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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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Song YJ, Lim JK, Choi JH. Role of endoscopic ultrasound in the diagnosis and local ablative therapy of pancreatic neuroendocrine tumors. Korean J Intern Med 2025; 40:170-180. [PMID: 39995262 PMCID: PMC11938681 DOI: 10.3904/kjim.2024.293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Revised: 11/05/2024] [Accepted: 11/14/2024] [Indexed: 02/26/2025] Open
Abstract
Advancements in diagnostic technology have led to the improved detection of pancreatic neuroendocrine tumors (PNETs) and thus to an increase in the number of reported cases. Endoscopic ultrasound (EUS) technology, including in combination with contrast-enhanced harmonic imaging, aids in distinguishing PNETs from other tumors, while EUS-guided fine-needle aspiration or biopsy has improved the histological diagnosis and grading of tumors. The recent introduction of EUS-guided ablation using ethanol injection or radiofrequency ablation has offered an alternative to surgery in the management of PNETs. Comparisons with surgery have shown similar outcomes but fewer adverse effects. Although standardized protocols and prospective studies with long-term follow-up are still needed, EUS-based methods are promising approaches that can contribute to a better quality of life for PNET patients.
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Affiliation(s)
- Yun Je Song
- Department of Internal Medicine, Dankook University Hospital, Dankook University College of Medicine, Cheonan, Korea
| | - Jun Kyeong Lim
- Department of Internal Medicine, Dankook University Hospital, Dankook University College of Medicine, Cheonan, Korea
| | - Jun-Ho Choi
- Department of Internal Medicine, Dankook University Hospital, Dankook University College of Medicine, Cheonan, Korea
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Monroe HL, El Naili R. Educational Case: Pancreatic neuroendocrine neoplasms. Acad Pathol 2025; 12:100161. [PMID: 40034114 PMCID: PMC11875812 DOI: 10.1016/j.acpath.2025.100161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 11/28/2024] [Accepted: 12/28/2024] [Indexed: 03/05/2025] Open
Affiliation(s)
- Hunter L. Monroe
- Department of Pathology, Anatomy and Laboratory Medicine, West Virginia University, Morgantown, WV, USA
| | - Reima El Naili
- Department of Pathology, Anatomy and Laboratory Medicine, West Virginia University, Morgantown, WV, USA
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Bakkaloglu IG, Gurbuz BC, Sahin O, Zemheri IE. Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Pancreatic Neuroendocrine Tumors with Rapid On-Site Evaluation: Single-Center Experience. Acta Cytol 2024; 69:122-130. [PMID: 39748620 DOI: 10.1159/000543364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 12/24/2024] [Indexed: 01/04/2025]
Abstract
INTRODUCTION Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a highly sensitive and accurate method for identifying pancreatic neuroendocrine tumors (PanNETs). However, research on grading and assessing the Ki67 proliferation index in FNA samples is limited. METHODS This study analyzed 335 EUS-FNA cases performed between 2016 and 2022, of which 12 cases of PanNET were further evaluated. The morphology, Ki-67 index, and grading (G) of cell blocks (CBs) obtained from the PanNET aspirations were compared to those of the resected material. RESULTS Out of 12 PanNET's with rapid on-site evaluation (ROSE), in FNA samples and CB, 7 (58.3%) cases were G1, while 5 (41.7%) cases were G2. On the other hand, on resection of these cases, 6 (50%) were diagnosed as G1, 5 (41.7%) cases were G2, and 1 case (8.3%) was G3. The average Ki-67 index in CB was 2.92 (min: 1 - max: 10), while in resections it was 4.67 (min: 1 - max: 22). Only 2 (16.6%) showed a discordance between grade and Ki-67, resulting in an overall concordance of over 80%. On average, 1.83 needle passes were made (range: 1-3), while the average number of slides and CBs were 9.33 (range: 1-24) and 2.17 (range: 1-6), respectively. There were no significant differences in the number of passes, slides, or CBs between the consistent and discordant groups. CONCLUSION Optimal counting techniques and sensitivity for Ki67 are crucial in grading PanNETs in both aspiration and resection materials. The grade and Ki-67 index demonstrated high concordance when comparing CB and resection. However, in low-volume centers, ROSE support can be beneficial in obtaining sufficient slides and CB for an adequate diagnosis.
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Affiliation(s)
| | - Begum Calim Gurbuz
- Pathology Department, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
| | - Onur Sahin
- Pathology Department, Health Sciences University, Umraniye Training and Research Hospital, Istanbul, Turkey
| | - Itir Ebru Zemheri
- Pathology Department, Health Sciences University, Umraniye Training and Research Hospital, Istanbul, Turkey
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Bispo M, Marques S, Fernandes A, Rodrigues-Pinto E, Vilas-Boas F, Rio-Tinto R, Devière J, on behalf of the Portuguese Pancreatic Club, specialized section of the Portuguese Society of Gastroenterology. Portuguese Pancreatic Club Perspective on the Surveillance Strategy for Pancreatic Neuroendocrine Tumours: When and How to Do It? GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2024; 31:306-313. [PMID: 39360175 PMCID: PMC11444664 DOI: 10.1159/000535815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 11/24/2023] [Indexed: 10/04/2024]
Abstract
Background Pancreatic neuroendocrine tumours (pNETs) are a highly heterogeneous group of tumours with widely variable biological behaviour. The incidence of pNETs has risen exponentially over the last three decades, particularly for asymptomatic small pNETs (≤2 cm), due to the widespread use of cross-sectional imaging in clinical practice. Summary Current consensus guidelines suggest that incidentally discovered pNETs ≤2 cm can be selectively followed due to the overall low risk of malignancy. Nevertheless, the "watch-and-wait" management strategy for small asymptomatic pNETs is still not widely accepted due to the lack of long-term data on the natural history of these small lesions. Additionally, it is clear that a subset of small pNETs may show malignant behaviour. Key Message Given the non-negligible risk of malignancy even in small pNETs, it is of the utmost importance to identify other preoperative factors, other than size, that may help to stratify the risk of malignant behaviour and guide clinical management. In this article, the Portuguese Pancreatic Club reviews the importance of risk stratification of pNETs and presents an updated perspective on the surveillance strategy for sporadic well-differentiated pNETs.
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Affiliation(s)
- Miguel Bispo
- Digestive Oncology Unit, Champalimaud Foundation, Lisbon, Portugal
| | - Susana Marques
- Digestive Oncology Unit, Champalimaud Foundation, Lisbon, Portugal
| | - Alexandra Fernandes
- Department of Gastroenterology, Centro Hospitalar de Leiria, Leiria, Portugal
| | - Eduardo Rodrigues-Pinto
- Department of Gastroenterology, Centro Hospitalar Universitário de São João, Porto, Portugal
- Faculty of Medicine of the University of Porto, Porto, Portugal
| | - Filipe Vilas-Boas
- Department of Gastroenterology, Centro Hospitalar Universitário de São João, Porto, Portugal
- Faculty of Medicine of the University of Porto, Porto, Portugal
| | | | - Jacques Devière
- Digestive Oncology Unit, Champalimaud Foundation, Lisbon, Portugal
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, Erasme University Hospital – Université Libre de Bruxelles, Brussels, Belgium
| | - on behalf of the Portuguese Pancreatic Club, specialized section of the Portuguese Society of Gastroenterology
- Digestive Oncology Unit, Champalimaud Foundation, Lisbon, Portugal
- Department of Gastroenterology, Centro Hospitalar de Leiria, Leiria, Portugal
- Department of Gastroenterology, Centro Hospitalar Universitário de São João, Porto, Portugal
- Faculty of Medicine of the University of Porto, Porto, Portugal
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, Erasme University Hospital – Université Libre de Bruxelles, Brussels, Belgium
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Massironi S, Franchina M, Ippolito D, Elisei F, Falco O, Maino C, Pagni F, Elvevi A, Guerra L, Invernizzi P. Improvements and future perspective in diagnostic tools for neuroendocrine neoplasms. Expert Rev Endocrinol Metab 2024; 19:349-366. [PMID: 38836602 DOI: 10.1080/17446651.2024.2363537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Accepted: 05/30/2024] [Indexed: 06/06/2024]
Abstract
INTRODUCTION Neuroendocrine neoplasms (NENs) represent a complex group of tumors arising from neuroendocrine cells, characterized by heterogeneous behavior and challenging diagnostics. Despite advancements in medical technology, NENs present a major challenge in early detection, often leading to delayed diagnosis and variable outcomes. This review aims to provide an in-depth analysis of current diagnostic methods as well as the evolving and future directions of diagnostic strategies for NENs. AREA COVERED The review extensively covers the evolution of diagnostic tools for NENs, from traditional imaging and biochemical tests to advanced genomic profiling and next-generation sequencing. The emerging role of technologies such as artificial intelligence, machine learning, and liquid biopsies could improve diagnostic precision, as could the integration of imaging modalities such as positron emission tomography (PET)/magnetic resonance imaging (MRI) hybrids and innovative radiotracers. EXPERT OPINION Despite progress, there is still a significant gap in the early diagnosis of NENs. Bridging this diagnostic gap and integrating advanced technologies and precision medicine are crucial to improving patient outcomes. However, challenges such as low clinical awareness, limited possibility of noninvasive diagnostic tools and funding limitations for rare diseases like NENs are acknowledged.
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Affiliation(s)
- Sara Massironi
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
- Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Marianna Franchina
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
| | - Davide Ippolito
- Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
- Department of Diagnostic Radiology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
| | - Federica Elisei
- Division of Nuclear Medicine, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
| | - Olga Falco
- Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Cesare Maino
- Department of Diagnostic Radiology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
| | - Fabio Pagni
- Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
- Division of Pathology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
| | - Alessandra Elvevi
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
| | - Luca Guerra
- Division of Nuclear Medicine, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
- Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
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Yamada M, Hara K, Mizuno N, Haba S, Kuwahara T, Okuno N, Kuraishi Y, Yanaidani T, Ishikawa S, Yasuda T, Fukui T. The role of needle-based confocal laser endomicroscopy in the diagnosis of pancreatic neuroendocrine tumors. Clin Endosc 2024; 57:393-401. [PMID: 37743070 PMCID: PMC11134000 DOI: 10.5946/ce.2023.068] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 04/18/2023] [Accepted: 04/19/2023] [Indexed: 09/26/2023] Open
Abstract
BACKGROUND/AIMS Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a highly accurate method for diagnosing pancreatic neuroendocrine tumors (PNETs); however, some PNETs are difficult to diagnose. Recently, the efficacy of needle-based confocal laser endomicroscopy (nCLE) in diagnosing solid pancreatic masses has been reported. However, the efficacy of nCLE in the diagnosis of PNETs remains unknown and only a small number of cases have been reported. Hence, this study aimed to evaluate the efficacy of nCLE in the diagnosis of PNETs. METHODS This single-center retrospective study evaluated 30 consecutive patients with suspected PNETs on contrast-enhanced computed tomography, who consented to nCLE combined with EUS-FNA and were diagnosed using EUS-FNA or surgical resection. The diagnostic criteria for PNETs using nCLE were based on the nesting and trabecular and glandular arrangement of tumor cell clusters surrounded by capillary vessels and fibrosis, as reported in previous studies. RESULTS The diagnosis using nCLE was classified into three categories: misdiagnosis in three cases (10%), non-diagnostic in six cases (20%), and diagnostic in 21 cases (70%). nCLE was able to diagnose PNET in one of the two cases with inconclusive EUS-FNA. CONCLUSIONS Although further development of the resolution and optimization of the diagnostic criteria are required, nCLE may constitute a useful diagnostic option in cases of inconclusive EUS-FNA for PNETs.
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Affiliation(s)
- Masanori Yamada
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Kazuo Hara
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Nobumasa Mizuno
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Shin Haba
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Takamichi Kuwahara
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Nozomi Okuno
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Yasuhiro Kuraishi
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Takafumi Yanaidani
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Sho Ishikawa
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Tsukasa Yasuda
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Toshitaka Fukui
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
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Notohara K, Nakamura K. Tissue processing of endoscopic ultrasound-guided fine-needle aspiration specimens from solid pancreatic lesions. J Med Ultrason (2001) 2024; 51:261-274. [PMID: 38051462 DOI: 10.1007/s10396-023-01387-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 10/04/2023] [Indexed: 12/07/2023]
Abstract
Now that tissue cores can be obtained using fine-needle biopsy (FNB) needles, the ways tissues are handled for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are changing. Direct smear, touch smear of core tissues, and centrifugation have been used for cytological examinations, and liquid-based cytology (LBC), which allows immunostaining and genetic tests that use residual samples, is emerging as an alternative. We emphasize that liquid cytology (Cytospin™ cytology and LBC) is still important, because it enables the diagnosis of pancreatic ductal adenocarcinoma (PDAC) when cancerous cells are scarce in specimens. Cell blocks are being replaced by core tissues obtained via FNB needles. Recent reports indicate that rapid on-site evaluation (ROSE) is not necessary when FNB needles are used, and macroscopic on-site evaluation is used to evaluate specimen adequacy. Macroscopic findings of specimens are helpful in the diagnostic workup and for clarifying specimen-handling methods. In addition to the red strings and white cores observed in PDAC, mixed red and white strings, gray tissues, and gelatinous tissues are observed. Gray (necrotic) tissues and gelatinous (mucus) tissues are more suitable than histology for cell block or cytological processing. Tumor cells in neuroendocrine tumors (NETs) are numerous in red strings but cannot be observed macroscopically. ROSE might thus be necessary for lesions that may be NETs. Core tissues can be used for genetic tests, such as those used for KRAS mutations and comprehensive genomic profiling. Cytological materials, including slides and LBC specimens, can also be genetic test materials.
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Affiliation(s)
- Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, 710-8602, Japan.
| | - Kaori Nakamura
- Pathological Laboratory, Division of Medical Technology, Kurashiki Central Hospital, Kurashiki, Japan
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Battistella A, Tacelli M, Mapelli P, Schiavo Lena M, Andreasi V, Genova L, Muffatti F, De Cobelli F, Partelli S, Falconi M. Recent developments in the diagnosis of pancreatic neuroendocrine neoplasms. Expert Rev Gastroenterol Hepatol 2024; 18:155-169. [PMID: 38647016 DOI: 10.1080/17474124.2024.2342837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 04/10/2024] [Indexed: 04/25/2024]
Abstract
INTRODUCTION Pancreatic Neuroendocrine Neoplasms (PanNENs) are characterized by a highly heterogeneous clinical and biological behavior, making their diagnosis challenging. PanNENs diagnostic work-up mainly relies on biochemical markers, pathological examination, and imaging evaluation. The latter includes radiological imaging (i.e. computed tomography [CT] and magnetic resonance imaging [MRI]), functional imaging (i.e. 68Gallium [68 Ga]Ga-DOTA-peptide PET/CT and Fluorine-18 fluorodeoxyglucose [18F]FDG PET/CT), and endoscopic ultrasound (EUS) with its associated procedures. AREAS COVERED This review provides a comprehensive assessment of the recent advancements in the PanNENs diagnostic field. PubMed and Embase databases were used for the research, performed from inception to October 2023. EXPERT OPINION A deeper understanding of PanNENs biology, recent technological improvements in imaging modalities, as well as progresses achieved in molecular and cytological assays, are fundamental players for the achievement of early diagnosis and enhanced preoperative characterization of PanNENs. A multimodal diagnostic approach is required for a thorough disease assessment.
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Affiliation(s)
- Anna Battistella
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Matteo Tacelli
- Vita-Salute San Raffaele University, Milan, Italy
- Pancreato-biliary Endoscopy and EUS Division, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Paola Mapelli
- Vita-Salute San Raffaele University, Milan, Italy
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | - Valentina Andreasi
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Luana Genova
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Francesca Muffatti
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Francesco De Cobelli
- Vita-Salute San Raffaele University, Milan, Italy
- Radiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Stefano Partelli
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Massimo Falconi
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
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Conti Bellocchi MC, Bernuzzi M, Brillo A, Bernardoni L, Amodio A, De Pretis N, Frulloni L, Gabbrielli A, Crinò SF. EUS-FNA versus EUS-FNB in Pancreatic Solid Lesions ≤ 15 mm. Diagnostics (Basel) 2024; 14:427. [PMID: 38396466 PMCID: PMC10888305 DOI: 10.3390/diagnostics14040427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 02/08/2024] [Accepted: 02/12/2024] [Indexed: 02/25/2024] Open
Abstract
A small tumor size may impact the diagnostic performance of endoscopic ultrasound-guided tissue acquisition (EUS-TA) for diagnosing solid pancreatic lesions (SPLs). We aimed to compare the diagnostic yield of EUS-guided fine-needle aspiration (FNA) and biopsy (FNB) in SPLs with a diameter ≤ 15 mm. Consecutive patients who underwent EUS-TA for SPLs ≤ 15 mm between January 2015 and December 2022 in a tertiary referral center were retrospectively evaluated. The primary endpoint was diagnostic accuracy. The final diagnosis was based on surgical pathology or disease evolution after a minimum follow-up of 6 months. Inadequate samples were all considered false negatives for the study. Secondary outcomes included sample adequacy, factors impacting accuracy, and safety. We included 368 patients (52.4% male; mean age: 60.2 years) who underwent FNA in 72 cases and FNB in 296. The mean size of SPLs was 11.9 ± 2.6 mm. More than three passes were performed in 5.7% and 61.5% of patients in the FNB and FNA groups, respectively (p < 0.0001). FNB outperformed FNA in terms of diagnostic accuracy (89.8% vs. 79.1%, p = 0.013) and sample adequacy (95.9% vs. 86.1%, p < 0.001). On multivariate analysis, using FNA (OR: 2.10, 95% CI: 1.07-4.48) and a final diagnosis (OR: 3.56, 95% CI: 1.82-6.94) of benign conditions negatively impacted accuracy. Overall, the adverse event rate was 0.8%, including one pancreatitis in the FNA group and one pancreatitis and one bleeding in the FNB group, all mild and conservatively managed. EUS-TA for SPLs ≤ 15 mm has a high diagnostic yield and safety. This study suggests the superiority of FNB over FNA, with better performance even with fewer passes performed.
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Affiliation(s)
- Maria Cristina Conti Bellocchi
- Diagnostic and Interventional Endoscopy of the Pancreas, Pancreas Institute, G.B. Rossi University Hospital, 37134 Verona, Italy; (L.B.); (S.F.C.)
| | - Micol Bernuzzi
- Department of Medicine, Pancreas Institute, G.B. Rossi University Hospital, 37134 Verona, Italy (A.B.); (A.A.); (N.D.P.); (L.F.)
| | - Alessandro Brillo
- Department of Medicine, Pancreas Institute, G.B. Rossi University Hospital, 37134 Verona, Italy (A.B.); (A.A.); (N.D.P.); (L.F.)
| | - Laura Bernardoni
- Diagnostic and Interventional Endoscopy of the Pancreas, Pancreas Institute, G.B. Rossi University Hospital, 37134 Verona, Italy; (L.B.); (S.F.C.)
| | - Antonio Amodio
- Department of Medicine, Pancreas Institute, G.B. Rossi University Hospital, 37134 Verona, Italy (A.B.); (A.A.); (N.D.P.); (L.F.)
| | - Nicolò De Pretis
- Department of Medicine, Pancreas Institute, G.B. Rossi University Hospital, 37134 Verona, Italy (A.B.); (A.A.); (N.D.P.); (L.F.)
| | - Luca Frulloni
- Department of Medicine, Pancreas Institute, G.B. Rossi University Hospital, 37134 Verona, Italy (A.B.); (A.A.); (N.D.P.); (L.F.)
| | - Armando Gabbrielli
- Diagnostic and Interventional Endoscopy of the Pancreas, Pancreas Institute, G.B. Rossi University Hospital, 37134 Verona, Italy; (L.B.); (S.F.C.)
| | - Stefano Francesco Crinò
- Diagnostic and Interventional Endoscopy of the Pancreas, Pancreas Institute, G.B. Rossi University Hospital, 37134 Verona, Italy; (L.B.); (S.F.C.)
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11
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Nakamura K, Notohara K, Nishizaki R, Ishida E, Sato M, Kodera A, Itakura J, Mizuno M. Macroscopic qualitative evaluation of solid pancreatic lesion specimens from endoscopic ultrasound-guided fine needle aspiration/biopsies. Pancreatology 2023; 23:1028-1035. [PMID: 37839924 DOI: 10.1016/j.pan.2023.10.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 08/30/2023] [Accepted: 10/02/2023] [Indexed: 10/17/2023]
Abstract
OBJECTIVES To pathologically clarify the macroscopic features of endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNA/B) specimens in representative pancreatic diseases and establish tissue-handling standards based on the macroscopic findings. METHODS We gathered EUS-FNA/B specimens of cases at our institution with the final diagnoses of pancreatic ductal adenocarcinoma (PDAC, n = 172), neuroendocrine tumor (NET, n = 19), and chronic inflammatory lesion (CIL, n = 24) including autoimmune pancreatitis. We classified the specimens' macroscopic features in five categories (red strings, mixed-red-and-white strings, white cores, gray tissues, gelatinous tissues) and compared the specimens' features on cytological and histological slides. RESULTS All five macroscopic categories were observed in variable combinations in the PDACs; red strings and white cores predominated in the NETs and CILs. White cores represented neoplastic (PDAC, NET) or lesion (CIL) tissues. Mixed-red-and-white strings were unique to PDACs and contained cancerous cells. Neoplastic cells were numerous in red strings in NETs but not the other groups. Gray and gelatinous tissues represented necrosis and mucin, respectively, and the former were almost exclusively observed in PDACs. Red strings, mixed-red-and-white strings, and white cores were suitable for histological examination, whereas gray and gelatinous tissues were suitable for cytological examination. The white cores, mixed-red-and-white strings, and gelatinous tissues may be composed of non-neoplastic tissues such as contaminated gastrointestinal epithelium. In seven PDACs, although white cores were obtained, a histological diagnosis was not established. CONCLUSIONS Macroscopic evaluations of EUS-FNA/B can enable the identification of specimen components and a possible diagnosis. They also contribute to the selection of the optimal tissue-handling methods.
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Affiliation(s)
- Kaori Nakamura
- Pathological Laboratory, Division of Medical Technology, Kurashiki Central Hospital, Kurashiki, Japan
| | - Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Japan.
| | - Ryoji Nishizaki
- Pathological Laboratory, Division of Medical Technology, Kurashiki Central Hospital, Kurashiki, Japan
| | - Etsuji Ishida
- Department of Gastroenterology and Hepatology, Kurashiki Central Hospital, Kurashiki, Japan
| | - Midori Sato
- Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Japan
| | - Akemi Kodera
- Pathological Laboratory, Division of Medical Technology, Kurashiki Central Hospital, Kurashiki, Japan
| | - Junya Itakura
- Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Japan
| | - Motowo Mizuno
- Department of Gastroenterology and Hepatology, Kurashiki Central Hospital, Kurashiki, Japan
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Regolo M, Cardaci N, Salmeri C, Laudani A, Colaci M, Ippolito M, Motta F, Magrì S, Parisi S, Torcitto AG, Malatino L. Pancreatic Neuroendocrine Tumor (Pan-NET) Presented by Abdominal Pain: A Case Report and Literature Review. J Clin Med 2023; 12:6617. [PMID: 37892755 PMCID: PMC10607714 DOI: 10.3390/jcm12206617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 09/24/2023] [Accepted: 10/18/2023] [Indexed: 10/29/2023] Open
Abstract
A pancreatic neuroendocrine tumor (Pan-NET) is a rare neoplasm originating in the neuroendocrine system. Carcinoid syndrome occurs in approximately 19% of patients with functional Pan-NETs, typically when liver metastases occur. In this paper, we describe the case of a patient with a low-grade non-functional Pan-NET, but with a typical clinical presentation of carcinoid syndrome. An 81-year-old male was admitted to our Department of Internal Medicine at Cannizzaro Hospital (Catania, Italy) because of the onset of abdominal pain with nausea, loose stools, and episodic flushing. Firstly, an abdominal contrast-enhanced CT scan showed a small pancreatic hyper-vascular mass; then, a gallium-68 DOTATOC integrated PET/CT revealed an elevated expression of SSTR receptors. Serum chromogranin A and urinary 5-HIAA measurements were negative. We performed an endoscopic ultrasonography (EUS) by a fine-needle biopsy (EUS-FNB), allowing the immunostaining of a small mass (0.8 cm) and the diagnosis of a low-grade (G1) non-functional Pan-NET (NF-Pan-NET). Surgery was waived, while a follow-up strategy was chosen. The early recognition of Pan-NETs, although rare, is necessary to improve the patient's survival. Although helpful to allow for immunostaining, EUS-FNB needs to be warranted in future studies comparing EUS-FNB to EUS-FNA (fine-needle aspiration), which is, to date, reported as the tool of choice to diagnose Pan-NETs.
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Affiliation(s)
- Matteo Regolo
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Nicolas Cardaci
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Clara Salmeri
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Alfredo Laudani
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Michele Colaci
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Massimo Ippolito
- Nuclear Medicine Unit, Cannizzaro Hospital, 95126 Catania, Italy;
| | - Fabio Motta
- Pathological Anatomy Unit, Cannizzaro Hospital, 95126 Catania, Italy;
| | - Salvatore Magrì
- Endoscopy Unit, Cannizzaro Hospital, 95126 Catania, Italy; (S.M.); (S.P.)
| | - Stefanie Parisi
- Endoscopy Unit, Cannizzaro Hospital, 95126 Catania, Italy; (S.M.); (S.P.)
| | | | - Lorenzo Malatino
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
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Pyo JS, Kim NY, Min KW, Oh IH, Lim DH, Son BK. Diagnostic Accuracy of ki-67 Labeling Index in Endoscopic Ultrasonography-Fine-Needle Aspiration Cytology and Biopsy of Pancreatic Neuroendocrine Neoplasms. Diagnostics (Basel) 2023; 13:2756. [PMID: 37685294 PMCID: PMC10487187 DOI: 10.3390/diagnostics13172756] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 08/06/2023] [Accepted: 08/23/2023] [Indexed: 09/10/2023] Open
Abstract
BACKGROUND This study aimed to compare the diagnostic accuracy of the Ki-67 labeling index (LI) between endoscopic ultrasonography-fine-needle aspiration cytology/biopsy (EUS-FNAC/FNB) and surgical specimens of pancreatic neuroendocrine neoplasms (PanNENs). METHODS Conventional meta-analysis and diagnostic test accuracy (DTA) reviews were performed on 17 eligible studies. The DTA review involved calculating the sensitivity, specificity, diagnostic odds ratio (OR), and area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve. In addition, subgroup analysis was conducted based on EUS-FNAC and FNB, tumor grade, and tumor size. RESULTS The overall concordance rate of WHO grade based on Ki-67 LI between the EUS-FNAC/FNB and the surgical specimen was 0.767 (95% confidence interval (CI), 0.713-0.814). Concordance rates of the EUS-FNAC and EUS-FNB subgroups were 0.741 (95% CI, 0.681-0.794) and 0.839 (95% CI, 0.738-0.906), respectively. In the DTA review for grade 3, the sensitivity and specificity were calculated to be 0.786 (95% CI, 0.590-0.917) and 0.998 (95% CI, 0.987-1.000), respectively. The diagnostic OR and AUC of the SROC curve were 150.220 (95% CI, 46.145-489.000) and 0.983, respectively. The sensitivity and specificity were observed to be highest in the grade 1 and 3 subgroups, respectively. CONCLUSIONS Higher concordance of tumor grade based on Ki-67 LI was observed between EUS-FNAC/FNB and surgical specimens, indicating the potential usefulness of Ki-67 LI in predicting PanNEN tumor grade in EUS-FNAC/FNB.
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Affiliation(s)
- Jung-Soo Pyo
- Department of Pathology, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu-si 11759, Gyeonggi-do, Republic of Korea; (J.-S.P.); (K.-W.M.)
| | - Nae Yu Kim
- Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu-si 11759, Gyeonggi-do, Republic of Korea; (N.Y.K.); (I.H.O.); (D.H.L.)
| | - Kyueng-Whan Min
- Department of Pathology, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu-si 11759, Gyeonggi-do, Republic of Korea; (J.-S.P.); (K.-W.M.)
| | - Il Hwan Oh
- Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu-si 11759, Gyeonggi-do, Republic of Korea; (N.Y.K.); (I.H.O.); (D.H.L.)
| | - Dae Hyun Lim
- Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu-si 11759, Gyeonggi-do, Republic of Korea; (N.Y.K.); (I.H.O.); (D.H.L.)
| | - Byoung Kwan Son
- Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu-si 11759, Gyeonggi-do, Republic of Korea; (N.Y.K.); (I.H.O.); (D.H.L.)
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Gopakumar H, Jahagirdar V, Koyi J, Dahiya DS, Goyal H, Sharma NR, Perisetti A. Role of Advanced Gastrointestinal Endoscopy in the Comprehensive Management of Neuroendocrine Neoplasms. Cancers (Basel) 2023; 15:4175. [PMID: 37627203 PMCID: PMC10453187 DOI: 10.3390/cancers15164175] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Revised: 08/15/2023] [Accepted: 08/15/2023] [Indexed: 08/27/2023] Open
Abstract
Neuroendocrine neoplasms (NENs), also called neuroendocrine tumors (NETs), are relatively uncommon, heterogenous tumors primarily originating in the gastrointestinal tract. With the improvement in technology and increasing use of cross-sectional imaging and endoscopy, they are being discovered with increasing frequency. Although traditionally considered indolent tumors with good prognoses, some NENs exhibit aggressive behavior. Timely diagnosis, risk stratification, and management can often be a challenge. In general, small NENs without local invasion or lymphovascular involvement can often be managed using minimally invasive advanced endoscopic techniques, while larger lesions and those with evidence of lymphovascular invasion require surgery, systemic therapy, or a combination thereof. Ideal management requires a comprehensive and accurate understanding of the stage and grade of the tumor. With the recent advancements, a therapeutic advanced endoscopist can play a pivotal role in diagnosing, staging, and managing this rare condition. High-definition white light imaging and digital image enhancing technologies like narrow band imaging (NBI) in the newer endoscopes have improved the diagnostic accuracy of traditional endoscopy. The refinement of endoscopic ultrasound (EUS) over the past decade has revolutionized the role of endoscopy in diagnosing and managing various pathologies, including NENs. In addition to EUS-directed diagnostic biopsies, it also offers the ability to precisely assess the depth of invasion and lymphovascular involvement and thus stage NENs accurately. EUS-directed locoregional ablative therapies are increasingly recognized as highly effective, minimally invasive treatment modalities for NENs, particularly pancreatic NENs. Advanced endoscopic resection techniques like endoscopic submucosal dissection (ESD), endoscopic submucosal resection (EMR), and endoscopic full-thickness resection (EFTR) have been increasingly used over the past decade with excellent results in achieving curative resection of various early-stage gastrointestinal luminal lesions including NENs. In this article, we aim to delineate NENs of the different segments of the gastrointestinal (GI) tract (esophagus, gastric, pancreatic, and small and large intestine) and their management with emphasis on the endoscopic management of these tumors.
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Affiliation(s)
- Harishankar Gopakumar
- Department of Gastroenterology and Hepatology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA;
| | - Vinay Jahagirdar
- Department of Internal Medicine, University of Missouri-Kansas City, Kansas City, MO 64110, USA; (V.J.); (J.K.)
| | - Jagadish Koyi
- Department of Internal Medicine, University of Missouri-Kansas City, Kansas City, MO 64110, USA; (V.J.); (J.K.)
| | - Dushyant Singh Dahiya
- Division of Gastroenterology, Hepatology & Motility, The University of Kansas School of Medicine, Kansas City, KS 66160, USA;
| | - Hemant Goyal
- Department of Surgery, Center for Interventional Gastroenterology at UT (iGUT), The University of Texas Health Science Center, Houston, TX 77054, USA;
| | - Neil R. Sharma
- Advanced Interventional Endoscopy & Endoscopic Oncology (IOSE) Division, GI Oncology Tumor Site Team, Parkview Cancer Institute, 11104 Parkview Circle, Suite 310, Fort Wayne, IN 46845, USA;
| | - Abhilash Perisetti
- Division of Gastroenterology and Hepatology, Kansas City Veteran Affairs, Kansas City, MO 64128, USA
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15
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Nabi Z, Lakhtakia S, Reddy DN. Current status of the role of endoscopy in evaluation and management of gastrointestinal and pancreatic neuroendocrine tumors. Indian J Gastroenterol 2023; 42:158-172. [PMID: 37129761 DOI: 10.1007/s12664-023-01362-8] [Citation(s) in RCA: 2] [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: 03/07/2022] [Accepted: 02/15/2023] [Indexed: 05/03/2023]
Abstract
The incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has increased over the last several decades. In general, NETs are slow-growing neoplasms and the data on the natural history is still evolving. The availability and improved utilization of advanced imaging modalities have allowed the selection of cases suitable for endotherapy. In this regard, endoscopic ultrasound (EUS) has emerged as a central imaging modality to assess the depth of infiltration in gastroduodenal as well as rectal NETs. Enhanced EUS modalities, including contrast-enhanced EUS and EUS elastography, reliably differentiate pancreatic neuroendocrine tumors (PNETs) from adenocarcinomas and may enable prediction of aggressive PNETs. With recent developments in therapeutic endoscopy, a large proportion of GEP-NETs can be safely managed endoscopically. Endoscopic resection techniques, including endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), allow the safe removal of gastroduodenal and rectal NETs. Recent data indicate that modified EMR techniques may be superior to conventional EMR with regard to histologically complete resection. Device-assisted endoscopic full thickness resection is emerging as a safe and effective technique for upper gastrointestinal as well as rectal NETs. In selected cases with PNETs, who are otherwise unfit for surgery, EUS-guided ablation is increasingly being recognized as a safe treatment option. This review focusses on evidence-based approaches to endoscopic evaluation and the management of GEP-NETs with special emphasis on recent advancements.
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Affiliation(s)
- Zaheer Nabi
- Asian Institute of Gastroenterology, Hyderabad, 500 082, India.
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16
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Tacelli M, Bina N, Crinò SF, Facciorusso A, Celsa C, Vanni AS, Fantin A, Antonini F, Falconi M, Monica F, Capurso G, Arcidiacono PG, Barresi L. Reliability of grading preoperative pancreatic neuroendocrine tumors on EUS specimens: a systematic review with meta-analysis of aggregate and individual data. Gastrointest Endosc 2022; 96:898-908.e23. [PMID: 35863518 DOI: 10.1016/j.gie.2022.07.014] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 07/02/2022] [Accepted: 07/08/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Therapy and prognosis of pancreatic neuroendocrine tumors (PanNETs) are strictly related to the Ki-67 index, which defines tumor grading. The criterion standard for the assessment of grading of PanNETs is EUS-guided FNA (EUS-FBAFNA) or EUS-guided fine-needle biopsy sampling (EUS-FNB). Because data on diagnostic accuracy of EUS-FNA and EUS-FNB are heterogeneous, we aimed to analyze the variability in concordance between EUS grading and surgical grading. METHODS The MEDLINE, SCOPUS, and EMBASE databases were searched until November 2021 to identify studies reporting the concordance rate between EUS grading and surgical grading. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled events were calculated using a random-effects model and expressed in terms of pooled prevalence rates. A multivariate meta-regression was performed to find possible sources of heterogeneity. Where available, individual data were analyzed. RESULTS Twenty-six studies with 864 patients undergone EUS-FNA or EUS-FNB and surgical resection for PanNETs were included. The pooled estimate rate for the overall concordance of EUS grading and surgical grading was 80.3% (95% confidence interval, 75.6-85.1). Undergrading (EUS grading < surgical grading) was significantly more frequent with respect to overgrading (14.7% vs 3.5%, P < .001). Individual data analysis showed that among nonconcordant patients, the median Ki-67 difference was 3% (interquartile range, 2-6.15). The type of World Health Organization classification adopted and the median lesion diameter were significantly associated with heterogeneity at meta-regression. CONCLUSIONS EUS is an accurate technique in defining grading in patients with PanNETs, but a margin of error still exists, which should be the focus of future studies to minimize the risk of over- and/or undertreatment.
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Affiliation(s)
- Matteo Tacelli
- Division of Pancreato-Biliary Endoscopy and EUS, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Niccolò Bina
- Division of Pancreato-Biliary Endoscopy and EUS, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy; Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Stefano Francesco Crinò
- Department of Medicine, Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, University Hospital of Verona, Verona, Italy
| | - Antonio Facciorusso
- Department of Medical and Surgical Sciences, Gastroenterology Unit, University of Foggia, Foggia, Italy
| | - Ciro Celsa
- Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Andrea Sbrozzi Vanni
- Gastroenterology and Diagnostic and Operative Digestive Endoscopy, San Camillo Forlanini Hospital, Rome, Italy
| | | | - Filippo Antonini
- Gastroenterology and Digestive Endoscopy Unit, Augusto Murri Hospital, Polytechnic University of Marche, Fermo, Italy
| | - Massimo Falconi
- Vita-Salute San Raffaele University, Milan, Italy; Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy
| | - Fabio Monica
- Gastroenterology and Digestive Endoscopy, "Cattinara" Academic Hospital, Trieste, Italy
| | - Gabriele Capurso
- Division of Pancreato-Biliary Endoscopy and EUS, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy
| | - Paolo Giorgio Arcidiacono
- Division of Pancreato-Biliary Endoscopy and EUS, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Luca Barresi
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
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17
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Iabichino G, Di Leo M, Arena M, Rubis Passoni GG, Morandi E, Turpini F, Viaggi P, Luigiano C, De Luca L. Diagnosis, treatment, and current concepts in the endoscopic management of gastroenteropancreatic neuroendocrine neoplasms. World J Gastroenterol 2022; 28:4943-4958. [PMID: 36160644 PMCID: PMC9494936 DOI: 10.3748/wjg.v28.i34.4943] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 06/29/2022] [Accepted: 08/22/2022] [Indexed: 02/06/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors derived from the neuroendocrine cell system, which that have increased in incidence and prevalence in recent years. Despite improvements in radiological and metabolic imaging, endoscopy still plays a pivotal role in the number of GEP-NENs. Tumor detection, characterization, and staging are essential in management and treatment planning. Upper and lower gastrointestinal (GI) endoscopy is essential for correct localization of the primary tumor site of GI NENs. Endoscopic ultrasonography (EUS) has an important role in the imaging and tissue acquisition of pancreatic NENs and locoregional staging of GI neuroendocrine tumors. Correct staging and histological diagnosis have important prognostic implications. Endoscopic operating techniques allow the removal of small GI NENs in the early stage of mucosal or submucosal invasion of the intestinal wall. Preoperative EUS-guided techniques may help the surgeon locate small and deep tumors, thus avoiding formal pancreatic resections in favor of parenchymal-sparing surgery. Finally, locoregional ablative treatments have been proposed in recent studies with promising results in selected patients.
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Affiliation(s)
| | - Milena Di Leo
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| | - Monica Arena
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| | | | | | - Francesca Turpini
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| | - Paolo Viaggi
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| | - Carmelo Luigiano
- Gastroenterology Section, Grande Ospedale Metropolitano “Bianchi-Melacrino-Morelli”, Reggio Calabria 89124, Italy
| | - Luca De Luca
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
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18
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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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Dietrich CF, Shi L, Koch J, Löwe A, Dong Y, Cui X, Worni M, Jenssen C. Early detection of pancreatic tumors by advanced EUS imaging. Minerva Gastroenterol (Torino) 2022; 68:133-143. [PMID: 33337117 DOI: 10.23736/s2724-5985.20.02789-0] [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] [Indexed: 11/27/2023]
Abstract
The early detection of pancreatic ductal adenocarcinoma (PDAC) dramatically improves outcome. All available state-of-the-art imaging methods allow early detection with EUS being the best technique for exclusion of PDAC and detection of very early PDAC. Etiological differentiation of small SPL is important to guide individually tailored patients' management including radical surgery in resectable PDAC, medical (neoadjuvant or palliative intended) treatment in patients with non-resectable malignancy, pancreatic parenchyma saving strategies in some non-PDAC, and follow-up in particular in low-grade PanNEN or other small benign lesions. Multimodality EUS imaging including B-Mode assessment, elastography, contrast-enhancement and EUS-guided sampling is the most appropriate technique for diagnosis and risk assessment of small SPL. We present a review discussing modern (endoscopic) ultrasound imaging techniques including contrast enhanced ultrasound and elastography for the early detection and characterization of solid pancreatic lesions.
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Affiliation(s)
- Christoph F Dietrich
- Department Allgemeine Innere Medizin, Beau Site Clinic, Salem-Spital, Kliniken Hirslanden, Bern, Switzerland -
| | - Long Shi
- Department of Ultrasound, Jingmen N.2 People's Hospital, Jingmen, China
| | - Jonas Koch
- Department Allgemeine Innere Medizin, Beau Site Clinic, Salem-Spital, Kliniken Hirslanden, Bern, Switzerland
| | - Axel Löwe
- Department Allgemeine Innere Medizin, Beau Site Clinic, Salem-Spital, Kliniken Hirslanden, Bern, Switzerland
| | - Yi Dong
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xinwu Cui
- Department of Medical Ultrasound, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Mathias Worni
- Department of Visceral Surgery, Clarunis, St. Clara Hospital and University Hospital, University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland
- Campus SLB, Swiss Institute for Translational and Entrepreneurial Medicine, Stiftung Lindenhof, Bern, Switzerland
- Department of Surgery, Beau Site Clinic, Bern, Switzerland
| | - Christian Jenssen
- Department of Internal Medicine, Krankenhaus Märkisch Oderland, Strausberg, Germany
- Brandenburg Institute for Clinical Ultrasound, Medical University Brandenburg, Neuruppin, Germany
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Canakis A, Lee LS. Current updates and future directions in diagnosis and management of gastroenteropancreatic neuroendocrine neoplasms. World J Gastrointest Endosc 2022; 14:267-290. [PMID: 35719897 PMCID: PMC9157694 DOI: 10.4253/wjge.v14.i5.267] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 02/14/2022] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms are a heterogenous group of rare neoplasms that are increasingly being discovered, often incidentally, throughout the gastrointestinal tract with varying degrees of activity and malignant potential. Confusing nomenclature has added to the complexity of managing these lesions. The term carcinoid tumor and embryonic classification have been replaced with gastroenteropancreatic neuroendocrine neoplasm, which includes gastrointestinal neuroendocrine and pancreatic neuroendocrine neoplasms. A comprehensive multidisciplinary approach is important for clinicians to diagnose, stage and manage these lesions. While histological diagnosis is the gold standard, recent advancements in endoscopy, conventional imaging, functional imaging, and serum biomarkers complement histology for tailoring specific treatment options. In light of developing technology, our review sets out to characterize diagnostic and therapeutic advancements for managing gastroenteropancreatic neuroendocrine tumors, including innovations in radiolabeled peptide imaging, circulating biomarkers, and endoscopic treatment approaches adapted to different locations throughout the gastrointestinal system.
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Affiliation(s)
- Andrew Canakis
- Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD 21201, United States
| | - Linda S Lee
- Division of Gastroenterology Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States
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21
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Appelstrand A, Bergstedt F, Elf AK, Fagman H, Hedenström P. Endoscopic ultrasound-guided side-fenestrated needle biopsy sampling is sensitive for pancreatic neuroendocrine tumors but inadequate for tumor grading: a prospective study. Sci Rep 2022; 12:5971. [PMID: 35396490 PMCID: PMC8993931 DOI: 10.1038/s41598-022-09923-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 03/30/2022] [Indexed: 11/10/2022] Open
Abstract
Accurate pretreatment grading of pancreatic neuroendocrine tumors (PanNETs) is important to guide patient management. We aimed to evaluate endoscopic ultrasound-guided fine needle biopsy sampling (EUS-FNB) for the preoperative diagnosis and grading of PanNETs. In a tertiary-center setting, patients with suspected PanNETs were prospectively subjected to 22-gauge, reverse-bevel EUS-FNB. The EUS-FNB samples (Ki-67EUS) and corresponding surgical specimens (Ki-67SURG) were analyzed with Ki-67 indexing and thereafter tumor grading, (GRADEEUS) and (GRADESURG) respectively. In total 52 PanNET-patients [median age: 66 years; females: 25/52; surgical resection 22/52 (42%)] were included. EUS-FNB was diagnostic in 44/52 (85%). In 42 available FNB-slides, the median neoplastic cell count was 1034 (IQR: 504-3667) with 32/42 (76%), 22/42 (52%), and 14/42 (33%) cases exceeding 500, 1000, and 2000 neoplastic cells respectively. Ki-67SURG was significantly higher compared to Ki-67EUS with a moderate correlation comparing Ki-67EUS and Ki-67SURG (Pearson r = 0.60, r2 = 0.36, p = 0.011). The GRADEEUS had a weak level of agreement (κ = 0.08) compared with GRADESURG. Only 2/12 (17%) G2-tumors were correctly graded in EUS-FNB-samples. EUS-guided fine needle biopsy sampling is sensitive for preoperative diagnosis of PanNET but biopsy quality is relatively poor. Therefore, the approach seems suboptimal for pretreatment grading of PanNET.
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Affiliation(s)
- Alexander Appelstrand
- Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Fredrik Bergstedt
- Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Anna-Karin Elf
- Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Henrik Fagman
- Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden.,Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Per Hedenström
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. .,Division of Medical Gastroenterology, Department of Internal Medicine, Sahlgrenska University Hospital, Medicinmottagningen, Sahlgrenska Sjukhuset, Blå Stråket 3, 413 35, Gothenburg, Sweden.
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22
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The Utility of Endoscopic-Ultrasonography-Guided Tissue Acquisition for Solid Pancreatic Lesions. Diagnostics (Basel) 2022; 12:diagnostics12030753. [PMID: 35328306 PMCID: PMC8947755 DOI: 10.3390/diagnostics12030753] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 03/13/2022] [Accepted: 03/17/2022] [Indexed: 02/07/2023] Open
Abstract
Endoscopic-ultrasonography-guided tissue acquisition (EUS-TA) has been widely performed for the definitive diagnosis of solid pancreatic lesions (SPLs). As the puncture needles, puncture techniques, and sample processing methods have improved, EUS-TA has shown higher diagnostic yields and safety. Recently, several therapeutic target genomic biomarkers have been clarified in pancreatic ductal carcinoma (PDAC). Although only a small proportion of patients with PDAC can benefit from precision medicine based on gene mutations at present, precision medicine will also be further developed for SPLs as more therapeutic target genomic biomarkers are identified. Advances in next-generation sequencing (NGS) techniques enable the examination of multiple genetic mutations in limited tissue samples. EUS-TA is also useful for NGS and will play a more important role in determining treatment strategies. In this review, we describe the utility of EUS-TA for SPLs.
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23
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Notohara K, Kamisawa T, Furukawa T, Fukushima N, Uehara T, Kasashima S, Iwasaki E, Kanno A, Kawashima A, Kubota K, Kuraishi Y, Motoya M, Naitoh I, Nishino T, Sakagami J, Shimizu K, Tomono T, Aishima S, Fukumura Y, Hirabayashi K, Kojima M, Mitsuhashi T, Naito Y, Ohike N, Tajiri T, Yamaguchi H, Fujiwara H, Ibuki E, Kobayashi S, Miyaoka M, Nagase M, Nakashima J, Nakayama M, Oda S, Taniyama D, Tsuyama S, Watanabe S, Ikeura T, Kawa S, Okazaki K. Concordance of the histological diagnosis of type 1 autoimmune pancreatitis and its distinction from pancreatic ductal adenocarcinoma with endoscopic ultrasound-guided fine needle biopsy specimens: an interobserver agreement study. Virchows Arch 2022; 480:565-575. [PMID: 34820715 DOI: 10.1007/s00428-021-03236-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2021] [Revised: 09/25/2021] [Accepted: 11/07/2021] [Indexed: 10/28/2022]
Abstract
The histological diagnosis of type 1 autoimmune pancreatitis (AIP) based on the findings obtained by an endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is feasible, but the diagnostic consistency of this method has not been confirmed. We determined the interobserver agreement among 20 pathologists regarding the diagnosis of type 1 AIP, including the distinction from pancreatic ductal adenocarcinoma (PDAC) using large tissue samples obtained by EUS-FNB. After guidance for diagnosing AIP with biopsy tissues was provided, a round 2 was performed. The median sensitivity and specificity for diagnosing PDAC vs. non-neoplastic diseases were 95.2% and 100%, respectively. In groups of specialists (n = 7) and the generalists (n = 13), Fleiss' к-values increased from 0.886 to 0.958 and from 0.750 to 0.816 in round 2. The concordance was fair or moderate for obliterative phlebitis and storiform fibrosis but slight for ductal lesion of type 1 AIP. Discordant results were due to ambiguous findings and biopsy tissue limitations. Among the specialists, the ratio of cases with perfect agreement regarding the presence of storiform fibrosis increased in round 2, but agreement regarding obliterative phlebitis or ductal lesions was not improved. Although the histological definite diagnosis of type 1 AIP was achieved by most observers in > 60% of the cases, the confidence levels varied. Because some ambiguities exist, the histological diagnostic levels based on the diagnostic criteria of type 1 AIP should not be taken for granted. Guidance is effective for improving accurate PDAC diagnoses (notably by recognizing acinar-ductal metaplasia) and for evaluating storiform fibrosis.
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Affiliation(s)
- Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, 710-8602, Japan.
| | - Terumi Kamisawa
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Toru Furukawa
- Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | | | - Takeshi Uehara
- Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan
| | - Satomi Kasashima
- Department of Clinical Laboratory Science, Graduate School of Health Science, Kanazawa University, Kanazawa, Japan
| | - Eisuke Iwasaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Atsushi Kanno
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke, Japan
| | - Atsuhiro Kawashima
- Department of Diagnostic Pathology, National Hospital Organization Kanazawa Medical Center, Kanazawa, Japan
| | - Kensuke Kubota
- Depatment of Endoscopy, Yokohama City University Hospital, Yokohama, Japan
| | - Yasuhiro Kuraishi
- Department of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Masayo Motoya
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Itaru Naitoh
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takayoshi Nishino
- Department of Gastroenterology, Tokyo Women's Medical University, Yachiyo Medical Center, Yachiyo, Japan
| | - Junichi Sakagami
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Fukuchiyama City Hospital, Fukuchiyama, Japan
| | - Kyoko Shimizu
- Department of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Teruko Tomono
- Department of Gastroenterology, Kyoto University Hospital, Kyoto, Japan
| | - Shinichi Aishima
- Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga, Japan
| | - Yuki Fukumura
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Kenichi Hirabayashi
- Department of Pathology, Tokai University School of Medicine, Isehara, Japan
| | - Motohiro Kojima
- Division of Pathology, Research Center for Innovative Oncology, National Cancer Center, Kashiwa, Japan
| | - Tomoko Mitsuhashi
- Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan
| | - Yoshiki Naito
- Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan
| | - Nobuyuki Ohike
- Department of Pathology, Showa University Fujigaoka Hospital, Yokohama, Japan
- Division of Pathology, Shizuoka Cancer Center, Sunto-gun, Japan
| | - Takuma Tajiri
- Department of Diagnostic Pathology, Tokai University Hachioji Hospital, Hachioji, Japan
| | | | - Hideyo Fujiwara
- Department of Pathology, Kawasaki Medical School, Kurashiki, Japan
| | - Emi Ibuki
- Department of Diagnostic Pathology, Kagawa University, Kita-gun, Japan
| | - Shota Kobayashi
- Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan
| | - Masashi Miyaoka
- Department of Pathology, Tokai University School of Medicine, Isehara, Japan
| | - Mamiko Nagase
- Department of Organ Pathology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Junko Nakashima
- Department of Pathology, Kochi Medical School, Kochi University, Nangoku, Japan
| | - Masamichi Nakayama
- Department of Pathology, Kurume University School of Medicine, Kurume, Japan
| | - Shinsuke Oda
- Department of Diagnostic Pathology, Tottori Prefectural Central Hospital, Tottori, Japan
| | - Daiki Taniyama
- Molecular Pathology, Hiroshima University, Hiroshima, Japan
| | - Sho Tsuyama
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | | | - Tsukasa Ikeura
- Department of Gastroenterology and Hepatology, Kansai Medical University, Hirakata, Japan
| | - Shigeyuki Kawa
- Department of Internal Medicine, Matsumoto Dental University, Shiojiri, Japan
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24
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Gan Q, Roy-Chowdhuri S, Duose DY, Stewart JM, Coronel E, Bhutani MS, Lee JH, Weston B, Ge PS, Ross WA, Maitra A. Adequacy evaluation and use of pancreatic adenocarcinoma specimens for next-generation sequencing acquired by endoscopic ultrasound-guided FNA and FNB. Cancer Cytopathol 2021; 130:275-283. [PMID: 34905283 DOI: 10.1002/cncy.22533] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 09/01/2021] [Accepted: 10/06/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Endoscopic ultrasound-guided tissue acquisition (EUS-TA), especially endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), is the mainstay of tissue acquisition for the diagnosis of pancreatic ductal adenocarcinoma (PDAC). Recently, endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using flexible biopsy needles has been used for patients with PDAC in an effort to increase diagnostic yields and biomarker testing. However, the role of EUS-TA in biomarker testing for personalized therapy or precise chemotherapy for PDAC is not well established. METHODS PDAC cases with specimens acquired through concurrent EUS-FNA and EUS-FNB were identified retrospectively. Smears were prepared from EUS-FNA sampling, and cell blocks (CBs) were prepared from EUS-FNB sampling. Rapid onsite evaluation was conducted for all cases for diagnostic adequacy. The adequacy for biomarker testing, including next-generation sequencing (NGS) and immunohistochemistry (IHC) assays, was evaluated, and cases with smears and CBs adequate for NGS were processed for targeted NGS. RESULTS There were 26 PDAC cases concurrently sampled by EUS-FNA and EUS-FNB. EUS-FNA smears for all 26 cases and EUS-FNB CBs for 20 cases (77%) were diagnostic for PDAC. Twenty-one smears (81%) and 11 CBs (42%) were adequate for NGS. Nine cases with both smears and CBs adequate for NGS underwent NGS, which identified clinically significant gene mutation variants, including KRAS, TP53, and SMAD4 mutations. CONCLUSIONS Both EUS-FNA and EUS-FNB can provide optimal material for targeted NGS for PDACs. In PDAC cases subjected to concurrent EUS-FNA and EUS-FNB, EUS-FNA specimens had greater diagnostic yields and more adequate material for NGS than EUS-FNB specimens, whereas EUS-FNB was more suitable for IHC-based biomarker testing.
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Affiliation(s)
- Qiong Gan
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Sinchita Roy-Chowdhuri
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Dzifa Yawa Duose
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - John M Stewart
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Emmanuel Coronel
- Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Manoop S Bhutani
- Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jeffrey H Lee
- Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Brian Weston
- Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Phillip S Ge
- Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - William A Ross
- Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Anirban Maitra
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
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25
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Tacelli M, Petrone MC, Capurso G, Muffatti F, Andreasi V, Partelli S, Doglioni C, Falconi M, Arcidiacono PG. Diagnostic accuracy of EUS-FNA in the evaluation of pancreatic neuroendocrine neoplasms grading: Possible clinical impact of misclassification. Endosc Ultrasound 2021; 10:372-380. [PMID: 34677159 PMCID: PMC8544016 DOI: 10.4103/eus-d-20-00261] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 07/12/2021] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Prognosis of pancreatic neuroendocrine neoplasms (PanNENs) mostly depend on tumor stage and grade, determined by Ki-67 labeling index. EUS-FNA is considered the gold-standard technique to obtain it. The aims of our study were to establish diagnostic accuracy of preoperative EUS-FNA Ki-67 evaluation considering final pathological assessment on surgical specimen as gold standard and to investigate the possible impact on prognosis of misclassification. METHODS This is a retrospective study from a prospectively collected database. EUS-FNA grading (eG) and surgical one (sG) measured according to Ki-67 proliferative index values, according to 2017 WHO classification, were compared. eG-sG correlation was evaluated by Spearman index. Logistic regression investigated factors associated with misclassification. Prognostic difference in terms of progression-free survival was evaluated by Kaplan Meier method. RESULTS One hundred and twelve PanNENs patients enrolled. In 13.4% of patients (15/112) EUS-FNA "undergraded" patients (eG1 vs. sG2), while in 12.5% (n = 14) it "overgraded" PanNENs (eG2 to sG1). No misclassifications in G3 patients. In patients with tumors <20 mm (n = 44), 2 (4.5%) eG1 and 10 (22.7%) eG2 were finally classified respectively as G2 and G1 at surgical histology. No factors, as i.e. the lesions' size or their morphological aspect, were associated with misclassification. In overgraded PanNENs, no progression occurred, while in patients correctly classified/undergraded the progression rate was 14.3%. CONCLUSIONS This is the largest cohort of surgical PanNENs with preoperative EUS-FNA grading evaluation. Despite an acceptable eG-sG correlation, about 25% of patients are misclassified. Clinical impact of misclassification should be carefully considered especially in small tumors undergoing observation.
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Affiliation(s)
- Matteo Tacelli
- Division of Pancreato-Biliary Endoscopy and EUS, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milano, Italy
| | - Maria Chiara Petrone
- Division of Pancreato-Biliary Endoscopy and EUS, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milano, Italy
| | - Gabriele Capurso
- Division of Pancreato-Biliary Endoscopy and EUS, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milano, Italy
| | - Francesca Muffatti
- Division of Pancreato-Biliary Endoscopy and EUS, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milano, Italy
| | - Valentina Andreasi
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milano, Italy
| | - Stefano Partelli
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milano, Italy
| | - Claudio Doglioni
- Department of Pathology, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milano, Italy
| | - Massimo Falconi
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milano, Italy
| | - Paolo Giorgio Arcidiacono
- Division of Pancreato-Biliary Endoscopy and EUS, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milano, Italy
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26
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Automatic Segmentation of Pancreatic Tumors Using Deep Learning on a Video Image of Contrast-Enhanced Endoscopic Ultrasound. J Clin Med 2021; 10:jcm10163589. [PMID: 34441883 PMCID: PMC8397137 DOI: 10.3390/jcm10163589] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 08/10/2021] [Accepted: 08/12/2021] [Indexed: 02/06/2023] Open
Abstract
Background: Contrast-enhanced endoscopic ultrasound (CE-EUS) is useful for the differentiation of pancreatic tumors. Using deep learning for the segmentation and classification of pancreatic tumors might further improve the diagnostic capability of CE-EUS. Aims: The aim of this study was to evaluate the capability of deep learning for the automatic segmentation of pancreatic tumors on CE-EUS video images and possible factors affecting the automatic segmentation. Methods: This retrospective study included 100 patients who underwent CE-EUS for pancreatic tumors. The CE-EUS video images were converted from the originals to 90-s segments with six frames per second. Manual segmentation of pancreatic tumors from B-mode images was performed as ground truth. Automatic segmentation was performed using U-Net with 100 epochs and was evaluated with 4-fold cross-validation. The degree of respiratory movement (RM) and tumor boundary (TB) were divided into 3-degree intervals in each patient and evaluated as possible factors affecting the segmentation. The concordance rate was calculated using the intersection over union (IoU). Results: The median IoU of all cases was 0.77. The median IoUs in TB-1 (clear around), TB-2, and TB-3 (unclear more than half) were 0.80, 0.76, and 0.69, respectively. The IoU for TB-1 was significantly higher than that of TB-3 (p < 0.01). However, there was no significant difference between the degrees of RM. Conclusions: Automatic segmentation of pancreatic tumors using U-Net on CE-EUS video images showed a decent concordance rate. The concordance rate was lowered by an unclear TB but was not affected by RM.
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27
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Imaoka H, Sasaki M, Hashimoto Y, Watanabe K, Miyazawa S, Shibuki T, Mitsunaga S, Ikeda M. Impact of Endoscopic Ultrasound-Guided Tissue Acquisition on Decision-Making in Precision Medicine for Pancreatic Cancer: Beyond Diagnosis. Diagnostics (Basel) 2021; 11:1195. [PMID: 34209310 PMCID: PMC8307595 DOI: 10.3390/diagnostics11071195] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 06/21/2021] [Accepted: 06/22/2021] [Indexed: 02/07/2023] Open
Abstract
Precision medicine in cancer treatment refers to targeted therapy based on the evaluation of biomarkers. Although precision medicine for pancreatic cancer (PC) remains challenging, novel biomarker-based therapies, such as pembrolizumab, olaparib, and entrectinib, have been emerging. Most commonly, endoscopic ultrasound-guided tissue acquisition (EUS-TA) had been used for the diagnosis of PC until now. However, advances in EUS-TA devices and biomarker testing, especially next-generation sequencing, have opened up the possibility of sequencing of various genes even in limited amounts of tissue samples obtained by EUS-TA, and identifying potential genetic alterations as therapeutic targets. Precision medicine benefits only a small population of patients with PC, but biomarker-based therapy has shown promising results in patients who once had no treatment options. Now, the role of EUS-TA has extended beyond diagnosis into decision-making regarding the treatment of PC. In this review, we mainly discuss tissue sampling by EUS-TA for biomarker testing and the current status of precision medicine for PC.
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Affiliation(s)
- Hiroshi Imaoka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa 277-8577, Chiba, Japan; (M.S.); (Y.H.); (K.W.); (S.M.); (T.S.); (S.M.); (M.I.)
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28
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Melita G, Pallio S, Tortora A, Crinò SF, Macrì A, Dionigi G. Diagnostic and Interventional Role of Endoscopic Ultrasonography for the Management of Pancreatic Neuroendocrine Neoplasms. J Clin Med 2021; 10:2638. [PMID: 34203922 PMCID: PMC8232656 DOI: 10.3390/jcm10122638] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 05/28/2021] [Accepted: 06/07/2021] [Indexed: 12/11/2022] Open
Abstract
Pancreatic neuroendocrine neoplasms (PanNENs) are relatively rare, but their incidence has increased significantly in the last decades. Precise diagnosis and prognostic stratification are crucial for proper patient management. Endoscopic ultrasound (EUS) is the modality of choice for diagnosis of solid pancreatic tumors, showing a higher tumor detection rate than other imaging modalities, especially for small size lesions. EUS also serves as a guide for preoperative sampling and other interventions. EUS-tissue acquisition is a safe and highly accurate technique for cyto/histological diagnosis of PanNENs with a well-demonstrated correlation between Ki-67 proliferation index values and tumor grading on EUS and surgical specimens according to the WHO 2017 classification. Furthermore, the possibility of a preoperative EUS-guided fine needle tattooing or fiducial markers placement may help the surgeon to locate small and deep tumors, thus avoiding formal pancreatic resections in favor of parenchymal-sparing surgery. Finally, locoregional ablative treatments using either ethanol injection or radiofrequency ablation have been proposed in recent studies with promising results in order to control symptoms or reduce tumor burden in selected patients unfit for surgery with functioning or non-functioning PanNENs. This article review highlights the current role of EUS in PanNENs management, focusing on the present and future applications of EUS-guided interventions.
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Affiliation(s)
- Giuseppinella Melita
- Department of Human Pathology of Adult and Pediatric Age, University of Messina, 98100 Messina, Italy; (A.M.); (G.D.)
| | - Socrate Pallio
- Department of Internal Medicine and Medical Therapy, University of Messina, 98100 Messina, Italy;
| | - Andrea Tortora
- Digestive Endoscopy Unit, Azienda Ospedaliera Universitaria Policlinico, G. Martino, 98100 Messina, Italy;
| | | | - Antonio Macrì
- Department of Human Pathology of Adult and Pediatric Age, University of Messina, 98100 Messina, Italy; (A.M.); (G.D.)
| | - Gianlorenzo Dionigi
- Department of Human Pathology of Adult and Pediatric Age, University of Messina, 98100 Messina, Italy; (A.M.); (G.D.)
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29
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Del Vecchio Blanco G, Palmieri G, Giannarelli D, Formica V, Portarena I, Nardecchia A, Troncone E, Benassi M, Giudice E, Anselmo A, Tisone G, Roselli M, Monteleone G, Paoluzi OA. Factors influencing diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in pancreatic and biliary tumors. Scand J Gastroenterol 2021; 56:498-504. [PMID: 33539716 DOI: 10.1080/00365521.2021.1880628] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [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 Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is influenced by several factors, primarily operator expertise. Formal training in EUS-FNA, as suggested by the European Society of Gastrointestinal Endoscopy and the American Society for Gastrointestinal Endoscopy guidelines, is not always available and is often expensive and time-consuming. In this study we evaluate factors influencing the diagnostic accuracy of pancreatic EUS-FNA. METHODS In a retrospective study, 557 consecutive EUS-FNAs were evaluated. Several variables relating to the procedures were considered to calculate the EUS-FNA performance over eight years. RESULTS A total of 308 out of 557 EUS-FNAs were selected. Overall sensitivity of EUS-FNA was 66% (95% CI: 60.8-71.8), specificity 100%, and diagnostic accuracy 69% (95% CI: 64.0-74.4). An increase in diagnostic accuracy was observed to >90% using a new fine-needle biopsy (FNB) needle and in the case of simultaneous sampling of primary and metastatic lesions. Diagnostic accuracy >80% was observed after 250 procedures, in the absence of rapid on-site cytopathological examination (ROSE). Multivariate logistic regression analysis confirmed that the FNB needle, operator skill, and double EUS-FNA sampling are associated with high diagnostic accuracy. CONCLUSIONS The learning curve for EUS-FNA may be longer and a considerable number of procedures are needed to achieve high diagnostic accuracy in the absence of ROSE. However, the use of FNB needles and the simultaneous sampling of primary and metastatic lesions can rapidly improve the diagnostic accuracy of the procedure.
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Affiliation(s)
| | - Giampiero Palmieri
- Anatomic Pathology Unit, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
| | - Diana Giannarelli
- Biostatistical Unit, Regina Elena Institute-Hospital Physiotherapy Institutes, Rome, Italy
| | | | | | | | - Edoardo Troncone
- Gastroenterology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Michela Benassi
- Radiotherapy Unit, Department of Oncohematology, University of Rome Tor Vergata, Rome, Italy
| | - Emilia Giudice
- Radiotherapy Unit, Department of Oncohematology, University of Rome Tor Vergata, Rome, Italy
| | - Alessandro Anselmo
- Transplant Surgery Unit, Department of Surgery, University of Rome Tor Vergata, Rome, Italy
| | - Giuseppe Tisone
- Transplant Surgery Unit, Department of Surgery, University of Rome Tor Vergata, Rome, Italy
| | - Mario Roselli
- Oncology Unit, University of Rome Tor Vergata, Rome, Italy
| | - Giovanni Monteleone
- Gastroenterology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Omero Alessandro Paoluzi
- Gastroenterology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
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Crinò SF, Ammendola S, Meneghetti A, Bernardoni L, Conti Bellocchi MC, Gabbrielli A, Landoni L, Paiella S, Pin F, Parisi A, Mastrosimini MG, Amodio A, Frulloni L, Facciorusso A, Larghi A, Manfrin E. Comparison between EUS-guided fine-needle aspiration cytology and EUS-guided fine-needle biopsy histology for the evaluation of pancreatic neuroendocrine tumors. Pancreatology 2021; 21:443-450. [PMID: 33390343 DOI: 10.1016/j.pan.2020.12.015] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 12/09/2020] [Accepted: 12/21/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES Studies comparing EUS-guided fine-needle aspiration (EUS-FNA) with EUS-guided fine-needle biopsy (EUS-FNB) for the evaluation of pancreatic neuroendocrine tumors (pNETs) are lacking. We aimed at comparing EUS-FNA with EUS-FNB in terms of Ki-67 proliferative index (PI) estimation capability, cellularity of the samples, and reliability of Ki-67 PI/tumor grading compared with surgical specimens. METHODS Patients diagnosed with pNETs on EUS and/or surgical specimens were retrospectively identified. Specimens were re-evaluated to assess Ki-67 PI feasibility, sample cellularity by manual counting, and determination of Ki-67 PI value. Outcomes in the EUS-FNA and EUS-FNB groups were compared. Kendall rank test was used for Ki-67 PI correlation between EUS and surgical specimens. Subgroup analysis including small (≤20 mm), non-functioning pNETs was performed. RESULTS Three-hundred samples from 292 lesions were evaluated: 69 EUS-FNA cytology and 231 EUS-FNB histology. Ki-67 PI feasibility was similar for EUS-FNA and EUS-FNB (91.3% vs. 95.7%, p = 0.15), while EUS-FNB performed significantly better in the subgroup of 179 small pNETs (88.2% vs. 96.1%, p = 0.04). Rate of poor cellulated (<500 cells) specimens was equal between EUS-FNA and EUS-FNB. A significant correlation for Ki-67 PI values between EUS and 92 correspondent surgical specimens was found in both groups, but it was stronger with EUS-FNB (tau = 0.626, p < 0.0001 vs. tau = 0.452, p = 0.031). Correct grading estimation was comparable between the two groups (p = 0.482). CONCLUSION Our study showed stronger correlation for Ki-67 values between EUS-FNB and surgical specimens, and that EUS-FNB outperformed EUS-FNA in the evaluation of small pNETs. EUS-FNB should become standard of care for grading assessment of suspected pNETs.
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Affiliation(s)
- Stefano Francesco Crinò
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy.
| | - Serena Ammendola
- Department of Diagnostics and Public Health, G.B. Rossi University Hospital, Verona, Italy
| | - Anna Meneghetti
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | - Laura Bernardoni
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | | | - Armando Gabbrielli
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | - Luca Landoni
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Salvatore Paiella
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Federico Pin
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | - Alice Parisi
- Department of Diagnostics and Public Health, G.B. Rossi University Hospital, Verona, Italy
| | | | - Antonio Amodio
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | - Luca Frulloni
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | - Antonio Facciorusso
- Digestive Endoscopy Unit, Department of Medical Sciences, University of Foggia, Foggia, Italy
| | - Alberto Larghi
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Erminia Manfrin
- Department of Diagnostics and Public Health, G.B. Rossi University Hospital, Verona, Italy
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Ishii T, Katanuma A, Toyonaga H, Chikugo K, Nasuno H, Kin T, Hayashi T, Takahashi K. Role of Endoscopic Ultrasound in the Diagnosis of Pancreatic Neuroendocrine Neoplasms. Diagnostics (Basel) 2021; 11:diagnostics11020316. [PMID: 33672085 PMCID: PMC7919683 DOI: 10.3390/diagnostics11020316] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Accepted: 02/10/2021] [Indexed: 12/16/2022] Open
Abstract
Although pancreatic neuroendocrine neoplasms (PNENs) are relatively rare tumors, their number is increasing with advances in diagnostic imaging modalities. Even small lesions that are difficult to detect using computed tomography or magnetic resonance imaging can now be detected with endoscopic ultrasound (EUS). Contrast-enhanced EUS is useful, and not only diagnosis but also malignancy detection has become possible by evaluating the vascularity of tumors. Pathological diagnosis using EUS with fine-needle aspiration (EUS-FNA) is useful when diagnostic imaging is difficult. EUS-FNA can also be used to evaluate the grade of malignancy. Pooling the data of the studies that compared the PNENs grading between EUS-FNA samples and surgical specimens showed a concordance rate of 77.5% (κ-statistic = 0.65, 95% confidence interval = 0.59–0.71, p < 0.01). Stratified analysis for small tumor size (2 cm) showed that the concordance rate was 84.5% and the kappa correlation index was 0.59 (95% confidence interval = 0.43–0.74, p < 0.01). The evolution of ultrasound imaging technologies such as contrast-enhanced and elastography and the artificial intelligence that analyzes them, the evolution of needles, and genetic analysis, will further develop the diagnosis and treatment of PNENs in the future.
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Affiliation(s)
- Tatsuya Ishii
- Correspondence: ; Tel.: +81-11-681-8111; Fax: +81-11-685-2967
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Paiella S, Landoni L, Rota R, Valenti M, Elio G, Crinò SF, Manfrin E, Parisi A, Cingarlini S, D'Onofrio M, Scarpa A, Lawlor RT, Bernardoni L, Capelli P, Nessi C, Miotto M, Gabbrielli A, Bassi C, Salvia R. Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis and grading of pancreatic neuroendocrine tumors: a retrospective analysis of 110 cases. Endoscopy 2020; 52:988-994. [PMID: 32498099 DOI: 10.1055/a-1180-8614] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Data on the reliability of the Ki-67 index and grading calculations from endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic neuroendocrine tumors (PanNETs) are controversial. We aimed to assess the accuracy of these data compared with histology. METHODS Cytological analysis from EUS-FNA in patients with suspected PanNETs (n = 110) were compared with resection samples at a single institution. A minimum of 2000 cells were considered to be adequate for grading. Correlation and agreement between cytology and histology in grading and Ki-67 values, respectively, were investigated. Secondary outcomes included the diagnostic performance of EUS-FNA. RESULTS EUS-FNA samples were adequate for PanNET diagnosis and PanNET grading in 98/110 (89.1 %) and 77/110 (70.0 %) patients, respectively; thus, 77 samples were adequate for comparing cytology vs. histology. There were 67 (62.0 %), 40 (36.4 %), and 1 (0.9 %) patients with a final diagnosis of G1, G2, and G3 tumors, respectively. EUS-FNA grading was concordant with surgical pathology in 81.8 % of patients; under- and overgrading occurred in 15.6 % and 2.6 %, respectively. The overall level of agreement for grading was moderate (Cohen's κ = 0.59, 95 % confidence interval [CI] 0.34 - 0.78). Spearman's rho for Ki-67 in tumors ≤ 20 mm and > 20 mm was strong and moderate, respectively (rho = 0.68, 95 %CI 0.47 - 0.83; rho = 0.59, 95 %CI 0.35 - 0.75). The Bland - Altman plot showed that the Ki-67 values were comparable and reproducible between the two measurements. CONCLUSIONS Although they were not available for a significant number of patients, grading and Ki-67 values from cytology correlated with histology moderately to strongly.
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Affiliation(s)
- Salvatore Paiella
- General and Pancreatic Surgery Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Luca Landoni
- General and Pancreatic Surgery Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Roberta Rota
- General and Pancreatic Surgery Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Matteo Valenti
- General and Pancreatic Surgery Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Giovanni Elio
- General and Pancreatic Surgery Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Stefano Francesco Crinò
- Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Erminia Manfrin
- Department of Diagnostics and Public Health, Section of Pathology, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Alice Parisi
- Department of Diagnostics and Public Health, Section of Pathology, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Sara Cingarlini
- Oncology Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Mirko D'Onofrio
- Radiology Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Section of Pathology, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
- ARC-Net Applied Research Center, University and Hospital Trust of Verona, Verona, Italy
| | - Rita Teresa Lawlor
- ARC-Net Applied Research Center, University and Hospital Trust of Verona, Verona, Italy
| | - Laura Bernardoni
- Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Paola Capelli
- Department of Diagnostics and Public Health, Section of Pathology, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Chiara Nessi
- General and Pancreatic Surgery Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Marco Miotto
- General and Pancreatic Surgery Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Armando Gabbrielli
- Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Claudio Bassi
- General and Pancreatic Surgery Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Roberto Salvia
- General and Pancreatic Surgery Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
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EUS-guided fine needle tattooing (EUS-FNT) for preoperative localization of small pancreatic neuroendocrine tumors (p-NETs): a single-center experience. Surg Endosc 2020; 35:486-492. [PMID: 32959183 DOI: 10.1007/s00464-020-07996-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Accepted: 09/14/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND and study aims Pancreatic neuroendocrine tumors (pNETs) can be difficult to detect intra-operatively. The aim of this paper is to evaluate the safety and efficacy of preoperative endoscopic ultrasound guided fine needle tattooing (EUS-FNT) to facilitate intra-operative detection of pNETs. PATIENTS AND METHODS Sixteen patients with pNETs (8 insulinoma and 8 non-functional pancreatic neuroendocrine tumors) underwent EUS-FNT. The procedure was carried out using the conventional curvilinear EUS. Tattooing was performed by intralesional injection of 1-2 mL of Spot® ink (Spot®, GI Supply, Comp Hill, PA, US) using a standard 22 gauge EUS-FNA needle. RESULTS All identified pNETs could be tattooed in one session. The procedure was well tolerated in all patients without any complication. The time interval between tattooing and surgery was between 1 and 565 days (mean of 52 days). Nine patients underwent open and seven laparoscopic surgery. The tattooed lesions could be recognized in all but one patient. In one patient, a small hematoma secondary to the EUS-FNT was observed. Pathological examination of the resection specimen showed local R0 resection in all cases, and no interference with the specimen evaluation was encountered. CONCLUSIONS Our results suggest that EUS-guided FNT is a safe and useful method to mark preoperatively small (≤ 2 cm) pNETs.
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David Y, Kim MK. Is Endoscopic Ultrasound-Fine Needle Aspiration for Ki67 Aspirational Enough? Clin Endosc 2020; 53:111-113. [PMID: 32156105 PMCID: PMC7137562 DOI: 10.5946/ce.2020.045] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 02/20/2020] [Indexed: 12/21/2022] Open
Affiliation(s)
- Yakira David
- Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Michelle Kang Kim
- Samuel Bronfman Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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