow, Dfast and combined Dslow and Dfast was 0.793, 0.863 and 0.885 respectively. The specificity and sensitivity of Dslow≤0.472×10−3 mm2/sec were 97.3 and 53.9%, respectively, for differentiating high-grade pNENs from PDAC. The specificity and sensitivity of Dfast >9.58×10−3 mm2/sec were 91.9 and 69.2%, respectively, for differentiating high-grade pNENs from PDAC. When Dslow and Dfast were combined, the specificity and sensitivity for differentiating high-grade pNENs from PDAC were 76.9 and 100%, respectively. Taken together, these results indicated that the diffusion-associated parameter Dslow and the perfusion-associated parameter Dfast of IVIM-DWI may differentiate high-grade pNENs from PDAC with high diagnostic accuracy, and that IVIM-DWI may be a valuable biomarker in differentiating pancreatic neoplasms.
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Affiliation(s)
- Wanling Ma
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Mengqi Wei
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Zhiwei Han
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Yongqiang Tang
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Qi Pan
- Department of Radiology, Second Affiliated Hospital of Xi'an Medical Collage, Xi'an, Shaanxi 710038, P.R. China
| | - Guangwen Zhang
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Jing Ren
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Yi Huan
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
| | - Na Li
- Department of Radiology, Ninth Hospital of Xi'an City, Xi'an, Shaanxi 710068, P.R. China
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Evaluating radiological response in pancreatic neuroendocrine tumours treated with sunitinib: comparison of Choi versus RECIST criteria (CRIPNET_ GETNE1504 study). Br J Cancer 2019; 121:537-544. [PMID: 31477779 PMCID: PMC6889276 DOI: 10.1038/s41416-019-0558-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Accepted: 08/09/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND The purpose of our study was to analyse the usefulness of Choi criteria versus RECIST in patients with pancreatic neuroendocrine tumours (PanNETs) treated with sunitinib. METHOD A multicentre, prospective study was conducted in 10 Spanish centres. Computed tomographies, at least every 6 months, were centrally evaluated until tumour progression. RESULTS One hundred and seven patients were included. Median progression-free survival (PFS) by RECIST and Choi were 11.42 (95% confidence interval [CI], 9.7-15.9) and 15.8 months (95% CI, 13.9-25.7). PFS by Choi (Kendall's τ = 0.72) exhibited greater correlation with overall survival (OS) than PFS by RECIST (Kendall's τ = 0.43). RECIST incorrectly estimated prognosis in 49.6%. Partial response rate increased from 12.8% to 47.4% with Choi criteria. Twenty-four percent of patients with progressive disease according to Choi had stable disease as per RECIST, overestimating treatment effect. Choi criteria predicted PFS/OS. Changes in attenuation occurred early and accounted for 21% of the variations in tumour volume. Attenuation and tumour growth rate (TGR) were associated with improved survival. CONCLUSION Choi criteria were able to capture sunitinib's activity in a clinically significant manner better than RECIST; their implementation in standard clinical practice shall be strongly considered in PanNET patients treated with this drug.
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Sato-Dahlman M, Yamamoto M. The Development of Oncolytic Adenovirus Therapy in the Past and Future - For the Case of Pancreatic Cancer. Curr Cancer Drug Targets 2019; 18:153-161. [PMID: 28228084 DOI: 10.2174/1568009617666170222123925] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Revised: 11/15/2016] [Accepted: 12/05/2016] [Indexed: 12/16/2022]
Abstract
Pancreatic cancer is an aggressive malignant disease and the efficacy of current treatments for unresectable diseases is quite limited despite recent advances. Gene therapy /virotherapy strategies may provide new options for the treatment of various cancers including pancreatic cancer. Oncolytic adenovirus shows an antitumoral effect via its intratumoral amplification and strong cytocidal effect in a variety of cancers and it has been employed for the development of potent oncolytic virotherapy agents for pancreatic cancer. Our ultimate goal is to develop an oncolytic adenovirus enabling the treatment of patients with advanced or spread diseases by systemic injection. Systemic application of oncolytic therapy mandates more efficient and selective gene delivery and needs to embody sufficient antitumor effect even with limited initial delivery to the tumor location. In this review, the current status of oncolytic adenoviruses from the viewpoints of vector design and potential strategies to overcome current obstacles for its clinical application will be described. We will also discuss the efforts to improve the antitumor activity of oncolytic adenovirus, in in vivo animal models, and the combination therapy of oncolytic adenovirus with radiation and chemotherapy.
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Affiliation(s)
- Mizuho Sato-Dahlman
- Division of Basic and Translational Medicine, Department of Surgery, University of Minnesota, MN, United States
| | - Masato Yamamoto
- Division of Basic and Translational Medicine, Department of Surgery, University of Minnesota, MN, United States
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Pancreatic neuroendocrine tumors: MR imaging features preoperatively predict lymph node metastasis. Abdom Radiol (NY) 2019; 44:1000-1009. [PMID: 30539251 DOI: 10.1007/s00261-018-1863-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSES Predictive factors of lymph node metastasis (LNM) in pancreatic neuroendocrine tumors (pNETs) are not well established. We sought to identify the value of MR imaging features in preoperatively predicting the lymph node metastasis of pNETs. MATERIALS AND METHODS In this study, we enrolled 108 consecutive patients with pNETs between January 2009 and June 2018. MR morphologic features and quantitative data were evaluated. Predictors of LNM were evaluated using univariate and multivariate logistic regression models. RESULTS A total of 108 patients with pNETs were finally enrolled, including 82 LNM-negative and 26 LNM-positive patients. Features significantly related to the LNM of pNETs at univariate analysis were tumor size > 2 cm (P = 0.003), Ki-67 > 5% (P = 0.002), non-enhancement pattern (P < 0.001), apparent diffusion coefficient value (P < 0.001), main pancreatic duct dilation (P < 0.001) and pancreatic atrophy (P = 0.032) and extrapancreatic tumor spread (P = 0.001), CNRs during arterial, portal and delay phase (P = 0.005, 0.047, and 0.045, respectively), and histological classification (P = 0.006). At multivariate analysis, non-enhancement pattern (P = 0.019; odds ratio, 6.652; 95% CI 1.369, 32.321) and main pancreatic duct dilation (P = 0.018; odds ratio, 6.745; 95% CI 1.379, 32.991) were independent risk factors for predicting the LNM of pNETs. CONCLUSION The non-enhancement characteristic and main pancreatic duct dilation appear to be linked with LNM in pNETs. These radiological predictors can be easily obtained preoperatively, and may help to avoid missing pNETs with a high risk of LNM.
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Sun HT, Zhang SL, Liu K, Zhou JJ, Wang XX, Shen TT, Song XH, Guo YL, Wang XL. MRI-based nomogram estimates the risk of recurrence of primary nonmetastatic pancreatic neuroendocrine tumors after curative resection. J Magn Reson Imaging 2018; 50:397-409. [PMID: 30589158 DOI: 10.1002/jmri.26603] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Revised: 11/26/2018] [Accepted: 11/26/2018] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Accurate estimation of the recurrence of pancreatic neuroendocrine tumors help with prognosis, guide follow-up, and avoid futile treatments. PURPOSE To investigate whether MRI features could preoperatively estimate the recurrence of pancreatic neuroendocrine tumors (PNETs) and to refine a novel prognostic model through developing a nomogram incorporating various MRI features. STUDY TYPE Retrospective. POPULATION In all, 81 patients with clinicopathologically confirmed nonmetastatic PNETs. FIELD STRENGTH/SEQUENCES 1.5 T MR, including T1 -weighted, T2 -weighted, and diffusion-weighted imaging sequences. ASSESSMENT Qualitative and quantitative MRI features of PNET were assessed by three experienced radiologists. STATISTICAL TESTS Uni- and multivariable analyses for recurrence-free survival (RFS) were evaluated using a Cox proportional hazards model. The MRI-based nomogram was then designed based on multivariable logistic analysis in our study and the performance of the nomogram was validated according to C-index, calibration, and decision curve analyses. RESULTS MRI features, including tumor size (hazard ratio [HR]: 14.131; P = 0.034), enhancement pattern (HR: 21.821, P = 0.032), and the apparent diffusion coefficient (ADC) values (HR: 0.055, P = 0.038) were significant independent predictors of RFS at multivariable analysis. The performance of the nomogram incorporating various MRI features (with a C-index of 0.910) was improved compared with that based on tumor size, enhancement pattern, and ADC alone (with C-index values of 0.672, 0.851, and 0.809, respectively). The calibration curve of the nomogram exhibited perfect consistency between estimation and observation at 0.5, 1, and 2 years after surgery. The decision curve showed that a nomogram incorporating three features had more favorable clinical predictive usefulness than any single feature. DATA CONCLUSION MRI features can be considered effective recurrence predictors for PNETs after surgery. The preliminary nomogram incorporating various MRI features could assess the risk of recurrence in PNETs and may be used to optimize individual treatment strategies. LEVEL OF EVIDENCE 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:397-409.
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Affiliation(s)
- Hai-Tao Sun
- Shanghai Institute of Medical Imaging, Shanghai, China.,Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Shi-Long Zhang
- Institute of Fudan-Minhang Academic Health System, Minhang Branch, Zhongshan hospital, Fudan University, Shanghai, China
| | - Kai Liu
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jian-Jun Zhou
- Shanghai Institute of Medical Imaging, Shanghai, China.,Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xing-Xing Wang
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ting-Ting Shen
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xu-Hao Song
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ying-Long Guo
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiao-Lin Wang
- Shanghai Institute of Medical Imaging, Shanghai, China.,Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
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McGovern JM, Singhi AD, Borhani AA, Furlan A, McGrath KM, Zeh HJ, Bahary N, Dasyam AK. CT Radiogenomic Characterization of the Alternative Lengthening of Telomeres Phenotype in Pancreatic Neuroendocrine Tumors. AJR Am J Roentgenol 2018; 211:1020-1025. [PMID: 30160983 DOI: 10.2214/ajr.17.19490] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
OBJECTIVE The objective of this study was to identify imaging characteristics in patients with known pancreatic neuroendocrine tumors (PanNETs) that predict the alternative lengthening of telomeres (ALT) phenotype by blinded retrospective review of preoperative multiphasic CT scans. MATERIALS AND METHODS For this retrospective study of 121 preoperative CT examinations of patients with resected PanNETs, two radiologists independently reviewed the CT examinations for tumor characteristics including size, shape, cystic or necrotic elements, calcifications, invasion of adjacent organs and vessels, biliary duct dilatation, pancreatic duct dilatation, and hepatic metastases. Univariate analysis of association of CT characteristics with ALT phenotype was performed with Fisher exact tests or t tests, and multivariate analysis was assessed by multiple logistic regression. RESULTS Univariate analysis showed that the following CT features were significantly associated with the ALT phenotype: lobulated or irregular tumor shape (p = 0.001), tumor necrosis (p = 0.002), vascular invasion (p < 0.001), pancreatic duct dilatation (p < 0.001), and hepatic metastasis (p < 0.001). Multivariate analysis found that the combination of pancreatic duct dilatation, hepatic metastasis, and size of tumor ≥ 3 cm was a strong predictor of ALT phenotype (odds ratio = 20.3; 95% CI = 2.3-176.3; AUC = 0.58; p = 0.006). CONCLUSION This study showed that several preoperative CT features of PanNETs are associated with the ALT phenotype, which is known to predict poor prognosis. Additionally, CT findings of intratumoral calcifications and metastases predicted poor survival independent of the ALT status.
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Affiliation(s)
- Jonathan M McGovern
- 1 Department of Radiology, Division of Abdominal Imaging, University of Pittsburgh Medical Center, 200 Lothrop St, E Wing E2051B, Ste 200, Pittsburgh, PA 15213
| | - Aatur D Singhi
- 2 Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Amir A Borhani
- 1 Department of Radiology, Division of Abdominal Imaging, University of Pittsburgh Medical Center, 200 Lothrop St, E Wing E2051B, Ste 200, Pittsburgh, PA 15213
| | - Alessandro Furlan
- 1 Department of Radiology, Division of Abdominal Imaging, University of Pittsburgh Medical Center, 200 Lothrop St, E Wing E2051B, Ste 200, Pittsburgh, PA 15213
| | - Kevin M McGrath
- 3 Department of Internal Medicine, Division of Gastroenterology, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Herbert J Zeh
- 4 Department of Surgery, UT Southwestern Medical Center, Dallas, TX
| | - Nathan Bahary
- 5 Department of Internal Medicine, Division of Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Anil K Dasyam
- 1 Department of Radiology, Division of Abdominal Imaging, University of Pittsburgh Medical Center, 200 Lothrop St, E Wing E2051B, Ste 200, Pittsburgh, PA 15213
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Grillo F, Florio T, Ferraù F, Kara E, Fanciulli G, Faggiano A, Colao A. Emerging multitarget tyrosine kinase inhibitors in the treatment of neuroendocrine neoplasms. Endocr Relat Cancer 2018; 25:R453-R466. [PMID: 29769293 DOI: 10.1530/erc-17-0531] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Accepted: 05/16/2018] [Indexed: 12/18/2022]
Abstract
In the last few years, the therapeutic approach for neuroendocrine neoplasms (NENs) has changed dramatically following the approval of several novel targeted treatments. The multitarget tyrosine kinase inhibitor (MTKI), sunitinib malate, has been approved by Regulatory Agencies in pancreatic NENs. The MTKI class, however, includes several other molecules (approved for other conditions), which are currently being studied in NENs. An in-depth review on the studies published on the MTKIs in neuroendocrine tumors such as axitinib, cabozantinib, famitinib, lenvatinib, nintedanib, pazopanib, sorafenib and sulfatinib was performed. Furthermore, we extensively searched on the Clinical Trial Registries databases worldwide, in order to collect information on the ongoing clinical trials related to this topic. Our systematic analysis on emerging MTKIs in the treatment of gastroenteropancreatic and lung NENs identifies in vitro and in vivo studies, which demonstrate anti-tumor activity of diverse MTKIs on neuroendocrine cells and tumors. Moreover, for the first time in the literature, we report an updated view concerning the upcoming clinical trials in this field: presently, phase I, II and III clinical trials are ongoing and will include, overall, a staggering 1667 patients. This fervid activity underlines the increasing interest of the scientific community in the use of emerging MTKIs in NEN treatment.
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Affiliation(s)
- Federica Grillo
- Pathology UnitDepartment of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova, Genova, Italy
- Ospedale Policlinico San Martino IRCCSGenova, Italy
| | - Tullio Florio
- Pharmacology UnitDepartment of Internal Medicine (DIMI), University of Genova, Genova, Italy
| | - Francesco Ferraù
- Department of Human Pathology of Adulthood and ChildhoodUniversity of Messina, Messina, Italy
| | - Elda Kara
- Unit of EndocrinologyMetabolism, Diabetology and Nutrition, Azienda Sanitaria Universitaria Integrata di Udine, Ospedale Santa Maria della Misericordia, Udine, Italy
| | - Giuseppe Fanciulli
- Neuroendocrine Tumours UnitDepartment of Clinical and Experimental Medicine, University of Sassari - AOU Sassari, Sassari, Italy
| | - Antongiulio Faggiano
- Department of Clinical Medicine and SurgeryUniversity 'Federico II', Naples, Italy
| | - Annamaria Colao
- Department of Clinical Medicine and SurgeryUniversity 'Federico II', Naples, Italy
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Karmazanovsky G, Belousova E, Schima W, Glotov A, Kalinin D, Kriger A. Nonhypervascular pancreatic neuroendocrine tumors: Spectrum of MDCT imaging findings and differentiation from pancreatic ductal adenocarcinoma. Eur J Radiol 2018; 110:66-73. [PMID: 30599875 DOI: 10.1016/j.ejrad.2018.04.006] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Revised: 02/08/2018] [Accepted: 04/05/2018] [Indexed: 12/20/2022]
Abstract
PURPOSE The purpose of our study was to determine contrast-enhanced MDCT features to differentiate nonhypervascular pancreatic neuroendocrine tumors (PNETs) from pancreatic ductal adenocarcinomas (PDACs). METHODS and materials: We included 74 patients with PNETs and 80 patients with PDACs who underwent preoperative MDCT. Two radiologists evaluated the morphologic characteristic and enhancement patterns of the tumors. Quantitative and qualitative analysis was performed, including evaluation of tumor size, homogeneity, contrast enhancement pattern, presence of pancreatic duct dilatation and tumor invasion to the adjacent vessels and peripancreatic infiltration. Tumor-to-pancreas enhancement ratio was defined as the Hounsfield units (HU) value of the tumor divided by the HU value of the pancreas. the first group was hypervascular PNETs showing hyperenhancement on arterial phase images and nonhypervascular PNETs, showing iso- or hypoenhancement on arterial phase images. After that, two radiologists estimated the possibilities of PNET or PDAC were for nonhypervascular PNETs. RESULTS On the basis of arterial enhancement, 43 PNETs were hypervascular and 31 were nonhypervascular. When compared to PDAC, nonhypervascular PNETs more frequently had well-defined tumor margins, intratumoral cystic components, calcifications and blood vessels and less frequently had main pancreatic duct dilatation, peripancreatic infiltration and vascular invasion (p < 0.01 for all). Nonhypervascular PNETs had higher tumor-to-pancreas enhancement ratio in venous phase (1.02 vs. 0.78, p = 0.012). Nonhypervascular PNETs more often had portal-venous hyperenhancement or persistent isoenhancement, while PDAC more often had persistent hypoenhancement or gradual delayed enhancement (p < 0.001). The absence of pancreatic duct dilatation and portal-venous hyperenhancement or persistent isoenhancement were the independent predictors for nonhypervascular PNETs. (The most accurate MDCT-findings to predict nonhypervascular PNET were the absence of pancreatic duct dilatation and peripancreatic infiltration (79% and 92% accuracy), portal-venous phase hyperenhancement or persistent isoenhancement (77%), the presence of intratumoral blood vessels (77%) and relative enhancement intensity in venous phase >0.9 (76%). Using these criteria, the area under curve for differentiation of PNET from PDAC was 0.906-0.846. CONCLUSION Combined assessment of the enhancement and morphologic characteristics can improve the differentiation between nonhypervascular PNETs and PDAC at contrast-enhanced MDCT.
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Affiliation(s)
- Grigory Karmazanovsky
- Department of Radiology, A.V. Vishnevsky Institute of Surgery, Moscow, Russia; Department of Radiology, Faculty of Postgraduate Professional Training of Physicians, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
| | - Elena Belousova
- Department of Radiology, A.V. Vishnevsky Institute of Surgery, Moscow, Russia; Department of Radiology, Faculty of Postgraduate Professional Training of Physicians, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
| | - Wolfgang Schima
- Department of Diagnostic and Interventional Radiology, Goettlicher Heiland Krankenhaus, Barmherzige Schwestern Krankenhaus, and Sankt Josef Krankenhaus, Vinzenzgruppe, Vienna, Austria
| | - Andrei Glotov
- Department of Pathology, A.V. Vishnevsky Institute of Surgery, Moscow, Russia
| | - Dmitry Kalinin
- Department of Pathology, A.V. Vishnevsky Institute of Surgery, Moscow, Russia
| | - Andrei Kriger
- Department of Abdominal Surgery, A.V. Vishnevsky Institute of Surgery, Moscow, Russia
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Sato-Dahlman M, Wirth K, Yamamoto M. Role of Gene Therapy in Pancreatic Cancer-A Review. Cancers (Basel) 2018; 10:E103. [PMID: 29614005 PMCID: PMC5923358 DOI: 10.3390/cancers10040103] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2018] [Revised: 03/27/2018] [Accepted: 03/30/2018] [Indexed: 01/05/2023] Open
Abstract
Mortality from pancreatic ductal adenocarcinoma (PDAC) has remained essentially unchanged for decades and its relative contribution to overall cancer death is projected to only increase in the coming years. Current treatment for PDAC includes aggressive chemotherapy and surgical resection in a limited number of patients, with median survival of optimal treatment rather dismal. Recent advances in gene therapies offer novel opportunities for treatment, even in those with locally advanced disease. In this review, we summarize emerging techniques to the design and administration of virotherapy, synthetic vectors, and gene-editing technology. Despite these promising advances, shortcomings continue to exist and here will also be highlighted those approaches to overcoming obstacles in current laboratory and clinical research.
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Affiliation(s)
| | - Keith Wirth
- Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
| | - Masato Yamamoto
- Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
- Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA.
- Surgery BTR, MMC 195, 8195F, 420 Delaware St SE, Minneapolis, MN 55455, USA.
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Choi TW, Kim JH, Yu MH, Park SJ, Han JK. Pancreatic neuroendocrine tumor: prediction of the tumor grade using CT findings and computerized texture analysis. Acta Radiol 2018; 59:383-392. [PMID: 28766979 DOI: 10.1177/0284185117725367] [Citation(s) in RCA: 86] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Background Pancreatic neuroendocrine tumors (PNET) include heterogeneous tumors with a variable degree of inherent biologic aggressiveness represented by the histopathologic grade. Although several studies investigated the computed tomography (CT) characteristics which can predict the histopathologic grade of PNET, accurate prediction of the PNET grade by CT examination alone is still limited. Purpose To investigate the important CT findings and CT texture variables for prediction of grade of PNET. Material and Methods Sixty-six patients with pathologically confirmed PNETs (grade 1 = 45, grades 2/3 = 21) underwent preoperative contrast-enhanced CT. Two reviewers determined the presence of predefined CT findings. CT texture was also analyzed on arterial and portal phase using both two-dimensional (2D) and three-dimensional (3D) analysis. Multivariate logistic regression analysis was performed in order to identify significant predictors for tumor grade. Results Among CT findings and CT texture variables, the significant predictors for grade 2/3 tumors were an ill-defined margin (odds ratio [OR] = 7.273), lower sphericity (OR = 0.409) on arterial 2D analysis, higher skewness (OR = 1.972) and lower sphericity (OR = 0.408) on arterial 3D analysis, lower kurtosis (OR = 0.436) and lower sphericity (OR = 0.420) on portal 2D analysis, and a larger surface area (OR = 2.007) and lower sphericity (OR = 0.503) on portal 3D analysis ( P < 0.05). Diagnostic performance of texture analysis was superior to CT findings (AUC = 0.774 vs. 0.683). Conclusion CT is useful for predicting grade 2/3 PNET using not only the imaging findings including an ill-defined margin, but also the CT texture variables such as lower sphericity, higher skewness, and lower kurtosis.
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Affiliation(s)
- Tae Won Choi
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jung Hoon Kim
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea
- Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Mi Hye Yu
- Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - Sang Joon Park
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea
- Cancer Research Institute, Seoul National University, Seoul, Republic of Korea
| | - Joon Koo Han
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea
- Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
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Cui Y, Li X, Gao S, Li Z, Li Y, Lu M, Sun Y. Utility of CT in differentiating liver metastases of well-differentiated gastroenteropancreatic neuroendocrine neoplasms from poorly-differentiated neuroendocrine neoplasms. Chin J Cancer Res 2018; 30:31-39. [PMID: 29545717 DOI: 10.21147/j.issn.1000-9604.2018.01.04] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Objective To determine the capability of dynamic enhanced computed tomography (CT) to differentiate liver metastases (LMs) of well-differentiated from poorly-differentiated gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Methods Patients with LMs of GEP-NENs who underwent dynamic enhanced CT examination in Peking University Cancer Hospital from January 2009 to October 2015 were included and data were retrospectively analyzed. We assessed the qualitative and quantitative CT features to identify the significant differentiating CT features of LMs of poorly-differentiated GEP-NENs from those of well-differentiated GEP-NENs using univariate analysis and a multivariate logistic regression model. Results The study included 22 patients with LMs of well-differentiated GEP-NENs and 32 patients with LMs of poorly-differentiated GEP-NENs. Univariate analysis revealed statistically significant differences between the LMs of well- and poorly-differentiated GEP-NENs in terms of feeding arteries (36.4% vs. 75.0%, χ2=8.061, P=0.005), intratumoral neovascularity (18.2% vs. 59.4%, χ2=9.047, P=0.003), lymphadenopathy (27.3% vs. 81.2%, χ2=15.733, P<0.001), tumor-to-aortic ratio in the hepatic arterial and portal venous phase (T-A/AP: 0.297±0.080vs. 0.251±0.059, t=2.437, P=0.018; T-A/PVP: 0.639±0.138 vs. 0.529±0.117, t=3.163, P=0.003) and tumor-to-liver ratio in the hepatic arterial phase (T-L/AP: 1.108±0.267 vs. 0.907±0.240, t=2.882, P=0.006). The LMs of poorly-differentiated GEP-NENs showed more feeding arteries, more intratumoral neovascularity, more lymphadenopathy and a lower tumor-to-aortic ratio. Multivariate analysis suggested that intratumoral neovascularity [P=0.015, OR=0.108, 95% confidence interval (95% CI), 0.018-0.646], lymphadenopathy (P=0.001, OR=0.055, 95% CI, 0.009-0.323) and T-A/PVP (P=0.004, OR=5.3E-5, 95% CI, 0.000-0.044) were independent factors for differentiating LMs of poorly-differentiated from well-differentiated GEP-NENs. Conclusions Dynamic enhanced CT features (intratumoral neovascularity, lymphadenopathy and T-A/PVP) are useful in the pathological classification of LMs of GEP-NENs.
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Affiliation(s)
- Yong Cui
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), 1Department of Radiology
| | - Xiaoting Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), 1Department of Radiology
| | - Shunyu Gao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), 1Department of Radiology
| | - Zhongwu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), 1Department of Radiology
| | - Yanling Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), 1Department of Radiology
| | - Ming Lu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), 1Department of Radiology
| | - Yingshi Sun
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), 1Department of Radiology
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Kang J, Ryu JK, Son JH, Lee JW, Choi JH, Lee SH, Kim YT. Association between pathologic grade and multiphase computed tomography enhancement in pancreatic neuroendocrine neoplasm. J Gastroenterol Hepatol 2018; 33:1677-1682. [PMID: 29514405 DOI: 10.1111/jgh.14139] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Revised: 02/06/2018] [Accepted: 03/01/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIM Pancreatic neuroendocrine neoplasms (PanNENs) are rare diseases but gradually increasing in prevalence with different prognosis. Multiphase contrast-enhanced computed tomography (CT) is known as widely used imaging modality for the diagnosis of pancreatic tumors. We aimed to investigate whether CT enhancement pattern is associated with the pathologic tumor grade and can predict that of PanNEN. METHODS Ninety PanNEN patients who underwent multiphase enhanced CT before pathologic diagnosis were retrospectively reviewed. CT enhancement values at each phase were measured, and its relation with pathologic grade was assessed. RESULTS Ninety PanNENs included 62 G1 (68.9%), 21 G2 (23.3%), and 7 G3 (7.8%). The enhancement values of the early arterial phase were significantly different among three groups (G1 119.4 HU, G2 94.7 HU, and G3 64.8 HU; G1 vs G2, P = 0.043; G1 vs G3, P = 0.001; and G2 vs G3, P = 0.027). In the late arterial phase, there was a difference between grade 1/2 and 3 but no significant difference between grade 1 and grade 2 (G1 164.3 HU, G2 142.9 HU, and G3 94.1 HU; G1 vs G2, P = 0.804; G1 vs G3, P = 0.016; and G2 vs G3, P = 0.022). The enhancement value of the portal phase did not differ significantly among the three groups. Diagnostic ability of the early arterial enhancement value for the differentiation of the G1 (cutoff 109.5 HU, sensitivity 73.3%, and specificity 62.5%) was comparable with that of the tumor size (cutoff 20.5 mm, sensitivity 68.9%, and specificity 66.7%). CONCLUSIONS Computed tomography enhancement value at early arterial phase and its changing pattern can be a useful predictor for the differentiation of pathologic grade of PanNENs.
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Affiliation(s)
- Jinwoo Kang
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Ji Kon Ryu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jun Hyuk Son
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Woo Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jin Ho Choi
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Sang Hyub Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Yong-Tae Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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