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Ye X, Hua H, Hu C, Dai J, Wu C, Huai J, Shen Z. Endoscopic Ultrasound-Guided Fine Needle Acquisition for Evaluation of Pancreatic Neuroendocrine Tumors: A Meta-Analysis. J Clin Gastroenterol 2025; 59:310-320. [PMID: 39312536 DOI: 10.1097/mcg.0000000000002070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Accepted: 08/05/2024] [Indexed: 09/25/2024]
Abstract
AIMS The aim of this meta-analysis was to assess the diagnostic performance of EUS-FNA/B in patients with panNETs. METHODS We conducted a computerized search of the MEDLINE and Embase databases to identify relevant articles. The primary outcomes involved grading concordance rate, diagnostic rate, and correlation coefficient (Cohen's κ) for FNA/B samples compared with surgical specimens. Secondary outcomes included sample adequacy, mean number of passes, and adverse events. RESULTS Forty-five studies involving 2978 patients were finally included. The pooled concordance rate between EUS-FNA/B and surgical grading was 0.77 (95% CI: 0.73-0.80; I2 =48.2%). A significantly higher level of concordance was observed in G1 subgroup (0.88, 95% CI: 0.84-0.91), whereas the G2 subgroup revealed the lowest level of agreement (0.59, 95% CI: 0.52-0.65; P < 0.001). Pooled diagnostic rate for FNA/B sampling was 0.83 (95% CI: 0.79-0.86; I2 =63.3%). In addition, FNB outperformed FNA in terms of sample adequacy (0.93 for FNB vs. 0.81 for FNA; P =0.007) and number of needle passes required (2.53 for FNB vs. 3.32 for FNA; P =0.013). Moreover, the overall level of agreement for grading was moderate (κ=0.59, 95% CI: 0.49-0.68; I2 =84.5%). There were a limited number of adverse events that had minor influence on patient outcomes (0.03, 95% CI: 0.02-0.05; I2 =19.2%). CONCLUSIONS EUS-FNA/B is a reliable approach for the diagnosis and preoperative grading of panNET, with FNB demonstrating superior performance compared with FNA.
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Affiliation(s)
- Xiaohua Ye
- Department of Gastroenterology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou
- Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua
| | - Hongjun Hua
- Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua
| | - Chunxiao Hu
- Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua
| | - Jianying Dai
- Department of Research and Development, Hangzhou Yingjian Bioscience and technology Co., Ltd
| | - Chenjiao Wu
- Department of Gastroenterology, Digestive Endoscopy Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou
| | - Jiaping Huai
- Department of Critical Care, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China
| | - Zhe Shen
- Department of Gastroenterology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou
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Elkelany OO, Karaisz FG, Davies B, Krishna SG. An Overview of Pancreatic Neuroendocrine Tumors and an Update on Endoscopic Techniques for Their Management. Curr Oncol 2023; 30:7566-7580. [PMID: 37623030 PMCID: PMC10453483 DOI: 10.3390/curroncol30080549] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 07/25/2023] [Accepted: 07/31/2023] [Indexed: 08/26/2023] Open
Abstract
The growing importance of advanced endoscopy in the diagnosis and treatment of pancreatic neuroendocrine neoplasms (PanNETs) necessitates a comprehensive understanding of various biochemical markers, genetic testing methods, radiological techniques, and treatment approaches that encompass multiple disciplines within and beyond gastrointestinal oncology. This review aims to highlight key aspects of these topics, with a specific focus on emerging EUS-guided procedures for the management of PanNETs.
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Affiliation(s)
- Osama O. Elkelany
- Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Fred G. Karaisz
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Benjamin Davies
- College of Medicine, The Ohio State University, Columbus, OH 43201, USA
| | - Somashekar G. Krishna
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
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Franchellucci G, Andreozzi M, Carrara S, De Luca L, Auriemma F, Paduano D, Calabrese F, Facciorusso A, Poletti V, Zerbi A, Lania AG, Bertuzzi AF, Spaggiari P, Pedicini V, Rodari M, Fusaroli P, Lisotti A, Ofosu A, Repici A, Mangiavillano B. Contrast Enhanced EUS for Predicting Solid Pancreatic Neuroendocrine Tumor Grade and Aggressiveness. Diagnostics (Basel) 2023; 13:239. [PMID: 36673049 PMCID: PMC9857765 DOI: 10.3390/diagnostics13020239] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 12/29/2022] [Accepted: 12/29/2022] [Indexed: 01/11/2023] Open
Abstract
Pancreatic neuroendocrine tumor (PNET) behavior assessment is a daily challenge for physicians. Modern PNET management varies from a watch-and-wait strategy to surgery depending on tumor aggressiveness. Therefore, the aggressiveness definition plays a pivotal role in the PNET work-up. The aggressiveness of PNETs is mainly based on the dimensions and histological grading, with sometimes a lack of specificity and sensibility. In the last twenty years, EUS has become a cornerstone in the diagnostic phase of PNET management for its high diagnostic yield and the possibility of obtaining a histological specimen. The number of EUS applications in the PNET work-up has been rapidly increasing with new and powerful possibilities. The application of contrast has led to an important step in PNET detection; in recent years, it has been gaining interesting applications in aggressiveness assessment. In this review, we underline the latest experiences and opportunities in the behavior assessment of PNETs using contact-enhanced EUS and contested enhanced harmonic EUS with a particular focus on the future application and possibility that these techniques could provide.
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Affiliation(s)
- Gianluca Franchellucci
- Gastrointestinal Endoscopy Unit, Humanitas Mater Domini, 21053 Castellanza, Italy
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
| | - Marta Andreozzi
- Endoscopic Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
- Department of Clinical Medicine and Surgery, ‘Federico II’ University of Naples, 80131 Naples, Italy
| | - Silvia Carrara
- Endoscopic Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Luca De Luca
- Endoscopic Unit, ASST Santi Paolo e Carlo, 20142 Milan, Italy
| | - Francesco Auriemma
- Gastrointestinal Endoscopy Unit, Humanitas Mater Domini, 21053 Castellanza, Italy
| | - Danilo Paduano
- Gastrointestinal Endoscopy Unit, Humanitas Mater Domini, 21053 Castellanza, Italy
| | - Federica Calabrese
- Gastrointestinal Endoscopy Unit, Humanitas Mater Domini, 21053 Castellanza, Italy
| | - Antonio Facciorusso
- Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy
| | - Valeria Poletti
- Gastrointestinal Endoscopy Unit, Humanitas Mater Domini, 21053 Castellanza, Italy
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
| | - Alessandro Zerbi
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy
| | - Andrea Gerardo Lania
- Endocrinology, Diabetology and Medical Andrology Unit, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy
| | - Alexia Francesca Bertuzzi
- Medical Oncology and Hematology Unit, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy
| | - Paola Spaggiari
- Department of Pathology, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy
| | - Vittorio Pedicini
- Department of Interventional Radiology, Humanitas University, Humanitas Research Hospital IRCCS, 20089 Rozzano, Italy
| | - Marcello Rodari
- Department of Nuclear Medicine, IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Italy
| | - Pietro Fusaroli
- Gastroenterology Unit, Hospital of Imola, University of Bologna, 40126 Imola, Italy
| | - Andrea Lisotti
- Gastroenterology Unit, Hospital of Imola, University of Bologna, 40126 Imola, Italy
| | - Andrew Ofosu
- Division of Gastroenterology and Hepatology, University of Cincinnati, Cincinnati, OH 45221, USA
| | - Alessandro Repici
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Endoscopic Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Benedetto Mangiavillano
- Gastrointestinal Endoscopy Unit, Humanitas Mater Domini, 21053 Castellanza, Italy
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
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Impact of tumor size and location on endoscopic ultrasound-guided sampling of pancreatic neuroendocrine tumors: A recursive partitioning analysis. Pancreatology 2022; 22:644-650. [PMID: 35589512 DOI: 10.1016/j.pan.2022.04.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Revised: 04/20/2022] [Accepted: 04/26/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND Current guidelines provide weak recommendations to treat small (<2 cm) non-functional pancreatic neuroendocrine tumors with low Ki-67 proliferation index either by resection or clinical follow-up. However, there is a lack of consensus regarding the minimal size of pNET, which allows EUS-guided biopsy with high enough diagnostic accuracy for stratification. METHODS We conducted a retrospective, bicentric analysis of patients who had undergone EUS-guided pNET sampling in two tertiary care Endoscopy Units in Germany and Poland. Using a recursive partitioning of the tree-aided model, we aimed to stratify the probability of successful EUS-guided biopsy of pNET lesions according to their size and location. RESULTS In our pNET cohort, successful histological confirmation of a pNET diagnosis was achieved in 59/69 (85.5%) cases at the initial EUS-guided biopsy. In 41 patients with a pNET size less than 18.5 mm, the EUS-guided first biopsy was successful in 90.2%. In 16 of these patients with smaller lesions, EUS-guided sampling was 100% in very small (less than 11 mm) and extremely small lesions (less than 8 mm). The biopsy success rate was 100% in tail lesions in the size range between ≥5.95 and <8.1 mm but only 33.3% independent of the investigator in pancreatic head or body, with an error rate of 11.2% CONCLUSION: Using a recursive partitioning of the tree-aided stratification model, we demonstrate for the first time that in balancing risks and benefits, very small pNETs (<1 cm) in the tail of the pancreas should be sampled under EUS-guidance.
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Hickman K, Sadler T, Zhang T, Boninsegna E, Majcher V, Godfrey E. Pancreatic cystic lesions and the role of contrast enhanced endoscopic ultrasound. Clin Radiol 2022; 77:418-427. [PMID: 35387743 DOI: 10.1016/j.crad.2022.02.017] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 02/22/2022] [Indexed: 11/16/2022]
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Fang JM, Li J, Shi J. An update on the diagnosis of gastroenteropancreatic neuroendocrine neoplasms. World J Gastroenterol 2022; 28:1009-1023. [PMID: 35431496 PMCID: PMC8968521 DOI: 10.3748/wjg.v28.i10.1009] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 11/26/2021] [Accepted: 02/10/2022] [Indexed: 02/06/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) arise from neuroendocrine cells found throughout the gastrointestinal tract and islet cells of the pancreas. The incidence and prevalence of GEP-NENs have been increasing each year due to higher awareness, improved diagnostic modalities, and increased incidental detection on cross-sectional imaging and endoscopy for cancer screening and other conditions and symptoms. GEP-NENs are a heterogeneous group of tumors and have a wide range in clinical presentation, histopathologic features, and molecular biology. Clinical presentation most commonly depends on whether the GEP-NEN secretes an active hormone. The World Health Organization recently updated the classification of GEP-NENs to introduce a distinction between high-grade neuroendocrine tumors and neuroendocrine carcinomas, which can be identified using histology and molecular studies and are more aggressive with a worse prognosis compared to high-grade neuroendocrine tumors. As our understanding of the biology of GEP-NENs has grown, new and improved diagnostic modalities can be developed and optimized. Here, we discuss clinical features and updates in diagnosis, including histopathological analysis, biomarkers, molecular techniques, and radiology of GEP-NENs. We review established diagnostic tests and discuss promising novel diagnostic tests that are currently in development or require further investigation and validation prior to broad utilization in patient care.
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Affiliation(s)
- Jiayun M Fang
- Department of Pathology & Clinical Labs, University of Michigan, Ann Arbor, MI 48109, United States
| | - Jay Li
- Medical Scientist Training Program, University of Michigan, Ann Arbor, MI 48109, United States
| | - Jiaqi Shi
- Department of Pathology & Clinical Labs, University of Michigan, Ann Arbor, MI 48109, United States
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Chagpar R, Naples R, Siperstein AE. Pancreatic Neuroendocrine Tumors. PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2021:938-948.e4. [DOI: 10.1016/b978-0-323-67293-1.00084-0] [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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Kalantri S, Bakshi P, Verma K. Grading of pancreatic neuroendocrine tumors on endoscopic ultrasound-guided fine-needle aspiration using Ki-67 index and 2017 World Health Organization criteria: An analysis of 32 cases. Cytojournal 2020; 17:21. [PMID: 33093857 PMCID: PMC7568229 DOI: 10.25259/cytojournal_4_2020] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Accepted: 05/12/2020] [Indexed: 01/15/2023] Open
Abstract
Objectives: Biological behavior of pancreatic neuroendocrine tumors (Pan NETs) is difficult to predict on morphology alone. The assessment of proliferation by the Ki-67 proliferation index (PI) is considered to be an important prognostic parameter in these tumors and has been endorsed by the 2017 World Health Organization (WHO) grading system for Pan NETs. Although widely accepted on surgical specimens, there is varied opinion on grading of these tumors on cytology samples. This study aimed at classification and grading of Pan NETs on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) using the recent 2017 WHO criteria and assess the reliability of Ki-67 grading by comparing it with histology samples wherever available. Material and Methods: Search of cytopathology lab records over a 3-year period (June 2015–May 2018) revealed 33 cases of pancreatic NETs diagnosed on EUS-FNA specimens. Using the guidelines of 2017 WHO classification and grading of Pan NETs, retrospective grading of these Pan NETs was done. They were graded as Grades 1, 2, and 3 well differentiated Pan NETs and poorly differentiated Grade 3 neoplasms based on Ki-67 PI and cytomorphology. Cytomorphological features were compared across the three grades. The cytological grading was then compared with the histological grading where available. Results: Ki-67 grading on cytology was done in 32 cases (22 on cell block and 10 on smears), of which 19 (59.4%) were Grade 1, 8 (25%) were Grade 2, and 5 (15.6%) were Grade 3 tumors. The most common cytomorphological features observed in Grade 1 tumors were small round uniform cells with granular chromatin and prominent plasmacytoid morphology. As the grade increased, tumor cells showed increased pleomorphism, angulated nuclei, and less frequent plasmacytoid cells. Histopathology (biopsy/resected specimens) was available in 11 of the 32 cases. Comparison of grading on cytology and histology showed concordance in ten of the 11 cases (k value = 0.862). Conclusion: Our data suggest that grading of Pan NETs by assessing Ki-67 PI on cytology samples collected by EUS-FNA shows good agreement with that measured on histology samples.
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Affiliation(s)
- Sweety Kalantri
- Department of Cytopathology, Sir Ganga Ram Hospital, Central Delhi, New Delhi, India,
| | - Pooja Bakshi
- Department of Cytopathology, Sir Ganga Ram Hospital, Central Delhi, New Delhi, India,
| | - Kusum Verma
- Department of Cytopathology, Sir Ganga Ram Hospital, Central Delhi, New Delhi, India,
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Li X, Zhu H, Qian X, Chen N, Lin X. MRI Texture Analysis for Differentiating Nonfunctional Pancreatic Neuroendocrine Neoplasms From Solid Pseudopapillary Neoplasms of the Pancreas. Acad Radiol 2020; 27:815-823. [PMID: 31444110 DOI: 10.1016/j.acra.2019.07.012] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Revised: 07/16/2019] [Accepted: 07/23/2019] [Indexed: 12/12/2022]
Abstract
RATIONALE AND OBJECTIVES To evaluate the value of texture analysis on preoperative magnetic resonance imaging (MRI) for identifying nonfunctional pancreatic neuroendocrine neoplasms (NF-PNENs) and solid pseudopapillary neoplasms (SPNs). MATERIALS AND METHODS This retrospective study included 119 patients who underwent MRI, including T2-weighted imaging with fat-suppression, diffusion-weighted imaging (DWI), apparent diffusion coefficient, precontrast T1-weighted imaging with fat-suppression (T1WI+fs), and dynamic contrast-enhanced (DCE)-T1WI+fs. Raw data analysis, principal component analysis, linear discriminant analysis, and nonlinear discriminant analysis (NDA) were used to classify NF-PNENs and SPNs. The results are reported as misclassification rates. The images were simultaneously evaluated by an experienced senior radiologist without knowledge of the pathological results. The misclassification rate of the radiologist was compared to the MaZda (texture analysis software) results. Neural network classifier testing was used for validation. In addition, 30 textures for each MRI sequence were investigated. RESULTS The misclassification rate of NDA was lower than that of other analyses. In NDA, DWI obtained the lowest value of 7.92%, but there was no significant difference among the sequences. The misclassification rate of the radiologist (34.65%) was significantly higher than that of NDA for all sequences. The validation results were good in the arterial phase and delayed phase. In the training set, entropy and sum entropy were optimal texture features on DWI and precontrast T1WI+fs, while the mean and percentile seemed to be the more discriminative features on DCE-T1WI+fs. CONCLUSION Texture analysis can sensitively distinguish between NF-PNENs and SPNs on MRI, and percentile and mean of DCE-T1WI+fs images were informative for differentiation of neoplasms.
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Affiliation(s)
- Xudong Li
- Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai 200025, China
| | - Hui Zhu
- Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Xiaohua Qian
- Institute for Medical Imaging Technology, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Nan Chen
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaozhu Lin
- Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai 200025, China.
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Eusebi LH, Thorburn D, Toumpanakis C, Frazzoni L, Johnson G, Vessal S, Luong TV, Caplin M, Pereira SP. Endoscopic ultrasound-guided fine-needle aspiration vs fine-needle biopsy for the diagnosis of pancreatic neuroendocrine tumors. Endosc Int Open 2019; 7:E1393-E1399. [PMID: 31673610 PMCID: PMC6805236 DOI: 10.1055/a-0967-4684] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Accepted: 06/03/2019] [Indexed: 02/07/2023] Open
Abstract
Background and study aims Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) as a method of obtaining preoperative diagnosis of pancreatic neuroendocrine tumors (PanNETs) has been reported in several series. Fine-needle biopsies (FNB) are increasingly employed to obtain core specimens during EUS. However, the differences in efficacy between these sampling methods in the diagnosis of PanNETs still needs to be defined. Patients and methods Over a 13-year period, all patients who underwent EUS-guided tissue sampling of suspicious pancreatic lesions with clinical, endoscopic and pathologic details were entered into an electronic database. Lesions underwent EUS-FNA or FNB sampling, or a combination of the two. The accuracy and safety of different EUS-guided sampling methods for confirmed PanNETs were investigated. Results A total of 91 patients (M/F: 42/49, median age: 57 years), who underwent 102 EUS procedures had a final diagnosis of PanNET. Both EUS-guided sampling modalities were used in 28 procedures, EUS-FNA alone was used in 61 cases, while EUS-FNB alone in 13 cases. Diagnostic yield of EUS-FNA and EUS-FNB alone, including the inadequate specimens, was 77.5 % (95 %CI: 68.9 - 86.2 %) and 85.4 % (95 %CI: 74.6 - 96.2 %), respectively. The combination of both sampling modalities established the diagnosis in 96.4 % of cases (27/28) (95 %CI: 89.6 - 100 %), significantly superior to EUS-FNA alone ( P = 0.023). Diagnostic sensitivity among the adequate samples for EUS-FNA, EUS-FNB and for the combination of the two methods was 88.4 % (95 %CI: 80.9 - 96.0 %), 94.3 % (95 %CI: 86.6 - 100 %) and 100 % (95 %CI: 100 - 100 %). There was one reported complication, a post-FNA bleeding, treated conservatively. Conclusions EUS-FNB improves diagnostic sensitivity and confers additional information to cytological assessment of PanNETs.
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Affiliation(s)
- Leonardo H. Eusebi
- HPB endoscopy unit, Royal Free Hospital NHS Trust, London, UK,Department of Medical and Surgical Sciences, University of Bologna, Italy
| | | | - Christos Toumpanakis
- Neuroendocrine Tumour Unit, Centre for Gastroenterology, Royal Free Hospital NHS Trust, London, UK
| | - Leonardo Frazzoni
- Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Gavin Johnson
- HPB endoscopy unit, Royal Free Hospital NHS Trust, London, UK,Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | - Sheida Vessal
- HPB endoscopy unit, Royal Free Hospital NHS Trust, London, UK
| | - Tu Vinh Luong
- Department of Cellular Pathology, Royal Free London NHS Foundation, London, UK
| | - Martyn Caplin
- Neuroendocrine Tumour Unit, Centre for Gastroenterology, Royal Free Hospital NHS Trust, London, UK
| | - Stephen P. Pereira
- Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK,Institute for Liver & Digestive Health, University College London, UK,Corresponding author Prof. Stephen P. Pereira The UCL Institute for Liver & Digestive HealthNW3 2PFUK+4407729632540
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Abstract
Vasoactive intestinal peptide-secreting tumors (VIPomas) are a group of rare neuroendocrine tumors, which cause a typical syndrome of watery diarrhea. Most of these tumors are found in the pancreas and are usually detected at a later stage. Although curative resection is not possible in most of these tumors, both symptom and tumor control can be achieved by a multidimensional approach, to enable a long survival of most patients. There are no clear-cut guidelines for the management of VIPomas because of the rarity of this neoplasm and lack of prospective data. In this review, we discuss the available evidence on the clinical features and management of these rare tumors.
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12
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Gao L, Natov NS, Daly KP, Masud F, Chaudhry S, Sterling MJ, Saif MW. An update on the management of pancreatic neuroendocrine tumors. Anticancer Drugs 2019; 29:597-612. [PMID: 29782352 DOI: 10.1097/cad.0000000000000633] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Pancreatic neuroendocrine tumors (PNETs) are a rare and heterogeneous group of neoplasia and differ in their clinical presentation, behavior, and prognosis based on both histological features and cancer stage at the time of diagnosis. Although small-sized tumors can be surgically resected, locally advanced and metastatic tumors confer a poor prognosis. In addition, only limited treatment options are available to the latter group of patients with PNETs, such as hormonal analogs, cytotoxic agents, and targeted therapy. In selected patients, liver-directed therapies are also used. As expected, clinicians taking care of these patients are challenged to develop an effective and comprehensive treatment strategy for their patients amid a wide variety of treatment modalities. Targeted therapy for PNETs is limited to sunitinib and everolimus. Presently, a number of clinical studies are ongoing to assess the efficacy of newer targeted agents alone and in combination with previous agents for the treatment of advanced PNETs. The authors reviewed the current treatment and also discussed the emerging agents and emphasized the need to identify biomarkers.
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Affiliation(s)
- Limin Gao
- Division of Hematology and Oncology, GI Oncology Program and Experimental Therapeutics
| | - Nikola S Natov
- Division of Gastroenterology, Tufts University School of Medicine, Boston, Massachusetts, USA
| | | | | | - Sadia Chaudhry
- Foundation University Medical College, Rawalpindi, Pakistan
| | - Mark J Sterling
- Division of Gastroenterology, Tufts University School of Medicine, Boston, Massachusetts, USA
| | - Muhammad W Saif
- Division of Hematology and Oncology, GI Oncology Program and Experimental Therapeutics
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Dhaliwal AJS, Strosberg JR, Centeno BA, Vignesh S. Diagnostic performance of endoscopic ultrasound-guided fine-needle aspiration for cystic and non-cystic pancreatic neuroendocrine tumors. Endosc Int Open 2019; 7:E854-E859. [PMID: 31286055 PMCID: PMC6611730 DOI: 10.1055/a-0915-9496] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Accepted: 02/22/2019] [Indexed: 12/13/2022] Open
Abstract
Background and study aims Pancreatic neuroendocrine tumors (P-NENs) are rare tumors with malignant potential. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been shown to be superior to other imaging methods in preoperative localization and diagnosis of P-NENs. The objective of this study was to describe the EUS features of non-metastatic cystic and non-cystic P-NENs seen at a referral center and to evaluate the performance of EUS-FNA in diagnosis of P-NENs. Patients and methods All patients with histologically confirmed, non-metastatic P-NENs, which underwent EUS-FNA prior to surgical resection at the Moffitt Cancer Center between Jan 2005 and Dec 2012 were included. Clinical, endoscopic and pathologic information was abstracted from electronic medical records. Results Thirty-nine patients, all with non-functional P-NENs, were included in this study. Thirteen tumors were cystic and 26 were solid. Among the cystic tumors, 50 % were partly cystic and partly solid, and 50 % were fully cystic. The cystic tumors were more commonly seen at the body/tail, and the solid tumors were more uniformly distributed. Fluid could be aspirated from 50 % of the cystic tumors, all with a carcinoembryonic antigen level < 192 ng/mL. With surgical pathology as the gold standard, overall sensitivity of EUS-FNA in diagnosing cystic tumors was 62.5 %, and for solid tumors, 95 % ( P < 0.03). Conclusions EUS-FNA is much more sensitive in diagnosing solid P-NENs than cystic PNETs. Our results indicate that EUS-FNA may have higher sensitivity for diagnosis of cystic P-NENs than the reported sensitivity of EUS-FNA for all pancreatic cystic tumors.
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Affiliation(s)
- Amaninder Jeet Singh Dhaliwal
- Department of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, Nebraska, United States
| | - Jonathan R. Strosberg
- H. Lee Moffitt Cancer Center and Research Institute and University of South Florida College of Medicine, Tampa, Florida, United States
| | - Barbara A. Centeno
- H. Lee Moffitt Cancer Center and Research Institute and University of South Florida College of Medicine, Tampa, Florida, United States
| | - Shivakumar Vignesh
- Division of Gastroenterology and Hepatology, SUNY Health Sciences Center at Brooklyn, Brooklyn, New York, United States
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14
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Yohanathan L, Dossa F, St Germain AT, Golbafian F, Moulton CA, McGilvray ID, Greig PD, Serra S, Wei AC, Jhaveri KS, Gallinger S, Cleary SP. Management and surveillance of non-functional pancreatic neuroendocrine tumours: Retrospective review. Pancreatology 2019; 19:360-366. [PMID: 30803874 DOI: 10.1016/j.pan.2019.02.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Revised: 02/11/2019] [Accepted: 02/12/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND /Objective. To determine the outcomes of a non-operative management approach for sporadic, small, non-functional pancreatic neuroendocrine tumours. METHODS A retrospective chart review of patients with non-functional pancreatic neuroendocrine tumours initially managed non-operatively at a single institution was performed. Patients were identified through a search of radiologic reports, and individuals with ≥2 cross-sectional imaging studies performed >6 months apart from Jan. 1, 2000 to Dec. 31, 2013 were included. Data on tumour size, radiologic characteristics at diagnosis, interval radiologic growth, and surgical outcomes were recorded. RESULTS Over the thirteen-year study period, 95 patients met inclusion criteria and were followed radiologically for a median of 36 months (18-69 months). Median initial tumour size on first imaging was 14.0 mm (IQR 10-19 mm). Median overall tumour growth rate was 0.03 mm/month (IQR: 0.00-0.14 mm/month). There was no significant relationship between initial tumour size and growth rate for tumours ≤ 2 cm or for lesions between 2 and 4 cm. Thirteen (14%) patients initially managed non-operatively underwent resection during the follow-up period. Reasons for surgery included interval tumour growth, patient anxiety or preference, or diagnostic uncertainty. Median time to surgery was 14 months (IQR 8-19 months). No patients progressed beyond resectability or developed metastatic disease during the observation period. CONCLUSION For patients with sporadic, small, non-functional pancreatic neuroendocrine tumours, radiologic surveillance appears to be a safe initial approach to management.
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Affiliation(s)
- Lavanya Yohanathan
- Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Fahima Dossa
- Division of General Surgery, University of Toronto, Toronto, ON, Canada
| | | | | | - Carol-Anne Moulton
- Division of General Surgery, University of Toronto, Toronto, ON, Canada; Department of Surgery, University Health Network, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
| | - Ian D McGilvray
- Division of General Surgery, University of Toronto, Toronto, ON, Canada; Department of Surgery, University Health Network, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
| | - Paul D Greig
- Division of General Surgery, University of Toronto, Toronto, ON, Canada; Department of Surgery, University Health Network, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
| | - Stefano Serra
- Department of Pathology, University Health Network/University of Toronto, Canada
| | - Alice C Wei
- Department of Surgery, University Health Network, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
| | - Kartik S Jhaveri
- Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital and Women's College Hospital, University of Toronto, Toronto, ON, Canada
| | - Steve Gallinger
- Division of General Surgery, University of Toronto, Toronto, ON, Canada; Department of Surgery, University Health Network, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
| | - Sean P Cleary
- Division of General Surgery, University of Toronto, Toronto, ON, Canada; Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN, USA; Department of Surgery, University Health Network, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
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15
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Simple Vascular Architecture Classification in Predicting Pancreatic Neuroendocrine Tumor Grade and Prognosis. Dig Dis Sci 2018; 63:3147-3152. [PMID: 30121810 DOI: 10.1007/s10620-018-5240-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Accepted: 08/01/2018] [Indexed: 12/26/2022]
Abstract
BACKGROUND AND AIM Vascularity is a critical feature in the evaluation of pancreatic neuroendocrine tumor (PNET). When done by EUS, contrast agents are recommended. However, vascular architecture (VA) can also be evaluated by routine Doppler flow in EUS without contrast agents. Our aim was to provide a simple VA classification in EUS for PNET grade and prognosis. METHODS All pathologically proven PNET cases with EUS between 2012 and 2018 were retrospectively analyzed. The Doppler imaging was retrieved for VA classification. Predictive model construction was performed by machine learning algorithms. RESULTS A total of 112 PNET cases were evaluated, among which 93 cases were subjected to VA classification. The VA was classified into type A (peritumoral with or without intratumoral vessels [A1 or A2]); type B (only intratumoral vessels); and type C (flow was absent). The VA classification was significantly correlated with tumor grades: 74% type A1 was G1, 73% type B was G2, and 58% type C was G3. Multivariate analysis indicated that elevated serum CA19-9 and type C classification were the independent predictors of G3 tumor. Five machine learning models were constructed, among which random forest was the best one with an AUC of 0.9972. Low-risk patients classified by this model exhibited better prognosis than high-risk patients (p = 0.0087). CONCLUSIONS In the novel simple VA classification, peritumoral, intratumoral, and absent vessels are prone to be G1, G2, and G3, respectively. Combined with serum CA19-9 and lesion size, the VA classification could predict tumor grade and prognosis in PNET.
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16
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Escartín R, Brun N, García Monforte MN, Ferreres JC, Corripio R. Insulinoma: A Rare Cause of Hypoglycemia in Childhood. AMERICAN JOURNAL OF CASE REPORTS 2018; 19:1121-1125. [PMID: 30237390 PMCID: PMC6161565 DOI: 10.12659/ajcr.910426] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Patient: Male, 11 Final Diagnosis: Insulinoma Symptoms: Dizziness • psychological issues Medication: — Clinical Procedure: — Specialty: Endocrinology and Metabolic
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Affiliation(s)
- Rocío Escartín
- Department of Pediatric Endocrinology, Parc Taulí Hospital Universitari, Research and Innovation Institute Parc Taulí I3PT, Autonomous University of Barcelona, Sabadell, Spain
| | - Nuria Brun
- Department of Surgery, Parc Taulí Hospital Universitari, Research and Innovation Institute Parc Taulí I3PT, Autonomous University of Barcelona, Sabadell, Spain
| | - M Nieves García Monforte
- Department of Surgery, Parc Taulí Hospital Universitari, Research and Innovation Institute Parc Taulí I3PT, Autonomous University of Barcelona, Sabadell, Spain
| | - Joan Carles Ferreres
- Department of Pathology, Parc Taulí Hospital Universitari, Research and Innovation Institute Parc Taulí I3PT, Autonomous University of Barcelona, Sabadell, Spain
| | - Raquel Corripio
- Department of Pediatric Endocrinology, Parc Taulí Hospital Universitari, Research and Innovation Institute Parc Taulí I3PT, Autonomous University of Barcelona, Sabadell, Spain
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17
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Okumura Y, Noda T, Eguchi H, Iwagami Y, Yamada D, Asaoka T, Kawamoto K, Gotoh K, Kobayashi S, Umeshita K, Hashimoto Y, Takeda Y, Tanemura M, Shigekawa M, Morii E, Takehara T, Mori M, Doki Y. Middle segment pancreatectomy for a solid serous cystadenoma diagnosed by MRCP and review of the literature: A case report. Mol Clin Oncol 2018; 8:675-682. [PMID: 29725534 PMCID: PMC5920357 DOI: 10.3892/mco.2018.1598] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Accepted: 03/20/2018] [Indexed: 01/02/2023] Open
Abstract
Solid serous cystadenoma of the pancreas is the rarest subtype of serous cystadenoma. Cystic structures are difficult to recognize by imaging studies. In the clinical setting, it is crucial to discriminate a solid serious cystadenoma from other solid pancreatic tumors. The present study reported a case of solid serous cystadenoma in which the magnetic resonance cholangiopancreatography (MRCP) findings were useful for diagnosis and decision-making regarding the surgical strategy, with a review of the previous reports of solid serous cystadenoma. A 50-year-old woman was referred to our hospital for investigation of a pancreatic body mass. A 2-cm hypervascular solid tumor was revealed by computed tomography. No typical radiological imaging findings of small cysts were detected, such as a honeycomb structure, and an adequate specimen could not be gained by biopsy under endoscopic ultrasonography. However, the tumor showed high intensity on MRCP, suggesting its cystic nature. A solid serous cystadenoma was suspected based on these radiological findings, and middle segment pancreatectomy was performed as a function-preserving surgery. The histological findings were compatible with a solid serous cystadenoma. In conclusion, MRCP imaging may be helpful for diagnosis and decision-making regarding the most appropriate surgical method for solid serous cystadenomas.
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Affiliation(s)
- Yuichiro Okumura
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - Takehiro Noda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - Yoshifumi Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - Daisaku Yamada
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - Tadafumi Asaoka
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - Koichi Kawamoto
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - Kunihito Gotoh
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - Koji Umeshita
- Division of Health Science, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - Yasuji Hashimoto
- Department of Surgery, Yao Municipal Hospital, Osaka 581-0069, Japan
| | - Yutaka Takeda
- Department of Surgery, Kansai Rosai Hospital, Hyogo 660-8511, Japan
| | | | - Minoru Shigekawa
- Departments of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - Eiichi Morii
- Department of Pathology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - Tetsuo Takehara
- Departments of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - Masaki Mori
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
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18
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Zilli A, Arcidiacono PG, Conte D, Massironi S. Clinical impact of endoscopic ultrasonography on the management of neuroendocrine tumors: lights and shadows. Dig Liver Dis 2018; 50:6-14. [PMID: 29102525 DOI: 10.1016/j.dld.2017.10.007] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Revised: 10/04/2017] [Accepted: 10/09/2017] [Indexed: 02/07/2023]
Abstract
The incidence of gastroenteropancreatic neuroendocrine neoplasms has increased in the recent decades. An extensive bibliographical search was performed in PubMed to identify guidelines and primary literature (retrospective and prospective studies, systematic reviews, case series) published mostly between year 1997 and June 2017, using both medical subject heading (MeSH) terms and free-language keywords about the accuracy and diagnostic and therapeutic role of endoscopic ultrasound in the context of gastro-entero-pancreatic neuroendocrine neoplasms. Endoscopic ultrasound is the modality of choice for diagnosing pancreatic neuroendocrine neoplasms and for the locoregional staging of gastric, duodenal, pancreatic and rectal neuroendocrine neoplasms; in particular, in the setting of pancreatic neuroendocrine neoplasms it has demonstrated higher accuracy in tumor detection than other imaging modalities. Furthermore, the possibility of tattooing pancreatic lesions by endoscopic ultrasound fine needle aspiration may help surgeons to locate the tumor and avoid any demolition surgery. Finally, endoscopic ultrasound-guided therapies have been proposed and used in several studies for patients unsuitable for surgery, with good results on the control of symptoms and the reduction of tumor burden.
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Affiliation(s)
- Alessandra Zilli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy; Postgraduate School of Gastroenterology, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Paolo Giorgio Arcidiacono
- PancreatoBiliary Endoscopy and Endosonography Division, Pancreas Translatiinal and Clinical Research Center, San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy
| | - Dario Conte
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy
| | - Sara Massironi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy.
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19
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Chai SM, Brown IS, Kumarasinghe MP. Gastroenteropancreatic neuroendocrine neoplasms: selected pathology review and molecular updates. Histopathology 2017; 72:153-167. [DOI: 10.1111/his.13367] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Siaw M Chai
- PathWest Laboratory Medicine; Queen Elizabeth II Medical Centre; Perth Australia
| | - Ian S Brown
- Envoi Pathology; Kelvin Grove; Queensland Australia
| | - M Priyanthi Kumarasinghe
- PathWest Laboratory Medicine; Queen Elizabeth II Medical Centre; Perth Australia
- School of Pathology and Laboratory Medicine; University of Western Australia; Perth Australia
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20
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Management of Well-differentiated Gastroenteropancreatic Neuroendocrine Tumors (GEPNETs): A Review. Clin Ther 2017; 39:2146-2157. [PMID: 29173655 DOI: 10.1016/j.clinthera.2017.10.010] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Revised: 10/05/2017] [Accepted: 10/05/2017] [Indexed: 12/31/2022]
Abstract
PURPOSE Neuroendocrine tumors (NETs) are heterogeneous tumors that arise from the neuroendocrine cells of the digestive tract and other organs, such as the lung, ovary, and thyroid glands. They can be well differentiated or poorly differentiated, and management of these tumors differs for each histologic subtype. We have performed a review of NETs and focused on management of well-differentiated gastroenteropancreatic neuroendocrine tumors (GEPNETs) and carcinoid syndrome. METHODS A PubMed search was performed to obtain articles on the management of well-differentiated NETs. Using the key words neuroendocrine tumors, carcinoid, pNET, octreotide, somatostatin analogues, and radiolabeled therapy, we reviewed Phase II and III trials that were published over the past 30 years. We also reviewed guidelines from the European Neuroendocrine Tumor Society, North America Neuroendocrine Tumor Society, and National Comprehensive Cancer Network in our search. FINDINGS NETs are usually slow-growing tumors that remain asymptomatic for a long duration and can be either nonfunctioning or functioning. Surgical resection is recommended for locoregional disease, impending obstruction, symptom control, and advanced disease. Nonsurgical treatment options include somatostatin analogues (SSAs), multikinase inhibitors, targeted therapy, chemotherapy, and radiolabeled SSAs. Carcinoid syndrome is mainly treated with SSAs. IMPLICATIONS Although GEPNETs are slow-growing tumors, most patients are diagnosed with metastatic disease, and therefore it is important that the management of each patient be discussed in a multidisciplinary setting to optimize the treatment strategy. Patients should be considered for clinical trials and refractory cases referred to a specialty center.
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21
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Abstract
Imaging of the endocrine pancreas is dominated by neuroendocrine tumors, a diverse category of neoplasms that may or may not cause symptoms from hormone hypersecretion. These tumors may also be evidence of several different genetic syndromes. Understanding the usefulness of different imaging modalities and entities that simulate neuroendocrine tumors is key for both radiologists and referring physicians.
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Affiliation(s)
- Mark Masciocchi
- Department of Radiology, UMass Memorial Medical Center, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
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22
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Carr RA, Yip-Schneider MT, Dolejs S, Hancock BA, Wu H, Radovich M, Schmidt CM. Pancreatic Cyst Fluid Vascular Endothelial Growth Factor A and Carcinoembryonic Antigen: A Highly Accurate Test for the Diagnosis of Serous Cystic Neoplasm. J Am Coll Surg 2017; 225:93-100. [PMID: 28633941 PMCID: PMC6037560 DOI: 10.1016/j.jamcollsurg.2017.05.003] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Revised: 04/03/2017] [Accepted: 05/05/2017] [Indexed: 12/18/2022]
Abstract
Accurate differentiation of pancreatic cystic lesions is important for early detection and prevention of pancreatic cancer, as well as avoidance of unnecessary surgical intervention. Serous cystic neoplasms (SCNs) have no malignant potential, but can mimic the following premalignant mucinous cystic lesions: mucinous cystic neoplasm and intraductal papillary mucinous neoplasm (IPMN). We recently identified vascular endothelial growth factor (VEGF)-A as a novel pancreatic fluid biomarker for SCN. We hypothesize that combining cyst fluid CEA with VEGF-A will improve the diagnostic accuracy of VEGF-A. Pancreatic cyst/duct fluid was collected from consenting patients undergoing surgical cyst resection with corresponding pathologic diagnoses. Pancreatic fluid VEGF-A and CEA levels were detected by ELISA. One hundred and forty-nine patients with pancreatic cystic lesions met inclusion criteria. Pathologic diagnoses included pseudocyst (n = 14), SCN (n = 26), mucinous cystic neoplasm (n = 40), low-/moderate-grade IPMN (n = 34), high-grade IPMN (n = 20), invasive IPMN (n = 10), and solid pseudopapillary neoplasm (n = 5). Vascular endothelial growth factor A was significantly elevated in SCN cyst fluid compared with all other diagnoses (p < 0.001). With a threshold of >5,000 pg/mL, VEGF-A alone has 100% sensitivity and 83.7% specificity to distinguish SCNs from other cystic lesions. With a threshold of ≤10 ng/mL, CEA alone identifies SCN with 95.5% sensitivity and 81.5% specificity. Sensitivity and specificity of the VEGF-A/CEA combination are 95.5% and 100%, respectively. The c-statistic increased from 0.98 to 0.99 in the receiver operating characteristic analysis when CEA was added to VEGF-A alone. Although VEGF-A alone is a highly accurate test for SCN, the combination of VEGF-A with CEA approaches the gold standard for pathologic diagnosis, importantly avoiding false positives. Patients with a positive test indicating benign SCN can be spared a high-risk surgical pancreatic resection.
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Affiliation(s)
- Rosalie A. Carr
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
- Department of Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN
| | - Michele T. Yip-Schneider
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
- Department of Walther Oncology Center, Indianapolis, IN
- Department of Indiana University Cancer Center, Indianapolis, IN
- Department of Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN
| | - Scott Dolejs
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
| | - Bradley A. Hancock
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
| | - Huangbing Wu
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
- Department of Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN
| | - Milan Radovich
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
- Department of Walther Oncology Center, Indianapolis, IN
- Department of Indiana University Cancer Center, Indianapolis, IN
| | - C. Max Schmidt
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
- Department of Biochemistry/Molecular Biology, Indiana University School of Medicine, Indianapolis, IN
- Department of Walther Oncology Center, Indianapolis, IN
- Department of Indiana University Cancer Center, Indianapolis, IN
- Department of Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN
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23
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Richmond AM, Mehrotra S. Two unusual variants of pancreatic neuroendocrine tumor and their potential pitfalls on fine-needle aspiration cytology. Diagn Cytopathol 2017; 45:371-378. [PMID: 28217985 DOI: 10.1002/dc.23662] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2016] [Revised: 11/07/2016] [Accepted: 12/13/2016] [Indexed: 12/19/2022]
Abstract
Endoscopic ultrasound-guided fine-needle aspiration is increasingly utilized for the diagnosis of pancreatic lesions. Although operator dependent, the procedure has good overall performance characteristics and is minimally invasive; however, accuracy and sensitivity are reportedly lower for pancreatic neuroendocrine tumor (PanNET) compared with the more common pancreatic ductal adenocarcinoma (pACA). The underperformance is further exacerbated by the unusual cases of PanNET presenting with variant cytomorphology. We report two separate diagnostically challenging cases: a pigmented PanNET and a clear cell PanNET. We briefly review the literature and emphasize the importance of recognizing these uncommon variants when encountered in aspirate material. Diagn. Cytopathol. 2017;45:371-378. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Abby M Richmond
- Department of Pathology, University of Colorado, Aurora, Colorado
| | - Sanjana Mehrotra
- Department of Pathology, University of Colorado, Aurora, Colorado
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24
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Can MDCT or EUS features predict the histopathological grading scheme of pancreatic neuroendocrine neoplasms? Radiol Med 2017; 122:319-326. [PMID: 28176217 DOI: 10.1007/s11547-017-0727-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2016] [Accepted: 01/22/2017] [Indexed: 01/29/2023]
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25
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Yang G, Ji M, Chen J, Chen R, Chen Y, Fu D, Hou B, Huang H, Jiang L, Jin K, Ke N, Li Y, Li Y, Liang H, Liu A, Luo J, Ni Q, Shao C, Shen B, Sheng W, Song B, Sun J, Tan C, Tan H, Tang Q, Tang Y, Tian X, Wang J, Wang J, Wang W, Wang W, Wu Z, Xu J, Yan Q, Yang N, Yang Y, Yin X, Yu X, Yuan C, Zeng S, Zhang G, Zhang R, Zhou Z, Zhu Z, Shao C. Surgery management for sporadic small (≤2 cm), non-functioning pancreatic neuroendocrine tumors: a consensus statement by the Chinese Study Group for Neuroendocrine Tumors (CSNET). Int J Oncol 2017; 50:567-574. [PMID: 28035372 DOI: 10.3892/ijo.2016.3826] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2016] [Accepted: 12/12/2016] [Indexed: 11/05/2022] Open
Abstract
The incidence of small (≤2 cm), non-functioning pancreatic neuroendocrine tumors (NF-pNETs) increased in the last decades. Before making appropriate strategy for patients with NF-pNETs ≤2 cm, pathological confirmation is vital. Incidentally diagnosed, sporadic small NF-pNETs may bring aggressive behavior and poor prognosis, such as extrapancreatic extension, lymph nodal metastasis, distant metastasis and recurrence, even causing disease-related death. Understanding and formulating an appropriate strategy for the patients with sporadic small, non-functioning pancreatic neuroendocrine tumors have been controversial for some time. Although several studies have reported that patients with NF-pNETs ≤2 cm had less rate of malignant behavior compared with larger ones (>2 cm); and the surgery approach may leading to surgery-related pancreatic complications; but there is still a lack of level I evidence to convince surgeons to abandon all cases with sporadic small NF-pNETs. Based on an updated literature search and review, the members of the Chinese Study Group for Neuroendocrine Tumors (CSNET) from high-volume centers have reached a consensus on the issue of the management strategy for the sporadic small NF-pNETs. We recommend that, except for some selected patients with NF-pNETs <1 cm, incidentally discovered and unacceptable surgical risks, all others with NF-pNETs ≤2 cm should undergo tumor resection with lymph node dissection or at least lymph node sampling and careful postoperative surveillance.
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Affiliation(s)
- Guang Yang
- Department of General Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, P.R. China
| | - Meng Ji
- Department of General Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, P.R. China
| | - Jie Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Rufu Chen
- Department of Hepatopancreatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Ye Chen
- Department of Gastroenterology, Nanfang Hospial, Southern Medical University, Guangzhou, Guangdong, P.R. China
| | - Deliang Fu
- Department of Pancreatic Surgery, Pancreatic Disease Institute, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, P.R. China
| | - Baohua Hou
- Department of General Surgery, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, P.R. China
| | - Heguang Huang
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, P.R. China
| | - Liming Jiang
- Department of Radiology, Cancer Hospital/Institute, Chinese Academy of Medical Sciences, Beijing, P.R. China
| | - Kaizhou Jin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University; Pancreatic Cancer Institute, Fudan University, Shanghai, P.R. China
| | - Nengwen Ke
- Department of Hepatobiliary and Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China
| | - Ying Li
- Department of Radiology, Peking University Cancer Hospital and Institute, Beijing, P.R. China
| | - Yong Li
- Department of General Surgery, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, P.R. China
| | - Houjie Liang
- Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing, P.R. China
| | - An'an Liu
- Department of General Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, P.R. China
| | - Jie Luo
- Department of Pathology, China-Japan Friendship Hospital, Beijing, P.R. China
| | - Quanxing Ni
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University; Pancreatic Cancer Institute, Fudan University, Shanghai, P.R. China
| | - Chengwei Shao
- Department of Radiology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, P.R. China
| | - Boyong Shen
- Department of General Surgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
| | - Weiqi Sheng
- Department of Pathology, Shanghai Cancer Center, Fudan University, Shanghai, P.R. China
| | - Bin Song
- Department of Pancreatic Surgery, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, P.R. China
| | - Jian Sun
- Department of Hepatopancreatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Chunlu Tan
- Department of Hepatobiliary and Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China
| | - Huangying Tan
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing, P.R. China
| | - Qiyun Tang
- Department of Gastroenterology, Jiangsu People's Hospital, Nanjing Medical University, Nanjing, Jiangsu, P.R. China
| | - Yingmei Tang
- Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, Yunnan Research Center for Liver Diseases, Kunming, Yunnan, P.R. China
| | - Xiaodong Tian
- Department of General Surgery, Peking University First Hospital, Beijing, P.R. China
| | - Jian Wang
- Department of Biliary and Pancreatic Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
| | - Jie Wang
- Department of General Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Wei Wang
- Department of General Surgery, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai, P.R. China
| | - Wei Wang
- Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P.R. China
| | - Zheng Wu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China
| | - Jin Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University; Pancreatic Cancer Institute, Fudan University, Shanghai, P.R. China
| | - Qiang Yan
- Department of Surgery, Huzhou Central Hospital, Huzhou, Zhejiang, P.R. China
| | - Ning Yang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, P.R. China
| | - Yinmo Yang
- Department of General Surgery, Peking University First Hospital, Beijing, P.R. China
| | - Xiaoyu Yin
- Department of Biliary and Pancreatic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University; Pancreatic Cancer Institute, Fudan University, Shanghai, P.R. China
| | - Chunhui Yuan
- Department of General Surgery, Peking University Third Hospital, Peking University, Beijing, P.R. China
| | - Shan Zeng
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China
| | - Guochao Zhang
- Department of General Surgery, China-Japan Friendship Hospital, Beijing, P.R. China
| | - Renchao Zhang
- Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, P.R. China
| | - Zhiwei Zhou
- Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P.R. China
| | - Zhaohui Zhu
- Department of Nuclear Medicine, Peiking Union Medical College Hospital, Beijing, P.R. China
| | - Chenghao Shao
- Department of General Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, P.R. China
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Iwasaki M, Tsuchida K, Jinnai H, Komatsubara T, Arisaka T, Tsunemi M, Nakano M, Iijima M, Hiraishi H. Multimodal Treatment of Vasoactive Intestinal Polypeptide-producing Pancreatic Neuroendocrine Tumors with Liver Metastases. Intern Med 2017; 56:517-522. [PMID: 28250297 PMCID: PMC5399202 DOI: 10.2169/internalmedicine.56.7512] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
A 53-year-old man presented with diarrhoea and hypokalaemia and was diagnosed with a neuroendocrine tumour of unknown origin with multiple liver metastases. Somatostatin analogues led to a reduction in the size of the tumours and improvement of his symptoms. However, after several years, the tumours grew in size, and the patient's clinical symptoms recurred. The patient underwent transcatheter arterial embolization (TAE) of the hepatic artery to treat the liver metastases. Immediately after embolization, the symptoms disappeared. Although the patient had an unresectable vasoactive intestinal polypeptide-producing neuroendocrine tumour, the endocrine symptoms were able to be controlled with chemotherapy and TAE, resulting in a long-term survival.
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Affiliation(s)
- Mari Iwasaki
- Department of Gastroenterology, Dokkyo Medical University, Japan
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Advances in the diagnosis and treatment of pancreatic neuroendocrine neoplasms in Japan. J Gastroenterol 2017; 52:9-18. [PMID: 27539256 DOI: 10.1007/s00535-016-1250-9] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Accepted: 07/27/2016] [Indexed: 02/06/2023]
Abstract
Several new developments have occurred in the field of pancreatic neuroendocrine neoplasm (PNEN) recently in Japan. First, the utility of chromogranin A (CgA), useful for the diagnosis and monitoring of the treatment response of neuroendocrine neoplasm (NEN), has been demonstrated in Japan. For PNEN diagnosis and treatment, grading and correct histological diagnosis according to the WHO 2010 classification is important. Regarding the histological diagnosis, the advent of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has enabled correct pathological diagnosis and suitable treatment for the affected tissue. Furthermore, EUS-FNA has also facilitates the assessment of the presence or absence of gene mutations. In addition, patients who have a well-differentiated neuroendocrine tumor (NET) showing a Ki-67 index of higher than 20 % according to the WHO 2010 classification, have also been identified, and their responses to treatment were found to be different from those of patients with poorly differentiated neuroendocrine carcinoma (NEC). Therefore, the concept of NET G3 was proposed. Additionally, somatostatin receptor type 2 is expressed in several cases of NET, and somatostatin receptor scintigraphy (111In-octreoscan) has also been approved in Japan. This advancement will undoubtedly contribute to the localization diagnosis, the identification of remote metastasis, and assessments of the treatment responses of PNEN. Finally, regarding the treatment strategy for PNEN, the management of liver metastasis is important. The advent of novel molecular-targeted agents has dramatically improved the prognosis of advanced PNEN. Multimodality therapy that accounts for the tumor stage, degree of tumor differentiation, tumor volume, and speed of tumor growth is required.
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Fujimori N, Osoegawa T, Lee L, Tachibana Y, Aso A, Kubo H, Kawabe K, Igarashi H, Nakamura K, Oda Y, Ito T. Efficacy of endoscopic ultrasonography and endoscopic ultrasonography-guided fine-needle aspiration for the diagnosis and grading of pancreatic neuroendocrine tumors. Scand J Gastroenterol 2016; 51:245-52. [PMID: 26513346 DOI: 10.3109/00365521.2015.1083050] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIM Pancreatic neuroendocrine tumors (pNETs) are histologically categorized according to the WHO 2010 classification by their mitotic index or Ki-67 index as G1, G2, or G3. The present study examined the efficacy of endoscopic ultrasonography (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) in the diagnosis and grading of pNET. METHODS We retrospectively reviewed 61 pNETs in 51 patients who underwent EUS between January 2007 and June 2014. All lesions were pathologically diagnosed by surgical resection or EUS-FNA. We evaluated the detection rates of EUS for pNET and sensitivity of EUS-FNA, and compared the Ki-67 index between EUS-FNA samples and surgical specimens. EUS findings were compared between G1 and G2/G3 tumors. RESULTS EUS showed significantly higher sensitivity (96.7%) for identifying pNET than CT (85.2%), MRI (70.2%), and ultrasonography (75.5%). The sensitivity of EUS-FNA for the diagnosis of pNET was 89.2%. The concordance rate of WHO classification between EUS-FNA and surgical specimens was 69.2% (9/13). The concordance rate was relatively high (87.5%, 5/6) in tumors <20 mm but lower (57.1%; 4/7) in tumors ≥20 mm. Regarding EUS findings, G2/G3 tumors were more likely to be large (>20 mm), heterogeneous, and have main pancreatic duct (MPD) obstruction than G1 tumors. Multivariate analysis showed large diameter and MPD obstruction were significantly associated with G2/G3 tumors. CONCLUSIONS EUS and EUS-FNA are highly sensitive and accurate diagnostic methods for pNET. Characteristic EUS findings such as large tumor size and MPD obstruction are suggestive of G2/G3 tumors and would be helpful for grading pNETs.
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Affiliation(s)
- Nao Fujimori
- a Department of Medicine and Bioregulatory Science , Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan .,b Department of Gastroenterology , Clinical Research Institute, National Hospital Organization Kyushu Medical Center , Fukuoka , Japan , and
| | - Takashi Osoegawa
- a Department of Medicine and Bioregulatory Science , Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan
| | - Lingaku Lee
- a Department of Medicine and Bioregulatory Science , Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan
| | - Yuichi Tachibana
- a Department of Medicine and Bioregulatory Science , Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan
| | - Akira Aso
- a Department of Medicine and Bioregulatory Science , Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan
| | - Hiroaki Kubo
- a Department of Medicine and Bioregulatory Science , Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan
| | - Ken Kawabe
- a Department of Medicine and Bioregulatory Science , Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan .,b Department of Gastroenterology , Clinical Research Institute, National Hospital Organization Kyushu Medical Center , Fukuoka , Japan , and
| | - Hisato Igarashi
- a Department of Medicine and Bioregulatory Science , Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan
| | - Kazuhiko Nakamura
- a Department of Medicine and Bioregulatory Science , Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan
| | - Yoshinao Oda
- c Department of Anatomic Pathology , Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan
| | - Tetsuhide Ito
- a Department of Medicine and Bioregulatory Science , Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan
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Krishna SG, Bhattacharya A, Li F, Ross WA, Ladha H, Porter K, Atiq M, Bhutani MS, Lee JH. Diagnostic Differentiation of Pancreatic Neuroendocrine Tumor From Other Neoplastic Solid Pancreatic Lesions During Endoscopic Ultrasound-Guided Fine-Needle Aspiration. Pancreas 2016; 45:394-400. [PMID: 26418912 DOI: 10.1097/mpa.0000000000000488] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To identify factors differentiating pancreatic neuroendocrine tumors (PNETs) from non-PNET neoplastic solid pancreatic lesions (SPLs) and assess the accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). METHODS This is a retrospective study at a tertiary center of consecutive patients referred for EUS from 2004 to 2011. The main outcomes were pretest predictors and accuracy of EUS-FNA for diagnosis of PNET. RESULTS Among a total of 1108 EUS-FNAs for pancreatic lesions, 672 patients (PNET = 91, non-PNET neoplastic-SPLs = 581) had neoplastic-SPLs. The sensitivity, specificity, and accuracy of EUS-FNA for diagnosis of PNETs were 98.9%, 100%, and 99.9%, respectively. The mean needle-passes were 3.0/patient. The EUS volume (mean/year per endosonographer) in preceding 3 years significantly correlated with fewer needle passes (rs: [-0.26]; P = 0.02).Multivariate analysis demonstrated that patients with PNET when compared to non-PNET neoplastic-SPLs were younger (odds ratio [OR], 3.23; 95% confidence interval [95% CI], 1.19-9.09; P = 0.001), have 2 or more pancreatic lesions (OR, 5.63; 95% CI, 1.74-18.2; P = 0.005), and lower CA 19-9 values (OR, 10.0; 95% CI, 3.13-33.3; P = 0.001). Further, PNETs were less likely to have weight loss (OR, 0.40; 95% CI, 0.17-0.90; P = 0.03), current smoking (OR, 0.47; 95% CI, 0.22-0.98; P < 0.05), pancreatic ductal dilation (OR, 0.28; 95% CI, 0.13-0.60; P = 0.002), or imaging evidence of arterial invasion (OR, 0.22; 95% CI, 0.07-0.71; P = 0.01). CONCLUSIONS Although pre-FNA findings can reliably characterize, EUS-FNA is highly accurate for the diagnosis of PNETs.
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Affiliation(s)
- Somashekar G Krishna
- From the *Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX; †Department of Gastroenterology, Hepatology, and Nutrition, and ‡Department of Biostatistics, The Ohio State University, Columbus, OH
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Eloubeidi MA, Decker GA, Chandrasekhara V, Chathadi KV, Early DS, Evans JA, Fanelli RD, Fisher DA, Foley K, Hwang JH, Jue TL, Lightdale JR, Pasha SF, Saltzman JR, Sharaf R, Shergill AK, Cash BD, DeWitt JM. The role of endoscopy in the evaluation and management of patients with solid pancreatic neoplasia. Gastrointest Endosc 2016; 83:17-28. [PMID: 26706297 DOI: 10.1016/j.gie.2015.09.009] [Citation(s) in RCA: 87] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023]
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Hijioka S, Hara K, Mizuno N, Imaoka H, Bhatia V, Mekky MA, Yoshimura K, Yoshida T, Okuno N, Hieda N, Tajika M, Tanaka T, Ishihara M, Yatabe Y, Shimizu Y, Niwa Y, Yamao K. Diagnostic performance and factors influencing the accuracy of EUS-FNA of pancreatic neuroendocrine neoplasms. J Gastroenterol 2016; 51:923-30. [PMID: 26768605 PMCID: PMC4990623 DOI: 10.1007/s00535-016-1164-6] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Accepted: 12/24/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND Multiple studies have investigated sampling adequacy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for pancreatic neuroendocrine neoplasms (pNENs). However, none have described the diagnostic performance of EUS-FNA for pNENs, or the influencing factors. The aim of this study was to evaluate the diagnostic accuracy of EUS-FNA, with post-operative pathological diagnosis as the gold standard, and factors predictive of inadequate EUS sampling. METHODS From 1998 to 2014, a total of 698 patients underwent pancreatic resection and 1455 patients underwent EUS-FNA sampling for pancreatic lesions. A total of 410 cases underwent both surgical resection and preceding EUS-FNA. Of these, 60 cases (49 true pNEN, nine non-diagnostic, two misdiagnoses) were included. We studied diagnostic performance of EUS-FNA and factors that were associated with failed diagnosis. RESULTS Of the 60 cases, EUS-FNA yield was 49 true-positive cases, two misdiagnoses, and nine non-diagnostic cases (including six suggestive cases). Sensitivity, specificity, and accuracy were 84.5, 99.4, and 97.3 %, respectively; including the six suggestive cases, diagnostic values were 94.8 % sensitivity (55/58), 99.4 % specificity (350/352), and 98.7 % accuracy (405/410). In multivariate analysis, sampling adequacy rates were significantly lower when lesions were located in the pancreatic head [odds ratio (OR) = 10.0] and in tumor-rich stromal fibrosis (OR = 10.45). Tumor size, needle type, tumor grading, presence of cystic component, and time period were not significant factors. CONCLUSIONS EUS-FNA offers high accuracy for pNEN. However, location of the tumor in the pancreatic head and presence of rich stromal fibrosis negatively impacts sampling adequacy.
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Affiliation(s)
- Susumu Hijioka
- Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
| | - Kazuo Hara
- Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan
| | - Nobumasa Mizuno
- Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan
| | - Hiroshi Imaoka
- Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan
| | - Vikram Bhatia
- Department of Gastroenterology, Fortis Escorts Liver and Digestive Institute, New Delhi, India
| | - Mohamed A Mekky
- Department of Tropical Medicine and Gastroenterology, Assiut University Hospital, Assiut, Egypt
| | - Kenichi Yoshimura
- Innovative Clinical Research Center, Kanazawa University, Kanazawa, Japan
| | - Tsukasa Yoshida
- Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan
| | - Nozomi Okuno
- Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan
| | - Nobuhiro Hieda
- Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan
| | - Masahiro Tajika
- Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Tsutomu Tanaka
- Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Makoto Ishihara
- Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Yasushi Yatabe
- Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Yasuhiro Shimizu
- Department of Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Yasumasa Niwa
- Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Kenji Yamao
- Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan
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James PD, Tsolakis AV, Zhang M, Belletrutti PJ, Mohamed R, Roberts DJ, Heitman SJ. Incremental benefit of preoperative EUS for the detection of pancreatic neuroendocrine tumors: a meta-analysis. Gastrointest Endosc 2015; 81:848-56.e1. [PMID: 25805462 DOI: 10.1016/j.gie.2014.12.031] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2014] [Accepted: 12/01/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND Current guidelines recommend CT scan or magnetic resonance imaging as the initial imaging modalities for the work-up of suspected pancreatic neuroendocrine tumors (PNETs). OBJECTIVE To determine the incremental benefit of preoperative EUS (IBEUS) for the detection of suspected PNETs after other investigative modalities have been attempted. DESIGN This systematic review searched MEDLINE, EMBASE, bibliographies of included articles, and conference proceedings for studies reporting original data regarding the preoperative detection of PNETs. Pooled IBEUS was calculated by using random effects models. Heterogeneity was explored by using stratified meta-analysis and meta-regression. Evidence of small-study effects was assessed by using funnel plots and the Begg test. PATIENTS Patients with suspected PNETs. INTERVENTIONS EUS evaluation. MAIN OUTCOME MEASUREMENTS The pooled IBEUS for the detection of PNETs after CT scan, with or without additional investigative modalities. RESULTS Among 4505 citations identified, we included 17 cohort studies (612 patients). EUS identified PNETs in 97% of cases. Improved PNET identification with EUS was observed in all of the studies. After adjusting for small-study effects, meta-analysis showed that EUS alone could identify PNETs in approximately 1 in 4 patients (adjusted IBEUS 26%; 95% confidence interval, 17%-37%). The pooled IBEUS varied based on the study design, study size, type of CT scan used, and the number of modalities used prior to EUS. LIMITATIONS The majority of included studies were retrospective. Small-study effects were observed. CONCLUSION Preoperative EUS is associated with an increase in PNET detection after other modalities are attempted.
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Affiliation(s)
- Paul D James
- Department of Medicine and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada; Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Apostolos V Tsolakis
- Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; Department of Medical Sciences, Section of Endocrine Oncology, Uppsala University, Uppsala, Sweden
| | - Mei Zhang
- Department of Medical Sciences, Section of Endocrine Oncology, Uppsala University, Uppsala, Sweden
| | - Paul J Belletrutti
- Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Rachid Mohamed
- Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Derek J Roberts
- Department of Surgery and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Steven J Heitman
- Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
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Tomimaru Y, Eguchi H, Tatsumi M, Kim T, Hama N, Wada H, Kawamoto K, Kobayashi S, Morii E, Mori M, Doki Y, Nagano H. Clinical utility of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in predicting World Health Organization grade in pancreatic neuroendocrine tumors. Surgery 2015; 157:269-76. [DOI: 10.1016/j.surg.2014.09.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2014] [Accepted: 09/10/2014] [Indexed: 12/20/2022]
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Singh S, Dey C, Kennecke H, Kocha W, Maroun J, Metrakos P, Mukhtar T, Pasieka J, Rayson D, Rowsell C, Sideris L, Wong R, Law C. Consensus Recommendations for the Diagnosis and Management of Pancreatic Neuroendocrine Tumors: Guidelines from a Canadian National Expert Group. Ann Surg Oncol 2014; 22:2685-99. [PMID: 25366583 DOI: 10.1245/s10434-014-4145-0] [Citation(s) in RCA: 70] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2014] [Indexed: 12/29/2022]
Abstract
Pancreatic neuroendocrine tumors (pNETs) are rare heterogeneous tumors that have been steadily increasing in both incidence and prevalence during the past few decades. Pancreatic NETs are categorized as functional (F) or nonfunctional (NF) based on their ability to secrete hormones that elicit clinically relevant symptoms. Specialized diagnostic tests are required for diagnosis. Treatment options are diverse and include surgical resection, intraarterial hepatic therapy, and peptide receptor radionuclide therapy (PRRT). Systemic therapy options include targeted agents as well as chemotherapy when indicated. Diagnosis and management should occur through a collaborative team of health care practitioners well-experienced in managing pNETs. Recent advances in pNET treatment options have led to the development of the Canadian consensus document described in this report. The discussion includes the epidemiology, classification, pathology, clinical presentation and prognosis, imaging and laboratory testing, medical and surgical management, and recommended treatment algorithms for pancreatic neuroendocrine cancers.
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Affiliation(s)
- Simron Singh
- Department of Medicine, Odette Cancer Centre - Sunnybrook Hospital, University of Toronto, Toronto, ON, Canada,
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Abstract
Pancreatic neuroendocrine tumors (PNETs) are rare pancreatic neoplasms comprising only 1% to 2% of all pancreatic tumors. In recent years, the number of incidentally discovered PNETs has greatly increased given the widespread use of axial imaging. However, a significant proportion of PNETs may not be visualized on conventional imaging such as computed tomography, magnetic resonance imaging, and somatostatin receptor scintigraphy. Endoscopic ultrasound (EUS) has become an integral part of the diagnosis of PNETs because of its high sensitivity for detecting, localizing, and diagnosing PNETs. EUS-guided tissue acquisition provides histologic and immunologic confirmation, and may also allow prognostication about tumor behavior. In addition to preoperative assessment of these tumors, EUS has also been shown to have an important role in nonoperative management of small nonfunctional PNETs. Finally, recent developments suggest that interventional EUS may be used to aid intraoperative localization of PNETs and to deliver therapeutic agents for the treatment of PNETs. This review will discuss the endoscopic diagnosis and treatment of PNETs, with focus on recent advances in the utility of EUS in the clinical management of these tumors.
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Unno J, Kanno A, Masamune A, Kasajima A, Fujishima F, Ishida K, Hamada S, Kume K, Kikuta K, Hirota M, Motoi F, Unno M, Shimosegawa T. The usefulness of endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of pancreatic neuroendocrine tumors based on the World Health Organization classification. Scand J Gastroenterol 2014; 49:1367-74. [PMID: 25180490 DOI: 10.3109/00365521.2014.934909] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND We assessed the controversial topic of using 22-gauge needles in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for the diagnosis and evaluation of Ki67 labeling indices (Ki67LI) of pancreatic neuroendocrine tumors (pNET). METHODS Thirty-eight patients with pNET who underwent EUS-FNA between January 1, 2008 and December 31, 2012 were enrolled in this study. When available, the Ki67LI and WHO classifications obtained by EUS-FNA and surgical resection were compared. RESULTS EUS-FNA with a 22-gauge needle acquired sufficient histological sample to correctly diagnose pNET in 35 cases (92.1%). Both EUS-FNA and surgical histological specimens were available for 19 cases, and grading classes of the 2 procedures were consistent in 17 cases (89.5%) according to the WHO classification based on the Ki67LI. Tumor size was associated with a difference in the Ki67LI between the 2 procedures, although the Ki67LI was almost completely consistent for tumors less than 18 mm in size. CONCLUSIONS EUS-FNA with a 22-gauge needle is a safe and highly accurate technique for the diagnosis of pNET. There was a clear correlation between the Ki67LI of histological specimens acquired by EUS-FNA and surgery. EUS-FNA with a 22-gauge needle is useful to predict the WHO classification of pNET.
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Affiliation(s)
- Jun Unno
- Division of Gastroenterology, Tohoku University Graduate School of Medicine , Sendai , Japan
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Grimaldi F, Fazio N, Attanasio R, Frasoldati A, Papini E, Angelini F, Baldelli R, Berretti D, Bianchetti S, Bizzarri G, Caputo M, Castello R, Cremonini N, Crescenzi A, Davì MV, D’Elia AV, Faggiano A, Pizzolitto S, Versari A, Zini M, Rindi G, Öberg K. Italian Association of Clinical Endocrinologists (AME) position statement: a stepwise clinical approach to the diagnosis of gastroenteropancreatic neuroendocrine neoplasms. J Endocrinol Invest 2014; 37:875-909. [PMID: 25038902 PMCID: PMC4159596 DOI: 10.1007/s40618-014-0119-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2014] [Accepted: 03/29/2014] [Indexed: 02/07/2023]
Affiliation(s)
- Franco Grimaldi
- Endocrinology and Metabolic Disease Unit, Azienda Ospedaliero-Universitaria “S. Maria della Misericordia”, P.le S.M. della Misericordia, 15-33100, Udine, Italy
| | - Nicola Fazio
- Unit of Gastrointestinal and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy
| | | | - Andrea Frasoldati
- Endocrinology Unit, Arcispedale S. Maria Nuova IRCCS, Reggio Emilia, Italy
| | - Enrico Papini
- Endocrinology Unit, Regina Apostolorum Hospital, Albano Laziale, Rome, Italy
| | - Francesco Angelini
- Oncology and Hematology Unit, Regina Apostolorum Hospital, Albano Laziale, Rome, Italy
| | - Roberto Baldelli
- Endocrinology Section, Regina Elena National Cancer Institute, Rome, Italy
| | - Debora Berretti
- Gastroenterology Unit, Azienda Ospedaliero-Universitaria “S. Maria della Misericordia”, Udine, Italy
| | - Sara Bianchetti
- Oncology and Hematology Unit, Regina Apostolorum Hospital, Albano Laziale, Rome, Italy
| | - Giancarlo Bizzarri
- Diagnostic Imaging Unit, Regina Apostolorum Hospital, Albano Laziale, Rome, Italy
| | - Marco Caputo
- Dipartimento Servizi di Diagnosi e Cura, AUSL 22 Regione Veneto, Bussolengo, VR Italy
| | - Roberto Castello
- Medicina Interna ad indirizzo Endocrinologico, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
| | - Nadia Cremonini
- Endocrinology Unit, Maggiore and Bellaria Hospital, Bologna, Italy
| | - Anna Crescenzi
- Pathology Unit, Regina Apostolorum Hospital, Albano Laziale, Rome, Italy
| | - Maria Vittoria Davì
- Medicina Interna D, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
| | - Angela Valentina D’Elia
- Genetic Service, Azienda Ospedaliero-Universitaria “S. Maria della Misericordia”, Udine, Italy
| | - Antongiulio Faggiano
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Stefano Pizzolitto
- Pathology Unit, Azienda Ospedaliero-Universitaria “S. Maria della Misericordia”, Udine, Italy
| | - Annibale Versari
- Nuclear Medicine Service, Arcispedale S. Maria Nuova IRCCS, Reggio Emilia, Italy
| | - Michele Zini
- Endocrinology Unit, Arcispedale S. Maria Nuova IRCCS, Reggio Emilia, Italy
| | - Guido Rindi
- Institute of Pathology, Policlinico A. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Kjell Öberg
- Department of Endocrine Oncology, University Hospital, Uppsala, Sweden
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Koh YX, Chok AY, Zheng HL, Tan CS, Goh BKP. A systematic review and meta-analysis of the clinicopathologic characteristics of cystic versus solid pancreatic neuroendocrine neoplasms. Surgery 2014; 156:83-96.e2. [PMID: 24878455 DOI: 10.1016/j.surg.2014.03.026] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Accepted: 03/11/2014] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Cystic pancreatic neuroendocrine neoplasms (PNENs) are rare neoplasms, and presently, it is uncertain whether their behavior is similar or distinct from their solid counterparts. This study aimed to review systematically the present literature to compare the clinicopathologic characteristics of cystic PNENs versus their solid counterparts to determine whether cystic PNENs are likely to be a distinct entity from solid PNENs. METHODS Comparative studies of solid versus cystic PNENs studies were reviewed. Cystic and solid PNENs were compared on the basis of several clinicopathologic characteristics. RESULTS Seven nonrandomized case control studies compared 152 cystic versus 915 solid PNENs. Pooled analysis demonstrated that the likelihood of PNENs to be located in the head/uncinate of the pancreas was lower for cystic than solid neoplasms (27.7% vs 45.5%, odds ratio [OR] 0.452, 95% confidence interval [95% CI] 0.304-0.673, P < .001). Cystic PNENs were less likely to be functional (14% vs 24.4%, OR 0.405, 95% CI 0.221-0.742, P = .003) and were more likely to be benign/uncertain rather than malignant compared with solid PNENs (90.3% vs 65.9%, OR 3.151, 95% CI 1.297-7.652, P = .011). Cystic PNENs were more likely to have a mitotic count <2 per 10 hpf and a Ki67 index <2% (93.3% vs 72.7%, OR 4.897, 95% CI 2.139-11.209, P < .001 and 82.4% vs 54.1%, OR 4.079, 95% CI 2.177-7.641, P < .001), respectively. Cystic neoplasms were also less likely to have regional lymph node metastases than solid neoplasms (11.2% vs 28.9%, OR 0.387, 95% CI 0.219-0.685, P = .001).In this meta-analysis, there was no difference in the 5-year overall survival and 5-year disease-free survival between cystic vs solid PNENs (92.0% vs 86.8%, P .214) and (98.1% vs 83.9%, P = .185). CONCLUSION These findings suggest that cystic PNENs tend to be biologically less aggressive compared with their solid counterparts; more data, however, with respect to molecular analysis are required to establish whether cystic and solid PNENs were distinct pathologic entities.
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Affiliation(s)
- Ye-Xin Koh
- Division of Surgery, Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore
| | - Aik-Yong Chok
- Division of Surgery, Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore
| | - Hui-Li Zheng
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore
| | - Chuen-Seng Tan
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore
| | - Brian K P Goh
- Division of Surgery, Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore; Duke-NUS Graduate Medical School, Singapore.
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40
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Iglesias-Garcia J, Lariño-Noia J, Domínguez-Muñoz JE. When to puncture, when not to puncture: Pancreatic masses. Endosc Ultrasound 2014; 3:91-7. [PMID: 24955338 PMCID: PMC4064167 DOI: 10.4103/2303-9027.123007] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2013] [Accepted: 11/18/2013] [Indexed: 12/16/2022] Open
Abstract
Endoscopic ultrasound (EUS) has evolved to become a crucial tool for the evaluation of pancreatic diseases, among them solid pancreatic lesions. However, its ability to determine whether a lesion is malignant or not is difficult to establish based only in the endosonographic image. EUS-guided fine needle aspiration (EUS-FNA) allows obtaining a cytological and/or histological sample from pancreatic lesions, with a high overall accuracy and low complication rates. Although the clinical usefulness of EUS-FNA for pancreatic diseases is widely accepted, the indications for tissue diagnosis of pancreatic lesions suspected to be malignant is still controversial. This review highlights the diagnostic accuracy and complications of EUS-FNA, focusing on its current indications.
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Affiliation(s)
- Julio Iglesias-Garcia
- Gastroenterology Department, Foundation for Research in Digestive Diseases (FIENAD), University Hospital of Santiago de Compostela, Spain
| | - Jose Lariño-Noia
- Gastroenterology Department, Foundation for Research in Digestive Diseases (FIENAD), University Hospital of Santiago de Compostela, Spain
| | - J Enrique Domínguez-Muñoz
- Gastroenterology Department, Foundation for Research in Digestive Diseases (FIENAD), University Hospital of Santiago de Compostela, Spain
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41
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Enestvedt BK, Ahmad N. To cease or 'de-cyst'? The evaluation and management of pancreatic cystic lesions. Curr Gastroenterol Rep 2014; 15:348. [PMID: 24014118 DOI: 10.1007/s11894-013-0348-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Due to the widespread use of cross-sectional imaging and advances in imaging technology, pancreatic cystic lesions are increasingly being detected. The diagnosis and management of such cysts remains challenging and continues to evolve. Different pancreatic cyst types have varying malignant potential. Thus, accurate cyst characterization is essential to appropriate management; the most clinically important distinction is differentiating mucinous lesions, which have malignant potential and may benefit from surgical resection, from non-mucinous cystic lesions. Endoscopic ultrasound with fine needle aspiration with cytologic, chemical,, and tumor marker analysis appears to be the best currently available method for accurately characterizing a cyst's malignant potential, and therefore impacts the most important management decision for a pancreatic cyst-continued surveillance or surgical resection.
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Affiliation(s)
- Brintha K Enestvedt
- Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, L461, Portland, OR 97239, USA.
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42
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van Essen M, Sundin A, Krenning EP, Kwekkeboom DJ. Neuroendocrine tumours: the role of imaging for diagnosis and therapy. Nat Rev Endocrinol 2014; 10:102-14. [PMID: 24322649 DOI: 10.1038/nrendo.2013.246] [Citation(s) in RCA: 102] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
In patients with neuroendocrine tumours (NETs), a combination of morphological imaging and nuclear medicine techniques is mandatory for primary tumour visualization, staging and evaluation of somatostatin receptor status. CT and MRI are well-suited for discerning small lesions that might escape detection by single photon emission tomography (SPECT) or PET, as well as for assessing the local invasiveness of the tumour or the response to therapy. Somatostatin receptor imaging, by (111)In-pentetreotide scintigraphy or PET with (68)Ga-labelled somatostatin analogues, frequently identifies additional lesions that are not visible on CT or MRI scans. Currently, somatostatin receptor scintigraphy with (111)In-pentetreotide is the more frequently available of the two techniques to determine somatostatin receptor expression and is needed to select patients for peptide receptor radionuclide therapy. In the future, because of its higher sensitivity, PET with (68)Ga-labelled somatostatin analogues is expected to replace somatostatin receptor scintigraphy. Whereas (18)F-FDG-PET is only used in high-grade neuroendocrine cancers, PET-CT with (18)F-dihydroxy-L-phenylalanine or (11)C-5-hydroxy-L-tryptophan is a useful problem-solving tool and could be considered for the evaluation of therapy response in the future. This article reviews the role of imaging for the diagnosis and management of intestinal and pancreatic NETs. Response evaluation and controversies in NET imaging will also be discussed.
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Affiliation(s)
- Martijn van Essen
- Department of Nuclear Medicine, Erasmus MC, 's Gravendijkwal 230, Rotterdam, 3015 GD, Netherlands
| | - Anders Sundin
- Department of Radiology, Karolinska University Hospital, Stockholm, 17176 Stockholm, Sweden
| | - Eric P Krenning
- Department of Nuclear Medicine, Erasmus MC, 's Gravendijkwal 230, Rotterdam, 3015 GD, Netherlands
| | - Dik J Kwekkeboom
- Department of Nuclear Medicine, Erasmus MC, 's Gravendijkwal 230, Rotterdam, 3015 GD, Netherlands
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Eisendrath P, Ibrahim M. How good is fine needle aspiration? What results should you expect? Endosc Ultrasound 2014; 3:3-11. [PMID: 24949404 PMCID: PMC4063262 DOI: 10.4103/2303-9027.127122] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2013] [Accepted: 01/03/2014] [Indexed: 12/11/2022] Open
Abstract
Tissue acquisition plays a key role before treatment decision in most of oncological pathologies but also in several benign diseases. By offering tissue sampling, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become an essential tool in the diagnostic processes. One of the reasons for the success of the technique is related to its excellent diagnostic performance. The diagnostic accuracy of EUS-FNA is above 80% for most of the usual indications. These performances are however dependent on some factors related to both the disease and patient's medical history but also related to medical staff expertise. Endoscopist needs to know how to reach a lesion but also how to efficiently acquire good tissue samples. This review aims to report general recommendations available in the literature for high quality EUS-FNA. Sample processing and sample interpretation also influence diagnostic accuracy of FNA. This paper includes a discussion on sample processing and benefits of the on-site pathology examination. It also provides the results reported in the literature of sample adequacy and diagnostic performance of EUS-FNA for most common indications: Pancreatic diseases, sub-mucosal lesion, mucosal thickenings, lymph nodes, cystic lesion and free fluids.
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Affiliation(s)
- Pierre Eisendrath
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme Hospital, Université Libre de Bruxelles, 808 Route de Lennik, B 1070 Brussels, Belgium
| | - Mostafa Ibrahim
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme Hospital, Université Libre de Bruxelles, 808 Route de Lennik, B 1070 Brussels, Belgium
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Attili F, Capurso G, Vanella G, Fuccio L, Delle Fave G, Costamagna G, Larghi A. Diagnostic and therapeutic role of endoscopy in gastroenteropancreatic neuroendocrine neoplasms. Dig Liver Dis 2014; 46:9-17. [PMID: 23731843 DOI: 10.1016/j.dld.2013.04.007] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2013] [Accepted: 04/20/2013] [Indexed: 02/08/2023]
Abstract
Gastroenteropancreatic neuroendocrine neoplasms have substantially increased over the last decades. Because of the indolent clinical course of the disease even in advance stages and the rise in the incidental diagnosis of small asymptomatic lesions, the prevalence of gastroenteropancreatic neuroendocrine neoplasms is higher than that of pancreatic, gastric and oesophageal adenocarcinomas, making them the second most prevalent cancer type of the gastrointestinal tract. This increase in the overall prevalence of gastroenteropancreatic neuroendocrine neoplasms has been paralleled by a growth in the importance of the endoscopist in the care of these patients, who usually require a multidisciplinary approach. In this manuscript the diagnostic and therapeutic role of endoscopic for gastroenteropancreatic neuroendocrine neoplasms will be reviewed.
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Affiliation(s)
- Fabia Attili
- Digestive Endoscopy Unit, Catholic University, Rome, Italy
| | - Gabriele Capurso
- Division of Digestive and Liver Disease, University La Sapienza, Rome, Italy
| | | | - Lorenzo Fuccio
- Division of Gastroenterology, S. Orsola-Malpighi Hospital, University of Bologna, Italy
| | | | | | - Alberto Larghi
- Digestive Endoscopy Unit, Catholic University, Rome, Italy.
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Weynand B, Borbath I, Bernard V, Sempoux C, Gigot JF, Hubert C, Lannoy V, Deprez PH, Jouret-Mourin A. Pancreatic neuroendocrine tumour grading on endoscopic ultrasound-guided fine needle aspiration: high reproducibility and inter-observer agreement of the Ki-67 labelling index. Cytopathology 2013; 25:389-95. [PMID: 24750272 DOI: 10.1111/cyt.12111] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/25/2013] [Indexed: 12/30/2022]
Abstract
OBJECTIVES Assessment of proliferation by the Ki-67 labelling index (Ki67-LI) is an important parameter of pancreatic neuroendocrine tumour (pNET) prognosis on resection specimens. Ki67-LI values for grading are not fully established on endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). The aim of the study was to determine the accuracy of Ki67-LI on EUS-FNA to predict a final grade of pNET and to analyse the relationship between cytological grading and progression-free survival (PFS). METHODS Between 1996 and 2010, 46 pNETs (33 were resected) from 45 patients were diagnosed by EUS-FNA. Ki67-LI was evaluated on cytological and histological material for each tumour and classified according to the 2010 WHO grading system. RESULTS A very good inter-observer agreement for Ki67-LI on EUS-FNA and surgical specimens, respectively, were obtained. Discrepancies were observed between histology and cytology, especially in grade 2 (G2) tumours, where cytology underestimated grading owing to tumour heterogeneity. Still, EUS-FNA was able to distinguish a poor prognostic group, as the actuarial PFS of cytological (c) G3 tumours was 10 ± 4 months versus 29 ± 7 and 68 ± 10 for cG2 and cG1 tumours, respectively (P < 0.0001). CONCLUSION This study attests the reproducibility of Ki67-LI of pNETs whether counted on cytology or histology with a very good inter-observer correlation. Determination of Ki67-LI on EUS-FNA of pNETs should be included systematically in their prognostic work-up.
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Affiliation(s)
- B Weynand
- Department of Pathology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
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Abstract
Pancreatic neuroendocrine tumors (PanNETs) have increased in incidence in the USA over the last 20 years. Although PanNETs are often misconceived as being indolent tumors as they have a far more favorable prognosis over pancreatic adenocarcinoma, roughly 60-70% of patients have metastatic disease at the time of diagnosis due to presentation late in the disease process. While improvements in imaging modalities allow for early detection and better tumor localization, recent advancements in basic science, as well as surgical and medical management of PanNETs have further improved the prognosis. The mainstay of therapy for localized PanNETs is surgical intervention, which has become safer and is slowly shifting towards a more minimally invasive approach. However, the prognosis still remains relatively bleak for patients with unresectable disease. Fortunately, novel molecular targeted therapies, such as everolimus and sunitinib, have recently come into the limelight and have shown significant promise for the treatment of locally advanced and metastatic disease.
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Affiliation(s)
- Miral R Sadaria
- Department of Surgery, University of Colorado Anschutz Medical Campus, Division of GI, Tumor and Endocrine Surgery, Academic Office One, 12631 East 17th Avenue, C311, Aurora, CO 80045, USA
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47
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Incidental neuroendocrine tumors of the pancreas: MDCT findings and features of malignancy. AJR Am J Roentgenol 2013; 200:355-62. [PMID: 23345357 DOI: 10.2214/ajr.11.8037] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE The objective of our study was to evaluate the MDCT features of incidentally detected neuroendocrine tumors (NETs) of the pancreas, identify features that can predict tumor biology or aggressiveness and long-term outcome, and determine the incidence of "nonbenign" behavior. MATERIALS AND METHODS In this retrospective study, 60 histologically verified pancreatic NETs incidentally detected with contrast-enhanced MDCT were included. Various MDCT features such as size, morphology, enhancement, and presence of calcifications were evaluated and were correlated with tumor biology on histopathology. The sensitivity, specificity, predictive values, and accuracy were calculated for MDCT features in predicting nonbenign biology and risk of recurrence. RESULTS A total of 32 of 60 (53%) NETs were nonbenign: most were large (mean, 29.1 mm) with a solid or complex pattern. NET size of 3 cm or larger yielded a positive predictive value of 61% for nonbenign tumors and 100% when calcification was present. In 12 patients with recurrence, 92% of NETs were nonbenign. The presence of calcification, local invasion, main pancreatic duct dilatation, vascular invasion, and lymph node enlargement along with angioinvasion and a Ki-67 index greater than 2% on histology were associated with a nonbenign diagnosis and a higher risk of recurrence. CONCLUSION Approximately 50% of incidental NETs show uncertain or malignant behavior. Solid tumors 3 cm or larger are commonly nonbenign; however, about 30% of tumors smaller than that size cutoff can be malignant. Nonbenign tumors and those with invasive features on MDCT have a higher incidence of recurrence.
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Samad A, Attam R, Jessurun J, Pambuccian SE. Psammoma bodies and abundant stromal amyloid in an endoscopic ultrasound guided fine needle aspirate (EUS-FNA) of a pancreatic neuroendocrine tumor: a potential pitfall. Diagn Cytopathol 2013; 42:766-71. [PMID: 23447372 DOI: 10.1002/dc.22975] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2012] [Revised: 12/01/2012] [Accepted: 01/01/2013] [Indexed: 11/11/2022]
Affiliation(s)
- Arbaz Samad
- Department of Laboratory Medicine and Pathology, and Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota
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Shrikhande SV, Sirohi B, Goel M, Barreto SG. Pancreatic neuroendocrine tumors. Indian J Gastroenterol 2013; 32:3-17. [PMID: 23054950 DOI: 10.1007/s12664-012-0257-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2012] [Accepted: 09/04/2012] [Indexed: 02/04/2023]
Abstract
Pancreatic neuroendocrine tumors (pancreatic NETs) are rare, low- to intermediate-grade neoplasms thought to arise from the pancreatic islets. Recent advances in pathology and our understanding of the biological behavior of this group of tumors has resulted in changes in their nomenclature and how we treat them. This review puts into perspective our current understanding of pancreatic NETs in terms of their incidence, pathology, and management.
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Affiliation(s)
- Shailesh V Shrikhande
- Gastrointestinal and Hepato-Pancreato-Biliary Surgical Oncology, Tata Memorial Centre, Ernest Borges Marg, Parel, Mumbai, India.
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50
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Tharian B, Tsiopoulos F, George N, Pietro SD, Attili F, Larghi A. Endoscopic ultrasound fine needle aspiration: Technique and applications in clinical practice. World J Gastrointest Endosc 2012; 4:532-44. [PMID: 23293723 PMCID: PMC3536850 DOI: 10.4253/wjge.v4.i12.532] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2011] [Revised: 11/09/2012] [Accepted: 12/01/2012] [Indexed: 02/05/2023] Open
Abstract
Since its initial report in 1992, endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has now been incorporated into the diagnostic and staging algorithm for the evaluation of benign and malignant diseases of the gastrointestinal tract and of adjacent organs. Its introduction constitutes a major breakthrough in the endoscopic field and has gradually transformed EUS from a pure imaging modality into a more interventional. In addition, the possibility of collecting samples, providing a definitive cytological and/or histological evidence of the presence of malignancy, has strongly contributed to changing EUS from a subjective, highly operator dependant procedure into a more objective one. This article will review the instrumentation, technique and the most important clinical applications of EUS-FNA.
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Affiliation(s)
- Benjamin Tharian
- Benjamin Tharian, Fotios Tsiopoulos, Nayana George, Salvatore Di Pietro, Fabia Attili, Alberto Larghi, Digestive Endoscopy Unit, Catholic University, 00168 Rome, Italy
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