|
1
|
Itonaga M, Ashida R, Kitano M. Updated techniques and evidence for endoscopic ultrasound-guided tissue acquisition from solid pancreatic lesions. DEN OPEN 2025; 5:e399. [PMID: 38911353 PMCID: PMC11190023 DOI: 10.1002/deo2.399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Accepted: 06/03/2024] [Indexed: 06/25/2024]
Abstract
Endoscopic ultrasound-guided tissue acquisition (EUS-TA), including fine-needle aspiration (EUS-FNA) and fine-needle biopsy (EUS-FNB), has revolutionized specimen collection from intra-abdominal organs, especially the pancreas. Advances in personalized medicine and more precise treatment have increased demands to collect specimens with higher cell counts, while preserving tissue structure, leading to the development of EUS-FNB needles. EUS-FNB has generally replaced EUS-FNA as the procedure of choice for EUS-TA of pancreatic cancer. Various techniques have been tested for their ability to enhance the diagnostic performance of EUS-TA, including multiple methods of sampling at the time of puncture, on-site specimen evaluation, and specimen processing. In addition, advances in next-generation sequencing have made comprehensive genomic profiling of EUS-TA samples feasible in routine clinical practice. The present review describes updates in EUS-TA sampling techniques of pancreatic lesions, as well as methods for their evaluation.
Collapse
Affiliation(s)
- Masahiro Itonaga
- Second Department of Internal MedicineWakayama Medical UniversityWakayamaJapan
| | - Reiko Ashida
- Second Department of Internal MedicineWakayama Medical UniversityWakayamaJapan
| | - Masayuki Kitano
- Second Department of Internal MedicineWakayama Medical UniversityWakayamaJapan
| |
Collapse
|
|
2
|
Ko SW, Jo IH, Yoon SB. Feasibility and clinical utility of endoscopic ultrasound-guided tissue acquisition for comprehensive genomic profiling in pancreatic cancer: A systematic review and meta-analysis. Pancreatology 2025; 25:89-97. [PMID: 39732591 DOI: 10.1016/j.pan.2024.12.012] [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: 06/20/2024] [Revised: 11/09/2024] [Accepted: 12/21/2024] [Indexed: 12/30/2024]
Abstract
BACKGROUND Endoscopic ultrasound-guided tissue acquisition (EUS-TA) has become essential for diagnosing pancreatic ductal adenocarcinoma (PDAC) and is increasingly utilized for comprehensive genome profiling (CGP) to advance precision medicine. This systematic review and meta-analysis assess the feasibility and clinical utility of EUS-TA samples for CGP in PDAC. METHODS We conducted a thorough systematic literature search in PubMed, EMBASE, and the Cochrane Library up to October 2023. Key outcomes included sequencing success rates, detection rates of four major driver genes and actionable genes, and concordance rates with other sample types or methodologies. RESULTS A total of 23 studies met the inclusion criteria. The pooled sequencing success rate was 83.9 % [95 % confidence interval (CI): 75.8-89.7 %]. No significant difference was observed in sequencing success rates between fine needle aspiration and biopsy (odds ratio 1.77, 95 % CI 0.70-4.47). Meta-regression analysis revealed that the minimum DNA requirement for CGP significantly influenced sequencing success rates. The pooled mutation rate for K-ras was 86.4 % (95 % CI 83.6-88.8), while potentially actionable mutations had a pooled rate of 17.7 % (95 % CI 12.8-23.8). The concordance rate between CGP results from EUS-guided samples and surgical specimens was 81.6 % (95 % CI 68.2-90.1). CONCLUSION Comprehensive genomic profiling of PDAC using EUS-TA-derived samples demonstrated feasibility in clinical settings. Approximately 18 % of patients undergoing CGP exhibited potentially actionable mutations, highlighting the potential for personalized therapeutic approaches.
Collapse
Affiliation(s)
- Sung Woo Ko
- Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Ik Hyun Jo
- Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, South Korea
| | - Seung Bae Yoon
- Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
| |
Collapse
|
|
3
|
Chung KH, Lee SH. Optimal tissue acquisition method for pancreatic mass. Dig Endosc 2024. [PMID: 39722220 DOI: 10.1111/den.14976] [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: 07/06/2024] [Accepted: 11/20/2024] [Indexed: 12/28/2024]
Abstract
Pancreatic masses pose a diagnostic difficulty due to the technical complexities related to tissue acquisition. Endoscopic ultrasound (EUS)-guided tissue acquisition has transformed the field by allowing access to pancreatic lesions through fine-needle and biopsy. However, diagnostic accuracy differs based on tumor characteristics and procedural factors. This narrative review explores the nuances of tissue acquisition methods for pancreatic tumors, including factors such as tumor location, size, histological characteristics, and needle selection. It assesses the efficacy of different needle designs and maneuvers, including suction techniques and needle passes. Moreover, the diverse tissue preparation methods, including cytological smear, cell block, and direct histology, are discussed, highlighting the importance of tailored approaches based on tumor characteristics. Additionally, the roles of macroscopic on-site evaluation and rapid on-site evaluation in optimizing specimen adequacy are investigated. Furthermore, percutaneous ultrasound-guided biopsy is considered an alternative approach, particularly in settings where EUS is impractical. Additionally, the review emphasizes the emerging trend of using tissue for genetic testing and molecular analysis, requiring high-quality sample acquisition. Future directions in tissue acquisition techniques and their integration into clinical practice are discussed, providing promising avenues for pancreatic disease diagnosis and treatment.
Collapse
Affiliation(s)
- Kwang Hyun Chung
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University Hospital Seoul, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Sang Hyub Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| |
Collapse
|
|
4
|
Dhar J, Samanta J, Nabi Z, Aggarwal M, Conti Bellocchi MC, Facciorusso A, Frulloni L, Crinò SF. Endoscopic Ultrasound-Guided Pancreatic Tissue Sampling: Lesion Assessment, Needles, and Techniques. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:2021. [PMID: 39768901 PMCID: PMC11727853 DOI: 10.3390/medicina60122021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 11/15/2024] [Accepted: 12/03/2024] [Indexed: 01/12/2025]
Abstract
Endoscopic ultrasound (EUS)-guided tissue sampling includes the techniques of fine needle aspiration (FNA) and fine needle biopsy (FNB), and both procedures have revolutionized specimen collection from the gastrointestinal tract, especially from remote/inaccessible organs. EUS-FNB has replaced FNA as the procedure of choice for tissue acquisition in solid pancreatic lesions (SPLs) across various society guidelines. FNB specimens provide a larger histological tissue core (preserving tissue architecture) with fewer needle passes, and this is extremely relevant in today's era of precision and personalized molecular medicine. Innovations in needle tip design are constantly under development to maximize diagnostic accuracy by enhancing histological sampling capabilities. But, apart from the basic framework of the needle, various other factors play a role that influence diagnostic outcomes, namely, sampling techniques (fanning, aspiration or suction, and number of passes), collection methods, on-site evaluation (rapid, macroscopic, or visual), and specimen processing. The choice taken depends strongly on the endoscopist's preference, available resources at the disposal, and procedure objectives. Hence, in this review, we explicate in detail the concepts and available literature at our disposal on the topic of EUS-guided pancreatic tissue sampling to best guide any practicing gastroenterologist/endoscopist in a not-to-ideal set-up, which EUS-guided tissue acquisition technique is the "best" for their case to augment their diagnostic outcomes.
Collapse
Affiliation(s)
- Jahnvi Dhar
- Department of Gastroenterology, Adesh Medical College and Hospital, Kurukshetra 136134, India;
| | - Jayanta Samanta
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India;
| | - Zaheer Nabi
- Department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad 500082, India;
| | - Manik Aggarwal
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
| | - Maria Cristina Conti Bellocchi
- Department of Medicine, Diagnostic and Interventional Endoscopy of the Pancreas, The Pancreas Institute, University Hospital of Verona, 37134 Verona, Italy; (M.C.C.B.); (L.F.)
| | - Antonio Facciorusso
- Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy;
- Clinical Effectiveness Research Group, Faculty of Medicine, Institute of Health and Society, University of Oslo, 0372 Oslo, Norway
| | - Luca Frulloni
- Department of Medicine, Diagnostic and Interventional Endoscopy of the Pancreas, The Pancreas Institute, University Hospital of Verona, 37134 Verona, Italy; (M.C.C.B.); (L.F.)
| | - Stefano Francesco Crinò
- Department of Medicine, Diagnostic and Interventional Endoscopy of the Pancreas, The Pancreas Institute, University Hospital of Verona, 37134 Verona, Italy; (M.C.C.B.); (L.F.)
| |
Collapse
|
|
5
|
Yang JL, Zhang JF, Gu JY, Gao M, Zheng MY, Guo SX, Zhang T. Strategic insights into the cultivation of pancreatic cancer organoids from endoscopic ultrasonography-guided biopsy tissue. World J Gastroenterol 2024; 30:4532-4543. [PMID: 39563744 PMCID: PMC11572629 DOI: 10.3748/wjg.v30.i42.4532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 09/10/2024] [Accepted: 10/16/2024] [Indexed: 10/31/2024] Open
Abstract
BACKGROUND The frequent suboptimal efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) to culture pancreatic cancer (PC) organoids (PCOs) poses a major challenge in the advancement of personalized medicine for advanced PC. AIM To explore how to obtain appropriate puncture tissues from EUS-FNB and optimize the strategy for efficiently constructing PCOs, providing an efficient tool for the advancement of personalized medicine. METHODS Patients who underwent EUS-FNB for the diagnosis of PC tissue were prospectively enrolled. We refined the endoscopic biopsy procedures and organoid cultivation techniques. All tissue specimens verified by on-site pathological assessment were cultured in a semi-suspended medium in a microfluidic environment. We assessed differences in PCOs cultured beyond and below five generations examining patient demographics, specimen and organoid attributes, and the sensitivity of organoids to a panel of clinical drugs through cell viability assays. RESULTS In this study, 16 patients with PC were recruited, one sample was excluded because onsite cytopathology showed no tumor cells. Successful organoid generation occurred in 93.3% (14 of 15) of the EUS-FNB specimens, with 60% (9 of 15) sustaining over five generations. Among these patients, those with a history of diabetes, familial cancer, or larger tumors exhibited enhanced PCO expandability. The key factors influencing long-term PCOs expansion included initial needle sample quality (P = 0.005), rapid initiation of organoid culture post-isolation (P ≤ 0.001), and high organoid activity (P = 0.031). Drug sensitivity analysis revealed a partial response in two patients following therapeutic intervention and surgery and stable disease in four patients, indicating a moderate correlation between organoid response and clinical outcomes. CONCLUSION Optimal initial needle sampling, rapid and precise biopsy sample processing, process isolated samples as soon as possible, and sufficient cellular material are crucial for successful cultivating PCOs. High organoid activity is an important factor in maintaining their long-term expansion, which is essential for shortening the time of drug sensitivity analysis and is the basis of PC research.
Collapse
Affiliation(s)
- Jia-Li Yang
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China
| | - Jun-Feng Zhang
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China
| | - Jian-You Gu
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China
| | - Mei Gao
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China
| | - Ming-You Zheng
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China
| | - Shi-Xiang Guo
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China
| | - Tao Zhang
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China
| |
Collapse
|
|
6
|
Lee TS, Lee SH, Kim J, Lee MH, Cho IR, Ryu JK, Kim YT, Paik WH. Increased needle passes for comparable diagnostic yield in endoscopic ultrasound-guided tissue acquisition for pancreatic stiff lesions measured by elastography. Pancreatology 2024; 24:1192-1198. [PMID: 39277479 DOI: 10.1016/j.pan.2024.09.011] [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: 04/02/2024] [Revised: 07/15/2024] [Accepted: 09/10/2024] [Indexed: 09/17/2024]
Abstract
BACKGROUND/OBJECTIVES Pancreatic cancer is characterized by tissue stiffness due to the high concentration of cancer-associated fibroblasts and extracellular matrix. Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is performed to diagnose pancreatic cancer but yields false-negative results attributed to inadequate specimens. EUS-elastography is a real-time assessment method to pancreatic tissue stiffness. This study aims to investigate the correlation between diagnostic yield and the number of needle passes based on the stiffness measured by elastography. METHODS Patients who underwent EUS-TA for pancreatic solid mass were retrospectively reviewed and included in this study. The number of needle passes during EUS-TA was determined based on macroscopic on-site evaluation. Tissue stiffness measurements were taken using EUS-elastography. The primary study outcome was the diagnostic yield. The secondary outcome included the number of needle passes required for a diagnosis. RESULTS A total of 652 patients were included. The average stiffness differed depending on the location of the tumor, and high-stiffness group had more malignant lesions. Although the diagnostic yield was not significantly different between groups, the number of needle passes was significantly higher in the high-stiffness group (3.6 ± 1.0 vs. 3.2 ± 0.9, p < 0.001). CONCLUSIONS The higher the stiffness of the pancreatic mass in EUS-elastography, the more needle passes are required to achieve a comparable diagnostic yield.
Collapse
Affiliation(s)
- Tae Seung Lee
- Department of Internal Medicine, Seoul National University Hospital, 101, Daehak-ro, Jongno-Gu, Seoul, Republic of Korea
| | - Sang Hyub Lee
- Department of Internal Medicine, Seoul National University Hospital, 101, Daehak-ro, Jongno-Gu, Seoul, Republic of Korea
| | - Junyeol Kim
- Department of Internal Medicine, Seoul National University Hospital, 101, Daehak-ro, Jongno-Gu, Seoul, Republic of Korea
| | - Myeong Hwan Lee
- Department of Internal Medicine, Seoul National University Hospital, 101, Daehak-ro, Jongno-Gu, Seoul, Republic of Korea
| | - In Rae Cho
- Department of Internal Medicine, Seoul National University Hospital, 101, Daehak-ro, Jongno-Gu, Seoul, Republic of Korea
| | - Ji Kon Ryu
- Department of Internal Medicine, Seoul National University Hospital, 101, Daehak-ro, Jongno-Gu, Seoul, Republic of Korea
| | - Yong-Tae Kim
- Department of Internal Medicine, Seoul National University Hospital, 101, Daehak-ro, Jongno-Gu, Seoul, Republic of Korea
| | - Woo Hyun Paik
- Department of Internal Medicine, Seoul National University Hospital, 101, Daehak-ro, Jongno-Gu, Seoul, Republic of Korea.
| |
Collapse
|
|
7
|
O’Connor CA, Harrold E, Lin D, Walch H, Gazzo A, Ranganathan M, Kane S, Keane F, Schoenfeld J, Moss D, Thurtle-Schmidt DM, Suehnholz SP, Chakravarty D, Balogun F, Varghese A, Yu K, Kelsen D, Latham A, Weigelt B, Park W, Stadler Z, O’Reilly EM. Lynch Syndrome and Somatic Mismatch Repair Variants in Pancreas Cancer. JAMA Oncol 2024; 10:1511-1518. [PMID: 39235819 PMCID: PMC11378065 DOI: 10.1001/jamaoncol.2024.3651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Accepted: 05/20/2024] [Indexed: 09/06/2024]
Abstract
Importance Microsatellite (MS) instability (MSI-H) occurs frequently in Lynch syndrome (LS)-associated tumors and is associated with response to immune checkpoint blockade (ICB) therapy. MSI-H is conferred by germline or somatic variants in mismatch repair genes. The contribution of somatic oncogenesis to MSI-H in pancreatic cancer (PC) is unknown. Objective To evaluate an LS-related PC cohort to define clinicogenomic features, describe somatic MSI-H cases (germline negative), characterize response to ICB, and guide preferred MS testing methods. Design, Setting, and Participants This single-institution, retrospective analysis was conducted from March 2012 to July 2023 at Memorial Sloan Kettering Cancer Center and included 55 patients with PC and either an LS germline pathogenic variant (gPV) or somatic mismatch repair (MMR) variant. Main Outcomes and Measures Composite MMR and MS status determined using orthogonal methods. An artificial intelligence classifier was used to account for low-cellularity specimens. Demographic and clinical data were abstracted from medical record. Zygosity status and somatic comutation landscape analyzed. Results Fifty-five patients (23 women [42%]) had PC and an MMR variant: 32 (58%) had LS (LS cohort) and 23 (42%) had a somatic MMR variant (no germline pathogenic variant, somatic MMR cohort). In the LS cohort, 10 (31%) had gMSH2, 9 (28%) gMSH6, 8 (25%) gPMS2, 4 (13%) gMLH1, 1 (3%) gEPCAM. The median age at diagnosis was 68 years (range, 45-88 years). For composite MS status, 17 (59%) were MSI-H, 12 (41%) MS stable, and 3 MS unknown. Five cases were reclassified as MSI-H by the artificial intelligence classifier. In the somatic MMR cohort, 11 (48%) had MSH6, 7 (30%) MLH1, 3 (13%) MSH2, and 2 (9%) PMS2. The median age at diagnosis was 72 years (range, 66-85 years). For composite MS status, 10 (43%) were MSI-H, 11 (48%) MS stable, and 2 (9%) MS indeterminate. Six cases were reclassified as MSI-H by the artificial intelligence classifier. For the LS and somatic MMR cohorts, 20 received ICB (n = 17 MSI-H). The median ICB duration was 27.7 months (95% CI, 11.5 to not reached); the disease control rate was 80%. Conclusion The results of this cross-sectional study suggest that MSI-H occurs due to LS or somatic oncogenesis in PC. Orthogonal MS testing is key in PC; the artificial intelligence classifier reclassified approximately 20% of cases, most of which were low cellularity. ICB for patients with LS or somatic MSI-H PC provided significant benefit.
Collapse
Affiliation(s)
- Catherine A. O’Connor
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
- Department of Biology, Davidson College, Davidson, North Carolina
| | - Emily Harrold
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
- Mater Misericordiae University Hospital Dublin, Dublin, Ireland
| | - David Lin
- Kravis Center for Molecular Oncology, Memorial Sloan Kettering, New York, New York
| | - Henry Walch
- Kravis Center for Molecular Oncology, Memorial Sloan Kettering, New York, New York
| | - Andrea Gazzo
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Megha Ranganathan
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Sarah Kane
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Fergus Keane
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Joshua Schoenfeld
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Drew Moss
- Mount Sinai Morningside West, New York, New York
| | | | - Sarah P. Suehnholz
- Human Oncology Pathogenesis Program, Sloan Kettering Institute, New York, New York
| | - Debyani Chakravarty
- Human Oncology Pathogenesis Program, Sloan Kettering Institute, New York, New York
| | - Fiyinfolu Balogun
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
- David M. Rubenstein Center for Pancreas Cancer Research, New York, New York
- Department of Medicine, Weill Cornell Medical College, New York, New York
| | - Anna Varghese
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
- David M. Rubenstein Center for Pancreas Cancer Research, New York, New York
- Department of Medicine, Weill Cornell Medical College, New York, New York
| | - Kenneth Yu
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
- David M. Rubenstein Center for Pancreas Cancer Research, New York, New York
- Department of Medicine, Weill Cornell Medical College, New York, New York
| | - David Kelsen
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
- David M. Rubenstein Center for Pancreas Cancer Research, New York, New York
- Department of Medicine, Weill Cornell Medical College, New York, New York
| | - Alicia Latham
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
- David M. Rubenstein Center for Pancreas Cancer Research, New York, New York
| | - Britta Weigelt
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
- Department of Medicine, Weill Cornell Medical College, New York, New York
| | - Wungki Park
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
- David M. Rubenstein Center for Pancreas Cancer Research, New York, New York
- Department of Medicine, Weill Cornell Medical College, New York, New York
| | - Zsofia Stadler
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
- Department of Medicine, Weill Cornell Medical College, New York, New York
| | - Eileen M. O’Reilly
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
- David M. Rubenstein Center for Pancreas Cancer Research, New York, New York
- Department of Medicine, Weill Cornell Medical College, New York, New York
| |
Collapse
|
|
8
|
Machicado JD, Sheth SG, Chalhoub JM, Forbes N, Desai M, Ngamruengphong S, Papachristou GI, Sahai V, Nassour I, Abidi W, Alipour O, Amateau SK, Coelho-Prabhu N, Cosgrove N, Elhanafi SE, Fujii-Lau LL, Kohli DR, Marya NB, Pawa S, Ruan W, Thiruvengadam NR, Thosani NC, Qumseya BJ. American Society for Gastrointestinal Endoscopy guideline on role of endoscopy in the diagnosis and management of solid pancreatic masses: methodology and review of evidence. Gastrointest Endosc 2024; 100:e1-e78. [PMID: 39269378 DOI: 10.1016/j.gie.2024.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 06/02/2024] [Indexed: 09/15/2024]
Affiliation(s)
- Jorge D Machicado
- Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA
| | - Sunil G Sheth
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Jean M Chalhoub
- Division of Gastroenterology and Hepatology, Staten Island University Hospital, Northwell Health, Staten Island, New York, USA
| | - Nauzer Forbes
- Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Madhav Desai
- Center for Interventional Gastroenterology at UTHealth, McGovern Medical School, Houston, Texas, USA
| | - Saowanee Ngamruengphong
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Georgios I Papachristou
- Division of Gastroenterology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Vaibhav Sahai
- Division of Hematology and Oncology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Ibrahim Nassour
- Division of Surgical Oncology, University of Florida, Gainesville, Florida, USA
| | - Wasif Abidi
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA
| | - Omeed Alipour
- Division of Gastroenterology, University of Washington Medical Center, Seattle, Washington, USA
| | - Stuart K Amateau
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota Medical Center, Minneapolis, Minnesota, USA
| | | | - Natalie Cosgrove
- Center for Interventional Endoscopy, AdventHealth, Orlando, Florida, USA
| | - Sherif E Elhanafi
- Division of Gastroenterology, Texas Tech University Health Sciences Center, El Paso, Texas, USA
| | | | - Divyanshoo R Kohli
- Pancreas and Liver Clinic, Providence Sacred Medical Center, Elon Floyd School of Medicine, Washington State University, Spokane, Washington, USA
| | - Neil B Marya
- Division of Gastroenterology, UMass Chan Medical School, Worcester, Massachusetts, USA
| | - Swati Pawa
- Department of Gastroenterology, Wake Forest School of Medicine, Winston Salem, North Carolina, USA
| | - Wenly Ruan
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - Nikhil R Thiruvengadam
- Division of Gastroenterology and Hepatology, Loma Linda University, Loma Linda, California, USA
| | - Nirav C Thosani
- Center for Interventional Gastroenterology at UTHealth, McGovern Medical School, Houston, Texas, USA
| | - Bashar J Qumseya
- Department of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida, USA
| |
Collapse
|
|
9
|
Pan Y, Ran T, Zhang X, Qin X, Zhang Y, Zhou C, Zou D. Adequacy of EUS-guided fine-needle aspiration and fine-needle biopsy for next-generation sequencing in pancreatic malignancies: A systematic review and meta-analysis. Endosc Ultrasound 2024; 13:366-375. [PMID: 39802109 PMCID: PMC11723693 DOI: 10.1097/eus.0000000000000097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2025] Open
Abstract
Background and Objectives A majority of pancreatic malignancies are unresectable at the time of presentation and require EUS-guided fine-needle aspiration or fine-needle biopsy (EUS-FNA/FNB) for diagnosis. With the advent of precision therapy, there is an increasing need to use EUS-FNA/FNB sample for genetic analysis. Next-generation sequencing (NGS) is a preferred technology to detect genetic mutations with high sensitivity in small specimens. We performed a meta-analysis to evaluate the adequacy of EUS-FNA/FNB for NGS in pancreatic malignancies. Methods PubMed, Embase, Cochrane Library, and Web of Science were searched from database inception to November 11, 2023. The primary outcome was the proportion of sufficient sample acquired by EUS-FNA/FNB in pancreatic malignancies for NGS. Secondary outcomes were the proportion of sufficient sample for NGS in pancreatic ductal adenocarcinoma (PDAC) and the detection rates of mutations in KRAS, TP53, CDKN2A, and SMAD4 and actionable mutations in PDAC. The pooled proportions were calculated using a random-effects model. Potential sources of heterogeneity were investigated with subgroup analyses and meta-regression. Results Twenty studies with 881 samples were included. The pooled adequacy of EUS-FNA/FNB sample for NGS was 89.9% (95% CI, 80.8%-96.7%) in pancreatic malignancies and 92.0% (95% CI, 81.3%-98.8%) in PDAC. Screening sample suitability before NGS testing was associated with lower adequacy in subgroup analysis (79.7% vs. 98.4%, P = 0.001). The pooled prevalences of mutations in KRAS, TP53, CDKN2A, and SMAD4 in PDAC were 87.4% (95% CI, 83.2%-91.2%), 62.6% (95% CI, 53.2%-71.7%), 20.6% (95% CI, 11.9%-30.8%), and 19.4% (95% CI, 11.2%-29.1%), respectively. The pooled prevalence of potentially actionable mutations in PDAC was 14.5% (95% CI, 8.2%-22.0%). Conclusions In the majority of cases, EUS-FNA/FNB can acquire adequate sample for NGS and identify tumor-specific mutations in patients with pancreatic malignancies. Strict pre-analysis screening criteria may negatively impact the sample adequacy and the success rate for NGS.
Collapse
Affiliation(s)
| | | | | | | | | | - Chunhua Zhou
- Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China
| | - Duowu Zou
- Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China
| |
Collapse
|
|
10
|
Tiong J, Nguyen P, Sritharan M, Lundy J, Shen H, Kumar B, Swan M, Jenkins B, Croagh D. Evaluation of Needles in Endoscopic Ultrasound-Guided Tissue Acquisition of Pancreatic Cancer for Genetic Yield and Quality. Cureus 2024; 16:e68431. [PMID: 39360054 PMCID: PMC11445693 DOI: 10.7759/cureus.68431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/01/2024] [Indexed: 10/04/2024] Open
Abstract
BACKGROUND Endoscopic ultrasound-guided fine needle biopsy (FNB) is the gold standard in tissue acquisition of pancreatic ductal adenocarcinoma (PDAC). There is a paucity of evidence of the impact of needle type or size on the genetic yield and quality. METHODS Patients 18 years and older with PDAC who underwent FNB were retrospectively identified from a single database from 2016 to 2021. Genetic quantity is measured in micrograms (µg) and quality defined by RNA or DNA integrity number (RIN and DIN). FNB needles examined were Acquire 22 gauge (Boston Scientific, Marlborough, MA, USA) and ProCore 22 and 20 gauges (Cook Medical, Bloomington, IN, USA). RESULTS Two hundred seventy-seven patients were identified. ProCore 20G needle procured higher RNA quantity (4125.8µg, IQR: 2003.8, 5954.8, p = 0.012) compared to ProCore 22G (2050µg IQR: 966.4, 3181.6) and Acquire 22G (2310.6µg, IQR: 1439.3, 4312). Median DNA quantity was 3340.5µg (Acquire 22G), 2610.4µg (ProCore 22G) and 3499.7µg (ProCore 20G) (p = 0.763). Median DIN was 7.3 (Acquire 22G and ProCore 22G) and 7.4 (ProCore 20G) (p = 0.449). Median RIN was 3.0 (Acquire 22G and ProCore 22G) and 2.7 (ProCore 20G) (p = 0.886). CONCLUSION ProCore 20G was associated with higher quantity of RNA. There were no differences in the quality acquired by different needles.
Collapse
Affiliation(s)
| | - Phi Nguyen
- Department of Surgery, Monash Health, Melbourne, AUS
| | | | - Joanne Lundy
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Melbourne, AUS
| | - Henry Shen
- Department of Surgery, Monash Health, Melbourne, AUS
| | - Beena Kumar
- Department of Anatomical Pathology, Monash Health, Melbourne, AUS
| | - Michael Swan
- Department of Gastroenterology, Monash Health, Melbourne, AUS
| | - Brendan Jenkins
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Melbourne, AUS
| | - Daniel Croagh
- Department of Surgery, Monash Health, Melbourne, AUS
| |
Collapse
|
|
11
|
Takeshita K, Hijioka S, Nagashio Y, Hara H, Agarie D, Kawasaki Y, Takasaki T, Yagi S, Hagiwara Y, Okamoto K, Yamashige D, Fukuda S, Kuwada M, Komori Y, Okada M, Maruki Y, Morizane C, Ueno H, Yatabe Y, Okusaka T. Study Protocol for a Prospective Self-Controlled Trial on Success in Meeting Comprehensive Genomic Profiling Analysis Criteria for Specimens Obtained by Endoscopic Ultrasound-Guided Tissue Acquisition Using a 19G Needle from Primary and Metastatic Lesions in Pancreatic Cancer with Metastatic Lesions: The PRIMATE Study. Diseases 2024; 12:182. [PMID: 39195181 DOI: 10.3390/diseases12080182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 08/01/2024] [Accepted: 08/09/2024] [Indexed: 08/29/2024] Open
Abstract
EUS-TA in unresectable pancreatic cancer requires not only a tissue diagnosis but also tissue collection in anticipation of comprehensive genomic profiling. However, the optimal puncture target remains controversial. Therefore, the Primary and Metastatic Lesions in Pancreatic Cancer (PRIMATE) study was designed to clarify the optimal target by comparing the success rates for meeting OncoGuide NCC Oncopanel (NOP) analysis criteria on pre-check primary and metastatic lesion specimens obtained during the same EUS-TA session in patients with invasive pancreatic ductal adenocarcinoma. In this ongoing prospective study, two specimens, each from primary and metastatic lesions, are obtained by EUS-TA (typically using a 19G fine-needle biopsy needle) in patients with invasive pancreatic ductal adenocarcinoma. The primary endpoint is the proportion of EUS-TA specimens that meet NOP analysis criteria during pre-check (i.e., tumor cellularity of ≥20% and a tissue area of ≥4 mm2), which are then compared between primary and metastatic lesions. This study has been approved by the National Cancer Center Institutional Review Board (Research No. 2022-168). The results of this study will be reported at an international conference and published in an international peer-reviewed journal. The trial registration number is UMIN 000048966.
Collapse
Affiliation(s)
- Kotaro Takeshita
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
- Department of Gastroenterology, Tane General Hospital, Osaka 550-0025, Japan
| | - Susumu Hijioka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Yoshikuni Nagashio
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Hidenobu Hara
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Daiki Agarie
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Yuki Kawasaki
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Tetsuro Takasaki
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Shin Yagi
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Yuya Hagiwara
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Kohei Okamoto
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Daiki Yamashige
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Soma Fukuda
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Masaru Kuwada
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Yasuhiro Komori
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Mao Okada
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Yuta Maruki
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Chigusa Morizane
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Hideki Ueno
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Yasushi Yatabe
- Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Takuji Okusaka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| |
Collapse
|
|
12
|
Fukuda S, Hijioka S, Nagashio Y, Yamashige D, Agarie D, Hagiwara Y, Okamoto K, Yagi S, Komori Y, Kuwada M, Maruki Y, Morizane C, Ueno H, Hiraoka N, Tsuchiya K, Okusaka T. Utility of Transpapillary Biopsy and Endoscopic Ultrasound-Guided Tissue Acquisition for Comprehensive Genome Profiling of Unresectable Biliary Tract Cancer. Cancers (Basel) 2024; 16:2819. [PMID: 39199592 PMCID: PMC11353131 DOI: 10.3390/cancers16162819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Revised: 08/04/2024] [Accepted: 08/09/2024] [Indexed: 09/01/2024] Open
Abstract
Tissue sampling in biliary tract cancer (BTC) is generally performed through transpapillary biopsy (TPB) or endoscopic ultrasound-guided tissue acquisition (EUS-TA). For the first time, we compared the suitability of specimens obtained using TPB and EUS-TA to determine the optimal tissue-sampling method for comprehensive genome profiling (CGP) analysis in patients with unresectable BTC (UR-BTC). Pathology precheck criteria for CGP analysis comprised the OncoGuide NCC Oncopanel System (NCCOP) and FoundationOne CDx (F1CDx). Seventy-eight patients with UR-BTC (35 TPB and 43 EUS-TA) were included. The NCCOP analysis suitability achievement rate was higher in EUS-TA specimens than in TPB specimens (34.9% vs. 8.6%, p = 0.007), whereas that of F1CDx was 0% in both groups. EUS-TA was identified as an independent factor that contributed to the suitability of the NCCOP analysis. The suitability of the NCCOP analysis of EUS-TA specimens showed a tendency to be higher for mass lesions (43.8% vs. 9.1%, p = 0.065), especially for target size ≥ 18.5 mm, and lower for perihilar cholangiocarcinoma (0% vs. 41.7%, p = 0.077). In TPB, papillary-type lesions (66.7% vs. 3.2%, p = 0.016) and peroral cholangioscopy-assisted biopsies (50.0% vs. 3.3%, p = 0.029) showed better potential for successful NCCOP analysis. EUS-TA is suitable for NCCOP analysis in UR-BTC and may be partially complemented by TPB.
Collapse
Affiliation(s)
- Soma Fukuda
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; (S.F.); (Y.N.); (D.Y.); (D.A.); (Y.H.); (K.O.); (S.Y.); (Y.K.); (M.K.); (Y.M.); (C.M.); (H.U.); (T.O.)
- Department of Gastroenterology, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan;
| | - Susumu Hijioka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; (S.F.); (Y.N.); (D.Y.); (D.A.); (Y.H.); (K.O.); (S.Y.); (Y.K.); (M.K.); (Y.M.); (C.M.); (H.U.); (T.O.)
| | - Yoshikuni Nagashio
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; (S.F.); (Y.N.); (D.Y.); (D.A.); (Y.H.); (K.O.); (S.Y.); (Y.K.); (M.K.); (Y.M.); (C.M.); (H.U.); (T.O.)
| | - Daiki Yamashige
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; (S.F.); (Y.N.); (D.Y.); (D.A.); (Y.H.); (K.O.); (S.Y.); (Y.K.); (M.K.); (Y.M.); (C.M.); (H.U.); (T.O.)
| | - Daiki Agarie
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; (S.F.); (Y.N.); (D.Y.); (D.A.); (Y.H.); (K.O.); (S.Y.); (Y.K.); (M.K.); (Y.M.); (C.M.); (H.U.); (T.O.)
| | - Yuya Hagiwara
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; (S.F.); (Y.N.); (D.Y.); (D.A.); (Y.H.); (K.O.); (S.Y.); (Y.K.); (M.K.); (Y.M.); (C.M.); (H.U.); (T.O.)
- Department of Gastroenterology, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan;
| | - Kohei Okamoto
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; (S.F.); (Y.N.); (D.Y.); (D.A.); (Y.H.); (K.O.); (S.Y.); (Y.K.); (M.K.); (Y.M.); (C.M.); (H.U.); (T.O.)
| | - Shin Yagi
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; (S.F.); (Y.N.); (D.Y.); (D.A.); (Y.H.); (K.O.); (S.Y.); (Y.K.); (M.K.); (Y.M.); (C.M.); (H.U.); (T.O.)
| | - Yasuhiro Komori
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; (S.F.); (Y.N.); (D.Y.); (D.A.); (Y.H.); (K.O.); (S.Y.); (Y.K.); (M.K.); (Y.M.); (C.M.); (H.U.); (T.O.)
| | - Masaru Kuwada
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; (S.F.); (Y.N.); (D.Y.); (D.A.); (Y.H.); (K.O.); (S.Y.); (Y.K.); (M.K.); (Y.M.); (C.M.); (H.U.); (T.O.)
| | - Yuta Maruki
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; (S.F.); (Y.N.); (D.Y.); (D.A.); (Y.H.); (K.O.); (S.Y.); (Y.K.); (M.K.); (Y.M.); (C.M.); (H.U.); (T.O.)
| | - Chigusa Morizane
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; (S.F.); (Y.N.); (D.Y.); (D.A.); (Y.H.); (K.O.); (S.Y.); (Y.K.); (M.K.); (Y.M.); (C.M.); (H.U.); (T.O.)
| | - Hideki Ueno
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; (S.F.); (Y.N.); (D.Y.); (D.A.); (Y.H.); (K.O.); (S.Y.); (Y.K.); (M.K.); (Y.M.); (C.M.); (H.U.); (T.O.)
| | - Nobuyoshi Hiraoka
- Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan;
| | - Kiichiro Tsuchiya
- Department of Gastroenterology, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan;
| | - Takuji Okusaka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; (S.F.); (Y.N.); (D.Y.); (D.A.); (Y.H.); (K.O.); (S.Y.); (Y.K.); (M.K.); (Y.M.); (C.M.); (H.U.); (T.O.)
| |
Collapse
|
|
13
|
Maruo M, Ikeura T, Takaori A, Ikeda M, Nakamaru K, Ito T, Masuda M, Mitsuyama T, Nakayama S, Shimatani M, Takaoka M, Shibata N, Boku S, Yasuda T, Miyazaki H, Matsumura K, Yamaki S, Hashimoto D, Satoi S, Naganuma M. Impact of endoscopic ultrasound-guided tissue acquisition on prognosis and peritoneal lavage cytology in resectable or borderline resectable pancreatic ductal adenocarcinoma. Pancreatology 2024; 24:787-795. [PMID: 38871559 DOI: 10.1016/j.pan.2024.06.001] [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: 12/25/2023] [Revised: 05/20/2024] [Accepted: 06/02/2024] [Indexed: 06/15/2024]
Abstract
OBJECTIVES This study aimed to evaluate the clinical impact of preoperative endoscopic ultrasound-guided tissue acquisition (EUS-TA) on the prognosis and incidence of positive peritoneal lavage cytology (PLC) during laparotomy or staging laparoscopy in patients with resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC). METHODS We retrospectively collected data from patients diagnosed with body and tail PDAC with/without EUS-TA at our hospital from January 2006 to December 2021. RESULTS To examine the effect of EUS-TA on prognosis, 153 patients (122 in the EUS-TA group, 31 in the non-EUS-TA group) were analyzed. There was no significant difference in overall survival between the EUS-TA and non-EUS-TA groups after PDAC resection (P = 0.777). In univariate and multivariate analysis, preoperative EUS-TA was not identified as an independent factor related to overall survival after pancreatectomy [hazard ratio 0.96, 95 % confidence interval (CI) 0.54-1.70, P = 0.897]. Next, to examine the direct influence of EUS-TA on the results of PLC, 114 patients (83 in the EUS-TA group and 31 in the non-EUS-TA group) were analyzed. Preoperative EUS-TA was not statistically associated with positive PLC (odds ratio 0.73, 95 % CI 0.25-2.20, P = 0.583). After propensity score matching, overall survival and positive PLC were the same in both groups. CONCLUSIONS EUS-TA had no negative impact on postoperative survival and PLC-positive rates in R/BR PDAC.
Collapse
Affiliation(s)
- Motonobu Maruo
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Tsukasa Ikeura
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
| | - Ayaka Takaori
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Masatoshi Ikeda
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Koh Nakamaru
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Takashi Ito
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Masataka Masuda
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Toshiyuki Mitsuyama
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Shinji Nakayama
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Masaaki Shimatani
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Makoto Takaoka
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Nobuhiro Shibata
- Cancer Treatment Center, Kansai Medical University, Osaka, Japan
| | - Shogen Boku
- Cancer Treatment Center, Kansai Medical University, Osaka, Japan
| | - Tomoyo Yasuda
- Cancer Treatment Center, Kansai Medical University, Osaka, Japan
| | | | | | - So Yamaki
- Department of Surgery, Kansai Medical University, Osaka, Japan
| | | | - Sohei Satoi
- Department of Surgery, Kansai Medical University, Osaka, Japan; Division of Surgical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Makoto Naganuma
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| |
Collapse
|
|
14
|
Doi S, Adachi T, Watanabe A, Katsukura N, Tsujikawa T. Current perspectives on the diversification of endoscopic ultrasound-guided fine-needle aspiration and biopsy. J Med Ultrason (2001) 2024; 51:235-243. [PMID: 38108995 DOI: 10.1007/s10396-023-01393-w] [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: 08/01/2023] [Accepted: 10/23/2023] [Indexed: 12/19/2023]
Abstract
Endoscopic ultrasound-guided tissue acquisition (EUS-TA) has undergone significant advancements since it was first reported in 1992. Initially focused on the pancreas, EUS-guided fine-needle aspiration (FNA) has now been extended to encompass all organs proximal to the gastrointestinal system. Recently, a novel fine-needle biopsy (FNB) needle with an end-cut tip was developed, allowing for the collection of specimens suitable for histological assessment, a feat hard to achieve with traditional needles. The FNB needle holds promise for applications in immunohistochemistry staining and genetics evaluation, and it has the potential to yield specimens of comparable quality to core needle biopsy during percutaneous puncture, especially for lesions beyond the pancreas, such as lymph nodes. This review focuses on the efficacy of EUS-FNA/FNB for extended target regions, specifically lymph nodes, spleen, adrenal gland, and ascites. The indications for EUS-FNA have greatly expanded beyond the pancreas over the years, and future improvements and innovations in puncture needles will allow for the collection of higher-quality specimens, which is expected to play a significant part in personalized cancer treatment.
Collapse
Affiliation(s)
- Shinpei Doi
- Department of Gastroenterology, Teikyo University Mizonokuchi Hospital, 5-1-1 Futago, Takatsu-Ku, Kawasaki, Kanagawa, 213-8507, Japan.
| | - Takako Adachi
- Department of Gastroenterology, Teikyo University Mizonokuchi Hospital, 5-1-1 Futago, Takatsu-Ku, Kawasaki, Kanagawa, 213-8507, Japan
| | - Ayako Watanabe
- Department of Gastroenterology, Teikyo University Mizonokuchi Hospital, 5-1-1 Futago, Takatsu-Ku, Kawasaki, Kanagawa, 213-8507, Japan
| | - Nobuhiro Katsukura
- Department of Gastroenterology, Teikyo University Mizonokuchi Hospital, 5-1-1 Futago, Takatsu-Ku, Kawasaki, Kanagawa, 213-8507, Japan
| | - Takayuki Tsujikawa
- Department of Gastroenterology, Teikyo University Mizonokuchi Hospital, 5-1-1 Futago, Takatsu-Ku, Kawasaki, Kanagawa, 213-8507, Japan
| |
Collapse
|
|
15
|
Okuno N, Hara K. Endoscopic ultrasound-guided tissue acquisition for comprehensive genomic profiling. J Med Ultrason (2001) 2024; 51:253-260. [PMID: 38281237 DOI: 10.1007/s10396-023-01403-x] [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: 08/21/2023] [Accepted: 11/18/2023] [Indexed: 01/30/2024]
Abstract
Advances in next-generation sequencing have made comprehensive genomic profiling (CGP) using tumor tissue specimens and liquid biopsy using blood samples feasible in routine clinical practice. In the context of pancreaticobiliary cancer, it is necessary to consider CGP in formulating individualized treatment strategies. Performing CGP with tumor tissue specimens requires a sufficient number of high-quality samples. EUS-guided tissue acquisition (EUS-TA) is expected to play a significant role in this regard, and endosonographers need to address this role. Here, we review the current status of EUS-TA for CGP focusing on pancreatic cancer and biliary tract cancer.
Collapse
Affiliation(s)
- Nozomi Okuno
- Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan.
| | - Kazuo Hara
- Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan
| |
Collapse
|
|
16
|
Ishigaki K, Nakai Y, Endo G, Kurihara K, Ishida K, Tange S, Fukuda R, Takaoka S, Tokito Y, Suzuki Y, Oyama H, Kanai S, Suzuki T, Sato T, Hakuta R, Saito T, Hamada T, Takahara N, Shinozaki‐Ushiku A, Fujishiro M. Feasibility of comprehensive genomic profiling using endoscopic ultrasound-guided tissue acquisition with a 22-gauge Franseen needle. DEN OPEN 2024; 4:e365. [PMID: 38628502 PMCID: PMC11019146 DOI: 10.1002/deo2.365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 03/25/2024] [Accepted: 03/31/2024] [Indexed: 04/19/2024]
Abstract
Aim Comprehensive genomic profiling (CGP) test for solid tumors is now increasingly utilized in clinical practice, especially in pancreatobiliary cancer, and specimens obtained by endoscopic ultrasound-guided tissue acquisition (EUS-TA) are often submitted for tissue-based CGP test. In this study, we evaluated the feasibility of EUS-TA using a 22-gauge Franseen needle for the CGP test. Methods Consecutive patients with solid tumors who underwent EUS-TA using a 22-gauge Franseen needle, and whose tissue samples were pre-checked for suitability for CGP test, were included in this single-center, retrospective analysis. The success rates of appropriate sample collection for CGP evaluated by pathologists (1st quality control) and CGP test (2nd quality control) were evaluated. In addition, The EUS-TA slides were evaluated for the tissue area and tumor area content, using the image software. Results A total of 50 cases, with 78% of pancreatic cancer, were included in the analysis. A median of 3 passes of EUS-TA were performed with an adverse event rate of 4%. The success rates for 1st and 2nd quality control for CGP tests were 86% and 76%, respectively. The image analyses suggested EUS-TA specimen did not always fulfill CGP test criteria, with 18% of tissue area ≥16 mm2 and 38% of tumor area content ≥20%, even in cases with successful CGP tests. The suction method yielded a significantly larger amount of DNA but without a significant difference in the multivariate analysis. Conclusions The present study demonstrated the feasibility of EUS-TA using a 22-gauge Franseen needle for CGP test.
Collapse
Affiliation(s)
- Kazunaga Ishigaki
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
- Department of ChemotherapyThe University of Tokyo HospitalTokyoJapan
| | - Yousuke Nakai
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
- Department of Endoscopy and Endoscopic SurgeryThe University of Tokyo HospitalTokyoJapan
| | - Go Endo
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Kohei Kurihara
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Kota Ishida
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Shuichi Tange
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Rintaro Fukuda
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Shinya Takaoka
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Yurie Tokito
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Yukari Suzuki
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Hiroki Oyama
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Sachiko Kanai
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Tatsunori Suzuki
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Tatsuya Sato
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Ryunosuke Hakuta
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Tomotaka Saito
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Tsuyoshi Hamada
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Naminatsu Takahara
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | | | - Mitsuhiro Fujishiro
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
| |
Collapse
|
|
17
|
Okuwaki K, Watanabe M, Yoshida T, Tamaki A, Iwai T, Adachi K, Ishizaki J, Hanaoka T, Imaizumi H, Kida M, Kusano C. Efficacy of endoscopic ultrasound-guided tissue acquisition using stereo-microscopic on-site evaluation for possible comprehensive genome profile in patients with advanced pancreatic cancer. J Gastroenterol Hepatol 2024; 39:740-745. [PMID: 38229203 DOI: 10.1111/jgh.16478] [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: 10/31/2023] [Revised: 12/12/2023] [Accepted: 12/14/2023] [Indexed: 01/18/2024]
Abstract
BACKGROUND AND AIM Stereomicroscopic on-site evaluation (SOSE) is a rapid evaluation method for endoscopic ultrasound-guided tissue acquisition (EUS-TA) with a high diagnostic sensitivity when the stereomicroscopically visible white core (SVWC) cut-off value (≥ 11 mm) is met. We prospectively examined the association between SVWCs and the adequacy of tissue specimens, assuming subsequent comprehensive genome profiling (CGP). METHODS This study included 66 consecutive patients with suspected unresectable pancreatic cancer who underwent EUS-TA. The primary endpoint was the frequency of combined samples with ≥ 20% tumor cell content that met over twice the SVWC (T-SVWC) cut-off value, achieved through multiple punctures. The secondary endpoints were the number of punctures, the percentage of SVWC cut-off values, adverse events, the positive diagnosis rate, and the tissue section area. RESULTS The median number of EUS-TA punctures for suspected unresectable pancreatic cancer was 3 (range, 3-4); SVWC and T-SVWC cut-off values were obtained in 171/206 specimens and 65/66 patients, respectively. There were no EUS-TA-related adverse events. The positive diagnosis rate of EUS-TA was 95.5%. Among the 63 patients meeting the T-SVWC cut-off value in pathological diagnoses, the median tumor cell content was 40% (range, 5-80%), with 57 patients having tumor cell content ≥ 20%. The median tissue section area was 15 (range, 3-40) mm2. CONCLUSIONS When performing EUS-TA for unresectable pancreatic cancer with the intention of subsequent CGP, obtaining a high tumor cell content (≥ 20%) by assessing the T-SVWC cut-off value via SOSE may serve as a novel indicator for on-site estimation of CGP suitability for EUS-TA specimens.
Collapse
Affiliation(s)
- Kosuke Okuwaki
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Masafumi Watanabe
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Tsutomu Yoshida
- Division of Molecular Pathology, Department of Comprehensive Medicine, Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara, Japan
| | - Akihiro Tamaki
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Tomohisa Iwai
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Kai Adachi
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Junro Ishizaki
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Taro Hanaoka
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Hiroshi Imaizumi
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Mitsuhiro Kida
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Chika Kusano
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| |
Collapse
|
|
18
|
Ozono Y, Kawakami H, Uchiyama N, Hatada H, Ogawa S. Current status and issues in genomic analysis using EUS-FNA/FNB specimens in hepatobiliary-pancreatic cancers. J Gastroenterol 2023; 58:1081-1093. [PMID: 37698719 PMCID: PMC10590314 DOI: 10.1007/s00535-023-02037-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Accepted: 08/28/2023] [Indexed: 09/13/2023]
Abstract
Comprehensive genomic profiling based on next-generation sequencing has recently been used to provide precision medicine for various advanced cancers. Endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNA) and EUS-guided fine-needle biopsy (EUS-FNB) play essential roles in the diagnosis of abdominal masses, mainly pancreatic cancers. In recent years, CGP analysis using EUS-FNA/FNB specimens for hepatobiliary-pancreatic cancers has increased; however, the success rate of CGP analysis is not clinically satisfactory, and many issues need to be resolved to improve the success rate of CGP analysis. In this article, we review the transition from EUS-FNA to FNB, compare each test, and discuss the current status and issues in genomic analysis of hepatobiliary-pancreatic cancers using EUS-FNA/FNB specimens.
Collapse
Affiliation(s)
- Yoshinori Ozono
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan
| | - Hiroshi Kawakami
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
| | - Naomi Uchiyama
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan
| | - Hiroshi Hatada
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan
| | - Souichiro Ogawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan
| |
Collapse
|
|
19
|
Bunduc S, Varzaru B, Iacob RA, Sorop A, Manea I, Spiridon A, Chelaru R, Croitoru AE, Becheanu G, Dumbrava M, Dima S, Popescu I, Gheorghe C. Endoscopic ultrasound-guided fine-needle aspiration pancreatic adenocarcinoma samples yield adequate DNA for next-generation sequencing: A cohort analysis. World J Gastroenterol 2023; 29:2864-2874. [PMID: 37274073 PMCID: PMC10237110 DOI: 10.3748/wjg.v29.i18.2864] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 03/14/2023] [Accepted: 04/18/2023] [Indexed: 05/11/2023] Open
Abstract
BACKGROUND Genetic tests are increasingly performed for the management of unresectable pancreatic cancer. For genotyping aimed samples current guidelines recommend using core specimens, although based on moderate quality evidence. However, in clinical practice among the endoscopic ultrasound (EUS) guided tissue acquisition methods, fine needle aspiration (FNA) is the most widely performed.
AIM To assess the adequacy for next generation sequencing (NGS) of the DNA yielded from EUS-FNA pancreatic adenocarcinoma (PDAC) samples.
METHODS Between November 2018 and December 2021, 105 patients with PDAC confirmed by EUS-FNA were included in the study at our tertiary gastroenterology center. Either 22 gauge (G) or 19G FNA needles were used. One pass was dedicated to DNA extraction. DNA concentration and purity (A260/280, A260/230) were assessed by spectrophotometry. We assessed the differences in DNA parameters according to needle size and tumor characteristics (size, location) and the adequacy of the extracted DNA for NGS (defined as A260/280 ≥ 1.7, and DNA yield: ≥ 10 ng for amplicon based NGS, ≥ 50 ng for whole exome sequencing [WES], ≥ 100 ng for whole genome sequencing [WGS]) by analysis of variance and t-test respectively. Moreover, we compared DNA purity parameters across the different DNA yield categories.
RESULTS Our cohort included 49% male patients, aged 67.02 ± 8.38 years. The 22G needle was used in 71% of the cases. The DNA parameters across our samples varied as follows: DNA yield: 1289 ng (inter quartile range: 534.75-3101), A260/280 = 1.85 (1.79-1.86), A260/230 = 2.2 (1.72-2.36). DNA yield was > 10 ng in all samples and > 100 ng in 93% of them (one sample < 50 ng). There were no significant differences in the concentration and A260/280 between samples by needle size. Needle size was the only independent predictor of A260/230 which was higher in the 22G samples (P = 0.038). NGS adequacy rate was 90% for 19G samples regardless of NGS type, and for 22G samples it reached 89% for WGS adequacy and 91% for WES and amplicon based NGS. Samples with DNA yield > 100 ng had significantly higher A260/280 (1.89 ± 0.32 vs 1.34 ± 0.42, P = 0.013). Tumor characteristics were not corelated with the DNA parameters.
CONCLUSION EUS-FNA PDAC samples yield DNA adequate for subsequent NGS. DNA amount was similar between 22G and 19G FNA needles. DNA purity parameters may vary indirectly with needle size.
Collapse
Affiliation(s)
- Stefania Bunduc
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest 022328, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest 022328, Romania
| | - Bianca Varzaru
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest 022328, Romania
| | - Razvan Andrei Iacob
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest 022328, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest 022328, Romania
| | - Andrei Sorop
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest 022328, Romania
| | - Ioana Manea
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest 022328, Romania
| | - Andreea Spiridon
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest 022328, Romania
| | - Raluca Chelaru
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest 022328, Romania
| | - Adina Emilia Croitoru
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest 022328, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest 022328, Romania
| | - Gabriel Becheanu
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest 022328, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest 022328, Romania
| | - Mona Dumbrava
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest 022328, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest 022328, Romania
| | - Simona Dima
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest 022328, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest 022328, Romania
| | - Irinel Popescu
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest 022328, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest 022328, Romania
| | - Cristian Gheorghe
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest 022328, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest 022328, Romania
| |
Collapse
|
|
20
|
Kondo T, Kanai M, Matsubara J, Yamaguchi D, Ura T, Kou T, Itani T, Nomura M, Funakoshi T, Yokoyama A, Doi K, Tamaoki M, Yoshimura M, Uza N, Yamada T, Masui T, Minamiguchi S, Matsumoto S, Ishikawa H, Muto M. Association between homologous recombination gene variants and efficacy of oxaliplatin-based chemotherapy in advanced pancreatic cancer: prospective multicenter observational study. Med Oncol 2023; 40:144. [PMID: 37039943 DOI: 10.1007/s12032-023-02011-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 03/24/2023] [Indexed: 04/12/2023]
Abstract
Next-generation sequencing (NGS)-based gene profiling can identify patients with pancreatic cancer with homologous recombinant repair gene pathogenic variants (HRRv). Several retrospective studies have reported a positive association between HRRv and the efficacy of platinum-based chemotherapy. However, this association remains to be validated in a prospective study. This multicenter, prospective, observational study included patients with histologically confirmed unresectable or recurrent pancreatic cancer who required systemic chemotherapy. Patients who were oxaliplatin-naïve patients were eligible. The HRRv status was measured using a College of American Pathologists-accredited NGS panel. One-year overall survival rate (1yr-OS%) was calculated after initiation of oxaliplatin-based chemotherapy and was set as the primary endpoint. Forty patients were enrolled between August 2018 and March 2020. The NGS success rate was 95% (38/40). HRRv was detected in 11 patients (27.5%). Oxaliplatin-based chemotherapy was administered to 9 of 11 patients with HRRv (81.8%) and 15 of 29 patients with non-HRRv (51.7%). The 1yr-OS% after initiation of oxaliplatin-based chemotherapy was 44.4% [95% confidence interval (CI) 13.7-71.9] and 57.1% (95% CI 28.4-78.0) in HRRv-positive and -negative cohorts, respectively. These data suggested that HRRv status alone could not be a potential predictive marker of oxaliplatin-based chemotherapy in patients with advanced pancreatic cancer. These results were in line with the results of a recent phase II study reporting the limited efficacy of poly(adenosine diphosphate-ribose) polymerase inhibitor in patients with pancreatic cancer who harbored HRRv other than BRCA. Future studies investigating patients with biallelic HRRv in the first-line setting are warranted.Trial registration UMIN000033655.
Collapse
Affiliation(s)
- Tomohiro Kondo
- Department of Clinical Oncology, Kyoto University Hospital, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
- Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan
| | - Masashi Kanai
- Department of Clinical Oncology, Kyoto University Hospital, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan.
| | - Junichi Matsubara
- Department of Clinical Oncology, Kyoto University Hospital, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Daisuke Yamaguchi
- Department of Medical Oncology, Kyoto-Katsura Hospital, Kyoto, Japan
| | - Takashi Ura
- Department of Clinical Oncology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Tadayuki Kou
- Department of Gastroenterology and Hepatology, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan
| | - Toshinao Itani
- Department of Gastroenterology, Kobe City Nishi-Kobe Medical Center, Hyogo, Japan
| | - Motoo Nomura
- Department of Clinical Oncology, Kyoto University Hospital, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Taro Funakoshi
- Department of Clinical Oncology, Kyoto University Hospital, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Akira Yokoyama
- Department of Clinical Oncology, Kyoto University Hospital, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Keitaro Doi
- Department of Clinical Oncology, Kyoto University Hospital, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Masashi Tamaoki
- Department of Clinical Oncology, Kyoto University Hospital, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Michio Yoshimura
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Norimitsu Uza
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Takahiro Yamada
- Clinical Genetics Unit, Kyoto University Hospital, Kyoto, Japan
- Division of Clinical Genetics, Hokkaido University Hospital, Hokkaido, Japan
| | - Toshihiko Masui
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | | | - Shigemi Matsumoto
- Department of Clinical Oncology, Kyoto University Hospital, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| | - Hideki Ishikawa
- Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Manabu Muto
- Department of Clinical Oncology, Kyoto University Hospital, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
| |
Collapse
|
|
21
|
Hijioka S, Nagashio Y, Maruki Y, Kawasaki Y, Takeshita K, Morizane C, Okusaka T. Endoscopic Ultrasound-Guided Tissue Acquisition of Pancreaticobiliary Cancer Aiming for a Comprehensive Genome Profile. Diagnostics (Basel) 2023; 13:diagnostics13071275. [PMID: 37046493 PMCID: PMC10093621 DOI: 10.3390/diagnostics13071275] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 03/24/2023] [Accepted: 03/27/2023] [Indexed: 03/30/2023] Open
Abstract
In recent years, cancer genomic medicine centered on comprehensive genome profile (CGP) analysis has become widely used in the field of pancreatic cancer. Endoscopic ultrasound-guided tissue acquisition (EUS-TA) has played an important role in pancreatic cancer, and recently, more EUS-TA tissue samples are considered for CGP analysis. Differences exist between the Oncoguide NCC Oncopanel System and Foundation One CDx Cancer Genome Profile, which are CGP tests approved by insurance programs in Japan, including the analysis criteria, optimal needle selection for meeting these criteria, and puncture target. It is important to understand not only the specimen collection factors, but also the specimen processing factors that can increase the success rate of CGP testing. Furthermore, cancer genome medicine is expected to enter an era of increasing turbulence in the future, and endoscopists need to respond flexibly to these changes. Herein, we review the current status of cancer genome medicine in pancreatic and biliary tract cancers and cancer gene panel testing using EUS-TA.
Collapse
|
|
22
|
Lin MY, Wu CL, Su YY, Huang CJ, Chang WL, Sheu BS. Tissue Quality Comparison Between Heparinized Wet Suction and Dry Suction in Endoscopic Ultrasound-Fine Needle Biopsy of Solid Pancreatic Masses: A Randomized Crossover Study. Gut Liver 2023; 17:318-327. [PMID: 36052613 PMCID: PMC10018294 DOI: 10.5009/gnl220030] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 04/19/2022] [Accepted: 05/13/2022] [Indexed: 11/04/2022] Open
Abstract
Background/Aims A high-quality sample allows for next-generation sequencing and the administration of more tailored precision medicine treatments. We aimed to evaluate whether heparinized wet suction can obtain higher quality samples than the standard dry-suction method during endoscopic ultrasound (EUS)-guided biopsy of pancreatic masses. Methods A prospective randomized crossover study was conducted. Patients with a solid pancreatic mass were randomly allocated to receive either heparinized wet suction first or dry suction first. For each method, two needle passes were made, followed by a switch to the other method for a total of four needle punctures. The primary outcome was the aggregated white tissue length. Histological blood contamination, diagnostic performance and adverse events were analyzed as secondary outcomes. In addition, the correlation between white tissue length and the extracted DNA amount was analyzed. Results A total of 50 patients were enrolled, and 200 specimens were acquired (100 with heparinized wet suction and 100 with dry suction), with one minor bleeding event. The heparinized wet suction approach yielded specimens with longer aggregated white tissue length (11.07 mm vs 7.96 mm, p=0.001) and less blood contamination (p=0.008). A trend towards decreasing tissue quality was observed for the 2nd pass of the dry-suction method, leading to decreased diagnostic sensitivity and accuracy, although the accumulated diagnostic performance was comparable between the two suction methods. The amount of extracted DNA correlated positively to the white tissue length (p=0.001, Spearman̕s ρ=0.568). Conclusions Heparinized wet suction for EUS tissue acquisition of solid pancreatic masses can yield longer, bloodless, DNA-rich tissue without increasing the incidence of adverse events (ClinicalTrials.gov. identifier NCT04707560).
Collapse
Affiliation(s)
- Meng-Ying Lin
- Departments of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University College of Medicine, Tainan, Taiwan
| | - Cheng-Lin Wu
- Departments of Pathology, National Cheng Kung University Hospital, National Cheng Kung University College of Medicine, Tainan, Taiwan
| | - Yung-Yeh Su
- Departments of Oncology, National Cheng Kung University Hospital, National Cheng Kung University College of Medicine, Tainan, Taiwan.,National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
| | - Chien-Jui Huang
- Departments of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University College of Medicine, Tainan, Taiwan
| | - Wei-Lun Chang
- Departments of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University College of Medicine, Tainan, Taiwan
| | - Bor-Shyang Sheu
- Departments of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University College of Medicine, Tainan, Taiwan
| |
Collapse
|
|
23
|
Takeshita K, Hijioka S, Nagashio Y, Maruki Y, Kawasaki Y, Maehara K, Murashima Y, Okada M, Ikeda G, Yamada N, Takasaki T, Agarie D, Hara H, Hagiwara Y, Okamoto K, Yamashige D, Ohba A, Kondo S, Morizane C, Ueno H, Saito Y, Ohe Y, Okusaka T. Diagnostic Ability of Endoscopic Ultrasound-Guided Tissue Acquisition Using 19-Gauge Fine-Needle Biopsy Needle for Abdominal Lesions. Diagnostics (Basel) 2023; 13:diagnostics13030450. [PMID: 36766558 PMCID: PMC9914510 DOI: 10.3390/diagnostics13030450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 01/20/2023] [Accepted: 01/23/2023] [Indexed: 01/28/2023] Open
Abstract
Attempts at performing endoscopic ultrasound-guided tissue acquisition (EUS-TA) with a 19G needle are increasing because histological diagnosis and comprehensive genomic profiling are a necessity. However, the diagnostic ability of the 19G fine-needle biopsy (FNB) needle, especially the third-generation FNB needle, is unclear and has been retrospectively reviewed. The 19G TopGain needle was used in 147 patients and 160 lesions between September 2020 and December 2021. The technical success rate of the biopsies was 99.4% (159/160). The early adverse event rate was 4.1% (6/147), and moderate or severe adverse event rate occurrence was 2.0% (3/147). The sensitivity, specificity, and accuracy of the 19G TopGain needle for 157 lesions with a confirmed diagnosis were 96.7%, 100%, and 96.8%, respectively. Rescue EUS-TA using the 19G TopGain needle was performed for nine lesions, and a successful diagnosis was made in six of these lesions (66.7%). The diagnostic ability of EUS-TA using the third-generation 19G TopGain needle was favorable. However, the use of 19G FNB needles may increase adverse events. Therefore, EUS-TA with a 19G FNB needle is mainly indicated in lesions where comprehensive genomic profiling may be necessary or the diagnosis could not be determined via EUS-TA using the 22G needle.
Collapse
Affiliation(s)
- Kotaro Takeshita
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
- Cancer Medicine, Jikei University Graduate School of Medicine, Tokyo 105-0003, Japan
| | - Susumu Hijioka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
- Correspondence: ; Tel.: +81-3-3542-2511
| | - Yoshikuni Nagashio
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Yuta Maruki
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Yuki Kawasaki
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Kosuke Maehara
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Yumi Murashima
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Mao Okada
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Go Ikeda
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Natsumi Yamada
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Tetsuro Takasaki
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Daiki Agarie
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Hidenobu Hara
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Yuya Hagiwara
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Kohei Okamoto
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Daiki Yamashige
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Akihiro Ohba
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Shunsuke Kondo
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Chigusa Morizane
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Hideki Ueno
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Yutaka Saito
- Endoscopy Division, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Yuichiro Ohe
- Cancer Medicine, Jikei University Graduate School of Medicine, Tokyo 105-0003, Japan
- Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Takuji Okusaka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| |
Collapse
|
|
24
|
Ikeda G, Hijioka S, Nagashio Y, Maruki Y, Ohba A, Hisada Y, Yoshinari M, Harai S, Kitamura H, Koga T, Murashima Y, Maehara K, Okada M, Yamashige D, Okamoto K, Hara H, Hagiwara Y, Agarie D, Takasaki T, Takeshita K, Kawasaki Y, Kondo S, Morizane C, Ueno H, Hiraoka N, Yatabe Y, Saito Y, Iwakiri K, Okusaka T. Fine-needle biopsy with 19G needle is effective in combination with endoscopic ultrasound-guided tissue acquisition for genomic profiling of unresectable pancreatic cancer. Dig Endosc 2023; 35:124-133. [PMID: 35993898 DOI: 10.1111/den.14423] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 08/18/2022] [Indexed: 01/17/2023]
Abstract
OBJECTIVES Comprehensive genomic profiling (CGP) has been approved in Japan since June 2019, enabling mutation-specific therapy. Although tissue sampling via endoscopic ultrasound-guided tissue acquisition (EUS-TA) is standard in pancreatic cancer, reports on obtaining appropriate samples for CGP, especially for the OncoGuide NCC Oncopanel System (NOP) and FoundationOne CDx (FOne), are lacking. Therefore, we investigated the success rate and factors related to appropriate EUS-TA sampling for CGP analysis suitability in unresectable pancreatic ductal adenocarcinoma (UR-PDAC). METHODS Participants comprised 150 UR-PDAC patients who underwent EUS-TA and tumor sample evaluation for CGP analysis suitability between June 2019 and December 2021. The proportion of patients meeting the criteria was evaluated considering tumor size, puncture lesion, presence of metastasis, type and size of puncture needle, suction method, number of punctures, and puncture route. RESULTS In total, 39.2% (60/153) of samples met NOP analysis suitability criteria and 0% met FOne analysis suitability criteria. The suitability rate was significantly higher with 19G fine-needle biopsy (FNB) (56.0%; 42/75) than with 22G FNB (32.6%; 14/43) and 22G fine-needle aspiration (11.4%; 4/35). Nineteen-gauge needle (odds ratio [OR] 2.53; 95% confidence interval [CI] 1.15-5.57; P = 0.021) and FNB (OR 3.57; 95% CI 1.05-12.20; P = 0.041) were independent factors contributing to NOP analysis suitability. Among 30 patients who underwent actual NOP analysis, the analysis success rate was 100% (30/30). CONCLUSION In sample collection via EUS-TA, 19G and FNB needles contribute to NOP analysis suitability.
Collapse
Affiliation(s)
- Go Ikeda
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
- Department of Gastroenterology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan
| | - Susumu Hijioka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Yoshikuni Nagashio
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Yuta Maruki
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Akihiro Ohba
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Yuya Hisada
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Motohiro Yoshinari
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Shota Harai
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Hidetoshi Kitamura
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Takehiko Koga
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Yumi Murashima
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Kosuke Maehara
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Mao Okada
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Daiki Yamashige
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Kohei Okamoto
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Hidenobu Hara
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Yuya Hagiwara
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Daiki Agarie
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Tetsuro Takasaki
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Kotaro Takeshita
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Yuki Kawasaki
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Shunsuke Kondo
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Chigusa Morizane
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Hideki Ueno
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Nobuyoshi Hiraoka
- Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan
| | - Yasushi Yatabe
- Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan
| | - Yutaka Saito
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Katsuhiko Iwakiri
- Department of Gastroenterology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan
| | - Takuji Okusaka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| |
Collapse
|
|
25
|
Ashida R, Kitano M. Endoscopic ultrasound-guided tissue acquisition for pancreatic ductal adenocarcinoma in the era of precision medicine. Dig Endosc 2022; 34:1329-1339. [PMID: 35488448 DOI: 10.1111/den.14344] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Accepted: 04/27/2022] [Indexed: 12/13/2022]
Abstract
Endoscopic ultrasound-guided tissue acquisition (EUS-TA) currently plays a central role in the diagnosis of pancreatic ductal adenocarcinoma (PDAC). Although fine-needle aspiration has been the gold standard, novel biopsy needles for fine-needle biopsy (FNB) were developed to overcome its limitations, which include low tumor cellularity and the inability to retain cellular architecture. Following recent improvements in FNB needles, the pathological diagnosis has shifted from cytology to histology and now to genetic diagnosis. Genetic analysis using EUS-TA samples began with a search for the presence of K-ras mutations. However, the introduction of next-generation sequencers has dramatically changed genetic analysis and led to the gradual elucidation of the mechanism of PDAC, enabling personalized medicine by performing multiple gene analyses simultaneously. Comprehensive genomic profiling is currently applied in the clinical setting and there is an increasing need for gene analysis using EUS-TA samples. Although target genome sequencing is feasible even with cytological specimens, it can be difficult to proceed with full genetic analysis including whole-exome sequence or whole-genome sequence if the samples are too small. Genetic analysis will become highly important in determining indications for personalized medicine such as poly (ADP-ribose) polymerase inhibitors or immune checkpoint inhibitors. Therefore, the endosonographer must always take gene analysis into consideration when collecting samples for diagnosis and further improvement of the puncture technique and needle development are anticipated in the future.
Collapse
Affiliation(s)
- Reiko Ashida
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Masayuki Kitano
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| |
Collapse
|
|
26
|
Ohno E, Kawashima H, Ishikawa T, Mizutani Y, Iida T, Nishio R, Uetsuki K, Yashika J, Yamada K, Yoshikawa M, Gibo N, Aoki T, Kataoka K, Mori H, Takada Y, Aoi H, Takahashi H, Yamamura T, Furukawa K, Nakamura M, Shimoyama Y, Hirooka Y, Fujishiro M. The role of EUS elastography-guided fine needle biopsy in the histological diagnosis of solid pancreatic lesions: a prospective exploratory study. Sci Rep 2022; 12:16603. [PMID: 36198904 PMCID: PMC9535001 DOI: 10.1038/s41598-022-21178-4] [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: 03/01/2022] [Accepted: 09/23/2022] [Indexed: 11/09/2022] Open
Abstract
This study aimed to evaluate the feasibility and efficacy of Endoscopic ultrasound elastography-guided fine needle biopsy (EUS-EG-FNB) for the diagnosis of pancreatic mass lesions. EUS-EG images were classified into heterogeneous and homogeneous groups. For the heterogeneous group, EUS-FNB was separately performed in both hard areas and soft areas. Only samples obtained during the first two passes (hard/soft areas) were used to compare the diagnostic accuracy as well as the quality and quantity of the specimens. We investigated the association of EUS-EG findings using strain histogram analysis with the histological findings. Fifty-five patients were enrolled including 25 patients with heterogeneous group. The homogeneous group had significantly lower mean strain value (hard) lesions. The adequate sampling rates from hard and soft areas were 88 and 92%, respectively (P = 0.6374). Comparison of the diagnostic accuracy and the quality and quantity of the histological core between hard and soft areas showed no significant differences. In pancreatic adenocarcinoma cases, the proportion of fibrous stroma in the core tissue was significantly correlated with the elasticity of the region. (R2 = 0.1226: P = 0.0022) EUS-EG may reflect tissue composition in pancreatic tumors, however, EUS-EG did not affect either the quality and quantity of the tissues obtained. Clinical Trial Registry No: UMIN-000033073.
Collapse
Affiliation(s)
- Eizaburo Ohno
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
| | - Hiroki Kawashima
- Department of Endoscopy, Nagoya University Hospital, Nagoya, Aichi, Japan
| | - Takuya Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Yasuyuki Mizutani
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Tadashi Iida
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Ryo Nishio
- Department of Gastroenterology, Nakatsugawa Municipal Hospital, Gifu, Japan
| | - Kota Uetsuki
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Jun Yashika
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Kenta Yamada
- Department of Endoscopy, Nagoya University Hospital, Nagoya, Aichi, Japan
| | - Masakatsu Yoshikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Noriaki Gibo
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Toshinori Aoki
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Kunio Kataoka
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Hiroshi Mori
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Yoshihisa Takada
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Hironori Aoi
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Hidekazu Takahashi
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Takeshi Yamamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Kazuhiro Furukawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Masanao Nakamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Yoshie Shimoyama
- Department of Pathology and Laboratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
| | - Yoshiki Hirooka
- Department of Gastroenterology and Hepatology, Fujita Health University, Toyoake, Aichi, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| |
Collapse
|
|
27
|
Yokoyama S, Iwaya H, Akahane T, Hamada T, Higashi M, Hashimoto S, Tanoue S, Ohtsuka T, Ido A, Tanimoto A. Sequential evaluation of
MUC
promoter methylation using next‐generation sequencing‐based custom‐made panels in liquid‐based cytology specimens of pancreatic cancer. Diagn Cytopathol 2022; 50:499-507. [DOI: 10.1002/dc.25022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Accepted: 07/12/2022] [Indexed: 11/06/2022]
Affiliation(s)
- Sieya Yokoyama
- Department of Pathology Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan
| | - Hiromichi Iwaya
- Digestive and Lifestyle Diseases Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan
| | - Toshiaki Akahane
- Department of Pathology Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan
- Center for Human Genome and Gene Analysis Kagoshima University Hospital Kagoshima Japan
| | - Taiji Hamada
- Department of Pathology Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan
| | - Michiyo Higashi
- Unit of Surgical Pathology Kagoshima University Hospital Kagoshima Japan
| | - Shinichi Hashimoto
- Digestive and Lifestyle Diseases Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan
| | - Shiroh Tanoue
- Digestive and Lifestyle Diseases Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan
| | - Takao Ohtsuka
- Department of Digestive Surgery, Breast and Thyroid Surgery Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan
| | - Akio Ido
- Digestive and Lifestyle Diseases Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan
| | - Akihide Tanimoto
- Department of Pathology Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan
- Center for Human Genome and Gene Analysis Kagoshima University Hospital Kagoshima Japan
- Unit of Surgical Pathology Kagoshima University Hospital Kagoshima Japan
| |
Collapse
|
|
28
|
Paik WH. Endoscopic ultrasound-guided tissue acquisition: Needle types, technical issues, and sample handling. INTERNATIONAL JOURNAL OF GASTROINTESTINAL INTERVENTION 2022. [DOI: 10.18528/ijgii220019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Woo Hyun Paik
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| |
Collapse
|
|
29
|
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.
Collapse
|
|
30
|
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.
Collapse
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
| | | |
Collapse
|
|
31
|
Itonaga M, Ashida R, Murata SI, Yamashita Y, Hatamaru K, Tamura T, Kawaji Y, Kayama Y, Emori T, Kawai M, Yamaue H, Matsuzaki I, Nagai H, Kinoshita Y, Wan K, Shimokawa T, Kitano M. Kras Gene Analysis Using Liquid-Based Cytology Specimens Predicts Therapeutic Responses and Prognosis in Patients with Pancreatic Cancer. Cancers (Basel) 2022; 14:cancers14030551. [PMID: 35158819 PMCID: PMC8833456 DOI: 10.3390/cancers14030551] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 01/08/2022] [Accepted: 01/21/2022] [Indexed: 02/04/2023] Open
Abstract
Simple Summary New therapeutic strategies are needed to improve the prognosis of pancreatic ductal adenocarcinoma (PDAC) and developing biomarkers that can guide individualized treatment decisions is an important part of these strategies. In this study, we found that unresectable PDAC patients harboring wild-type Kras had significantly longer progression-free survival (PFS) and overall survival (OS) than those harboring mutant Kras after undergoing first-line gemcitabine and nab-paclitaxel (GA) therapy and that wild-type Kras was a significant predictor of longer PFS and OS. This is the first report suggesting that Kras gene analysis has the potential to predict therapeutic responses to GA and the prognosis of unresectable PDAC. Abstract Background: Although several molecular analyses have shown that the Kras gene status is related to long-term survival of patients with pancreatic ductal adenocarcinoma (PDAC), the results remain controversial. Here, we examined the Kras gene status in a cohort of unresectable PDAC patients who underwent first-line therapy with gemcitabine and nab-paclitaxel (GA) and assessed differences in chemotherapy responses and survival. Methods: Patients with a histological diagnosis of PDAC (based on EUS-guided fine-needle aspiration) from 2017 to 2019 were enrolled. Tumor genomic DNA was extracted from residual liquid-based cytology specimens and Kras mutations were assessed using the quenching probe method. The relationships between the Kras status and progression-free survival (PFS) and overall survival (OS) were assessed. Results: Of the 110 patients analyzed, 15 had wild-type Kras. Those with the wild-type gene showed significantly longer PFS and OS than those with mutant Kras (6.9/5.3 months (p = 0.044) vs. 19.9/11.8 months (p = 0.037), respectively). Multivariate analyses identified wild-type Kras as a significant independent factor associated with longer PFS and OS (HR = 0.53 (p = 0.045) and HR = 0.35 (p = 0.007), respectively). Conclusions: The analysis of the Kras gene status could be used to predict therapeutic responses to GA and prognosis in unresectable PDAC patients.
Collapse
Affiliation(s)
- Masahiro Itonaga
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama 641-0012, Japan; (M.I.); (Y.Y.); (K.H.); (T.T.); (Y.K.); (Y.K.); (T.E.); (M.K.)
| | - Reiko Ashida
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama 641-0012, Japan; (M.I.); (Y.Y.); (K.H.); (T.T.); (Y.K.); (Y.K.); (T.E.); (M.K.)
- Correspondence:
| | - Shin-Ichi Murata
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama 641-0012, Japan; (S.-I.M.); (M.K.); (H.Y.)
| | - Yasunobu Yamashita
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama 641-0012, Japan; (M.I.); (Y.Y.); (K.H.); (T.T.); (Y.K.); (Y.K.); (T.E.); (M.K.)
| | - Keiichi Hatamaru
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama 641-0012, Japan; (M.I.); (Y.Y.); (K.H.); (T.T.); (Y.K.); (Y.K.); (T.E.); (M.K.)
| | - Takashi Tamura
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama 641-0012, Japan; (M.I.); (Y.Y.); (K.H.); (T.T.); (Y.K.); (Y.K.); (T.E.); (M.K.)
| | - Yuki Kawaji
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama 641-0012, Japan; (M.I.); (Y.Y.); (K.H.); (T.T.); (Y.K.); (Y.K.); (T.E.); (M.K.)
| | - Yuudai Kayama
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama 641-0012, Japan; (M.I.); (Y.Y.); (K.H.); (T.T.); (Y.K.); (Y.K.); (T.E.); (M.K.)
| | - Tomoya Emori
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama 641-0012, Japan; (M.I.); (Y.Y.); (K.H.); (T.T.); (Y.K.); (Y.K.); (T.E.); (M.K.)
| | - Manabu Kawai
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama 641-0012, Japan; (S.-I.M.); (M.K.); (H.Y.)
| | - Hiroki Yamaue
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama 641-0012, Japan; (S.-I.M.); (M.K.); (H.Y.)
| | - Ibu Matsuzaki
- Department of Human Pathology, Wakayama Medical University, Wakayama 641-0012, Japan; (I.M.); (H.N.); (Y.K.)
| | - Hirokazu Nagai
- Department of Human Pathology, Wakayama Medical University, Wakayama 641-0012, Japan; (I.M.); (H.N.); (Y.K.)
| | - Yuichi Kinoshita
- Department of Human Pathology, Wakayama Medical University, Wakayama 641-0012, Japan; (I.M.); (H.N.); (Y.K.)
| | - Ke Wan
- Clinical Study Support Center, Wakayama Medical University, Wakayama 641-0012, Japan; (K.W.); (T.S.)
| | - Toshio Shimokawa
- Clinical Study Support Center, Wakayama Medical University, Wakayama 641-0012, Japan; (K.W.); (T.S.)
| | - Masayuki Kitano
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama 641-0012, Japan; (M.I.); (Y.Y.); (K.H.); (T.T.); (Y.K.); (Y.K.); (T.E.); (M.K.)
| |
Collapse
|
|
32
|
Nikas IP, Mountzios G, Sydney GI, Ioakim KJ, Won JK, Papageorgis P. Evaluating Pancreatic and Biliary Neoplasms with Small Biopsy-Based Next Generation Sequencing (NGS): Doing More with Less. Cancers (Basel) 2022; 14:cancers14020397. [PMID: 35053560 PMCID: PMC8773813 DOI: 10.3390/cancers14020397] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 01/05/2022] [Accepted: 01/10/2022] [Indexed: 12/13/2022] Open
Abstract
Simple Summary Pancreatic cancer and cholangiocarcinoma are aggressive diseases mostly diagnosed at an advanced and inoperable stage. This review presents the value of next-generation sequencing (NGS) when performed on small biopsies—including fine-needle aspiration/biopsy samples, brushings, pancreatic juice and bile, and also blood—in the field of pancreatobiliary neoplasia. NGS could guide physicians while evaluating pancreatic solid and cystic lesions or suspicious biliary strictures, performing surveillance in high-risk individuals, or monitoring the disease and assessing prognosis in already diagnosed cancer patients. Evidence suggests that NGS performed on small biopsies is a robust tool for the diagnosis and pre-operative risk stratification of pancreatic and biliary lesions, whereas it also carries significant prognostic and therapeutic value. However, effective standardization of the pre-analytical and analytical assay parameters used for each clinical scenario is needed to fully implement NGS into routine practice and provide more personalized management in patients with suspected or established pancreatobiliary neoplasia. Abstract Pancreatic cancer and cholangiocarcinoma are lethal diseases mainly diagnosed at an inoperable stage. As pancreatobiliary surgical specimens are often unavailable for further molecular testing, this review aimed to highlight the diagnostic, prognostic, and therapeutic impact of next-generation sequencing (NGS) performed on distinct small biopsies, including endoscopic ultrasound fine-needle aspirations and biopsies of pancreatic solid and cystic lesions, biliary duct brushings, and also “liquid biopsies” such as the pancreatic juice, bile, and blood. NGS could clarify indeterminate pancreatic lesions or biliary strictures, for instance by identifying TP53 or SMAD4 mutations indicating high-grade dysplasia or cancer. It could also stratify pancreatic cystic lesions, by distinguishing mucinous from non-mucinous cysts and identifying high-risk cysts that should be excised in surgically fit patients, whereas the combination of cytology, elevated cystic CEA levels and NGS could improve the overall diagnostic accuracy. When NGS is performed on the pancreatic juice, it could stratify high-risk patients under surveillance. On the plasma, it could dynamically monitor the disease course and response to therapy. Notably, the circulating tumor DNA (ctDNA) levels have been associated with staging, grading, and survival. Lastly, NGS has shown potential in identifying potentially actionable molecular alterations. In conclusion, NGS applied on small biopsies could carry significant diagnostic, prognostic, and therapeutic value.
Collapse
Affiliation(s)
- Ilias P. Nikas
- School of Medicine, European University Cyprus, Nicosia 2404, Cyprus; (G.I.S.); (K.J.I.)
- Correspondence:
| | - Giannis Mountzios
- Fourth Department of Medical Oncology and Clinical Trials Unit, Henry Dunant Hospital Center, 11526 Athens, Greece;
| | - Guy I. Sydney
- School of Medicine, European University Cyprus, Nicosia 2404, Cyprus; (G.I.S.); (K.J.I.)
- Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62702, USA
| | - Kalliopi J. Ioakim
- School of Medicine, European University Cyprus, Nicosia 2404, Cyprus; (G.I.S.); (K.J.I.)
- Department of Internal Medicine, Limassol General Hospital, Limassol 4131, Cyprus
| | - Jae-Kyung Won
- Department of Pathology, Seoul National University Hospital and College of Medicine, Seoul 03080, Korea;
| | - Panagiotis Papageorgis
- Tumor Microenvironment, Metastasis and Experimental Therapeutics Laboratory, Basic and Translational Cancer Research Center, Department of Life Sciences, European University Cyprus, Nicosia 2404, Cyprus;
| |
Collapse
|
|
33
|
Sunami K, Bando H, Yatabe Y, Naito Y, Takahashi H, Tsuchihara K, Toyooka S, Mimori K, Kohsaka S, Uetake H, Kinoshita I, Komine K, Takeda M, Hayashida T, Tamura K, Nishio K, Yamamoto N. Appropriate use of cancer comprehensive genome profiling assay using circulating tumor DNA. Cancer Sci 2021; 112:3911-3917. [PMID: 34128569 PMCID: PMC8409307 DOI: 10.1111/cas.15022] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Revised: 06/08/2021] [Accepted: 06/09/2021] [Indexed: 01/11/2023] Open
Abstract
Comprehensive genomic profiling (CGP) is being increasingly used for the routine clinical management of solid cancers. In July 2018, the use of tumor tissue-based CGP assays became available for all solid cancers under the universal health insurance system in Japan. Several restrictions presently exist, such as patient eligibility and limitations on the opportunities to perform such assays. The clinical implementation of CGP based on plasma circulating tumor DNA (ctDNA) is also expected to raise issues regarding the selection and use of tissue DNA and ctDNA CGP. A Joint Task Force for the Promotion of Cancer Genome Medicine comprised of three Japanese cancer-related societies has formulated a policy proposal for the appropriate use of plasma CGP (in Japanese), available at https://www.jca.gr.jp/researcher/topics/2021/files/20210120.pdf, http://www.jsco.or.jp/jpn/user_data/upload/File/20210120.pdf, and https://www.jsmo.or.jp/file/dl/newsj/2765.pdf. Based on these recommendations, the working group has summarized the respective advantages and cautions regarding the use of tissue DNA CGP and ctDNA CGP with reference to the advice of a multidisciplinary expert panel, the preferred use of plasma specimens over tissue, and multiple ctDNA testing. These recommendations have been prepared to maximize the benefits of performing CGP assays and might be applicable in other countries and regions.
Collapse
Affiliation(s)
- Kuniko Sunami
- Department of Laboratory MedicineNational Cancer Center HospitalTokyoJapan
| | - Hideaki Bando
- Department of Clinical OncologyAichi Cancer Center HospitalNagoyaJapan
| | - Yasushi Yatabe
- Department of Diagnostic PathologyNational Cancer Center HospitalDivision of Molecular PathologyNational Cancer Center Research InstituteTokyoJapan
| | - Yoichi Naito
- Department of Medical OncologyNational Cancer Center Hospital EastKashiwaJapan
| | - Hideaki Takahashi
- Department of Hepatobiliary and Pancreatic OncologyNational Cancer Center Hospital EastKashiwaJapan
| | - Katsuya Tsuchihara
- Division of Translational InformaticsExploratory Oncology Research and Clinical Trial CenterNational Cancer CenterKashiwaJapan
| | - Shinichi Toyooka
- Department of General Thoracic Surgery and Breast and Endocrine SurgeryOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesOkayamaJapan
| | | | - Shinji Kohsaka
- Division of Cellular SignalingNational Cancer Center Research InstituteTokyoJapan
| | - Hiroyuki Uetake
- Department of Clinical ResearchNational Disaster Medical CenterTokyoJapan
| | - Ichiro Kinoshita
- Division of Clinical Cancer GenomicsHokkaido University HospitalSapporoJapan
| | - Keigo Komine
- Department of Clinical OncologyTohoku University HospitalSendaiJapan
| | - Masayuki Takeda
- Department of Cancer Genomics and Medical OncologyNara Medical UniversityNaraJapan
| | - Tetsu Hayashida
- Department of SurgeryKeio University School of MedicineTokyoJapan
| | - Kenji Tamura
- Department of Medical OncologyShimane University HospitalIzumoJapan
| | - Kazuto Nishio
- Department of Genome BiologyKindai University Faculty of MedicineOsakasayamaJapan
| | - Noboru Yamamoto
- Department of Experimental TherapeuticsNational Cancer Center HospitalTokyoJapan
| | | |
Collapse
|
|
34
|
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.
Collapse
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.)
| | | | | | | | | | | | | | | |
Collapse
|
|
35
|
Feasibility of BRCA1/2 Testing of Formalin-Fixed and Paraffin-Embedded Pancreatic Tumor Samples: A Consecutive Clinical Series. Diagnostics (Basel) 2021; 11:diagnostics11061046. [PMID: 34200245 PMCID: PMC8227758 DOI: 10.3390/diagnostics11061046] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 05/24/2021] [Accepted: 06/02/2021] [Indexed: 12/24/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer, with most patients diagnosed at advanced stages. First-line treatment based on a combined chemotherapy (FOLFIRINOX or gemcitabine plus nab-paclitaxel) provides limited benefits. Olaparib, a PARP inhibitor, has been approved as maintenance for PDAC patients harboring germline BRCA1/2 pathogenic mutations and previously treated with a platinum-based chemotherapy. BRCA1/2 germline testing is recommended, but also somatic mutations could predict responses to PARP inhibitors. Analysis of tumor tissues can detect both germline and somatic mutations and potential resistance alterations. Few data are available about BRCA1/2 testing on pancreatic tumor tissues, which often include limited biological material. We performed BRCA1/2 testing, by an amplicon-based Next Generation Sequencing (NGS) panel, on 37 consecutive PDAC clinical samples: 86.5% of cases were adequate for NGS analysis, with a success rate of 81.2% (median DNA input: 10 nanograms). Three BRCA2 mutations were detected (11.5%). Failed samples were all from tissue macrosections, which had higher fragmented DNA than standard sections, biopsies and fine-needle aspirations, likely due to fixation procedures. BRCA1/2 testing on pancreatic tumor tissues can also be feasible on small biopsies, but more cases must be analyzed to define its role and value in the PDAC diagnostic algorithm.
Collapse
|
|
36
|
Kandel P, Nassar A, Gomez V, Raimondo M, Woodward TA, Crook JE, Fares NS, Wallace MB. Comparison of endoscopic ultrasound-guided fine-needle biopsy versus fine-needle aspiration for genomic profiling and DNA yield in pancreatic cancer: a randomized crossover trial. Endoscopy 2021; 53:376-382. [PMID: 32767288 DOI: 10.1055/a-1223-2171] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND National guidelines recommend genomic profiling of tumor tissue to guide precision therapy. We compared the specimen adequacy for genomic profiling and yield of DNA between endoscopic ultrasound (EUS)-guided fine-needle biopsy (FNB) and EUS-guided fine-needle aspiration (FNA). METHODS In our tandem, randomized controlled trial, consecutive patients undergoing EUS for evaluation of pancreatic masses underwent both conventional EUS-FNA with a 25-gauge needle and paired EUS-FNB (19 or 22-gauge needle), with the order randomized (EUS-FNA first followed by EUS-FNB, or vice versa). A minimum of one pass with each needle was obtained for histology. Second and third passes were performed to collect DNA. Specimens were evaluated by a cytopathologist blinded to the needle type. Specimen adequacy for genomic profiling was calculated based on FoundationOne clinical diagnostic (CDx) adequacy requirements. We compared the adequacy for genomic profiling DNA (quantity) and histology yields with both needles. RESULTS Analysis included 50 patients (25 men; mean age 68 [standard deviation (SD) 13] years), with a mean lesion size of 38 (SD 17) mm; 37 lesions (74 %) were pancreatic ductal adenocarcinoma (PDAC). The mean DNA concentrations in PDAC by FNB and FNA needles were 5.930 (SD 0.881) µg/mL vs. 3.365 (SD 0.788) µg/mL, respectively (P = 0.01). The median standardized histology score per pass with EUS-FNB was 5 (sufficient for histology) and for EUS-FNA was 2 (enough for cytology). Specimen adequacy for genomic profiling and yield of DNA was significantly higher with FNB than with FNA needles. CONCLUSIONS In this study, adequacy for genomic profiling, DNA, and histology yield were considerably superior using an EUS-FNB needle compared with an EUS-FNA needle.
Collapse
Affiliation(s)
- Pujan Kandel
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Aziza Nassar
- Department of Laboratory Medicine & Pathology, Mayo Clinic, Jacksonville, Florida, USA
| | - Victoria Gomez
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Massimo Raimondo
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Timothy A Woodward
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Julia E Crook
- Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida, USA
| | - Natalie S Fares
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Michael B Wallace
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| |
Collapse
|
|
37
|
Carrara S, Soldà G, Di Leo M, Rahal D, Peano C, Giunta M, Lamonaca L, Auriemma F, Anderloni A, Fugazza A, Maselli R, Malesci A, Laghi L, Repici A. Side-by-side comparison of next-generation sequencing, cytology, and histology in diagnosing locally advanced pancreatic adenocarcinoma. Gastrointest Endosc 2021; 93:597-604.e5. [PMID: 32640200 DOI: 10.1016/j.gie.2020.06.069] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Accepted: 06/26/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS EUS-guided biopsy sampling is the method of choice for obtaining pancreatic tissue. Next-generation sequencing (NGS) has been applied to EUS-guided biopsy sampling and may classify patients based on specific molecular profiles. Our study aimed to compare side-by-side the diagnostic yield achievable by genetic identification of somatic mutations detected with NGS versus histologic and cytologic typing in locally advanced pancreatic carcinoma (LAPC) in samples acquired under EUS guidance. METHODS We conducted a prospective comparative pilot study at Humanitas Research Hospital. The study included 33 patients referred for LAPC who underwent EUS-guided tissue acquisition using a 22-gauge Franseen needle. Material was obtained for both pathologic diagnosis and DNA extraction and targeted NGS analysis with the AmpliSeq Comprehensive Panel v3 (Illumina Inc, San Diego, Calif, USA). Twenty-one genes were prioritized for somatic mutation detection. RESULTS The final diagnosis was pancreatic ductal adenocarcinoma (PDAC) in all patients (100%). A macroscopic core was obtained in 30 patients (91%). In 3 lesions no cores adequate for histologic analysis were obtained, but cytologic analysis revealed tumoral cells from PDAC. DNA was extracted from 32 of 33 samples (97%), most of which (27/32) carried at least 2 clearly pathogenic mutations in different genes. Detection of K-ras mutation allowed for molecular diagnosis of PDAC in most of the patients (30/32). CONCLUSIONS In our study we demonstrated that proper tissue specimens obtained under EUS guidance allowed DNA sample extraction and subsequent NGS analysis in 97% of cases. These results support the potential role of NGS as a complementary diagnostic test to be implemented in association with standard diagnostic modalities. (Clinical trial registration number: NCT03578939.).
Collapse
Affiliation(s)
- Silvia Carrara
- Department of Gastroenterology, Endoscopic Unit, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
| | - Giulia Soldà
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; Biology Department, Humanitas Clinical and Research Center- IRCCS, Rozzano, Italy
| | - Milena Di Leo
- Department of Gastroenterology, Endoscopic Unit, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
| | - Daoud Rahal
- Department of Pathology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
| | - Clelia Peano
- Genomic Unit, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy; Institute of Genetic and Biomedical Research, UoS Milan, National Research Council, Rozzano, Italy
| | - Michele Giunta
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; Biology Department, Humanitas Clinical and Research Center- IRCCS, Rozzano, Italy
| | - Laura Lamonaca
- Department of Gastroenterology, Endoscopic Unit, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
| | | | - Andrea Anderloni
- Department of Gastroenterology, Endoscopic Unit, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
| | - Alessandro Fugazza
- Department of Gastroenterology, Endoscopic Unit, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
| | - Roberta Maselli
- Department of Gastroenterology, Endoscopic Unit, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
| | - Alberto Malesci
- Department of Gastroenterology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
| | - Luigi Laghi
- Department of Gastroenterology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy; Hereditary Cancer Genetics Clinic, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy; Laboratory of Molecular Gastroenterology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
| | - Alessandro Repici
- Department of Gastroenterology, Endoscopic Unit, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy
| |
Collapse
|
|
38
|
Archibugi L, Ruta V, Panzeri V, Redegalli M, Testoni SGG, Petrone MC, Rossi G, Falconi M, Reni M, Doglioni C, Sette C, Arcidiacono PG, Capurso G. RNA Extraction from Endoscopic Ultrasound-Acquired Tissue of Pancreatic Cancer Is Feasible and Allows Investigation of Molecular Features. Cells 2020; 9:E2561. [PMID: 33266052 PMCID: PMC7761443 DOI: 10.3390/cells9122561] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 11/26/2020] [Accepted: 11/27/2020] [Indexed: 02/07/2023] Open
Abstract
Transcriptome analyses allow the distinguishing of pancreatic ductal adenocarcinoma (PDAC) subtypes, exhibiting different prognoses and chemotherapy responses. However, RNA extraction from pancreatic tissue is cumbersome and has been performed mainly from surgical samples, which are representative of < 20% of cases. The majority of PDAC patients undergo endoscopic ultrasound (EUS)-guided tissue acquisition (EUS-TA), but RNA has been rarely extracted from EUS-TA with scanty results. Herein, we aimed to determine the best conditions for RNA extraction and analysis from PDAC EUS-TA samples in order to carry out molecular analyses. PDAC cases underwent diagnostic EUS-TA, with needles being a 25G fine needle aspiration (FNA) in all patients and then either a 20G lateral core-trap fine needle biopsy (FNB) or a 25G Franseen FNB; the conservation methods were either snap freezing, RNALater or Trizol. RNA concentration and quality (RNA integrity index; RIN) were analyzed and a panel of genes was investigated for tissue contamination and markers of molecular subtype and aggressivity through qRT-PCR. Seventy-four samples from 37 patients were collected. The median RNA concentration was significantly higher in Trizol samples (10.33 ng/uL) compared with snap frozen (0.64 ng/uL; p < 0.0001) and RNALater (0.19 ng/uL; p < 0.0001). The RIN was similar between Trizol (5.15) and snap frozen samples (5.85), while for both methods it was higher compared with RNALater (2.7). Among the needles, no substantial difference was seen in terms of RNA concentration and quality. qRT-PCR analyses revealed that samples from all needles were suitable for the detection of PDAC subtype markers (GATA6 and ZEB1) and splice variants associated with mutational status (GAP17) as well as for the detection of contaminating tissue around PDAC cells. This is the first study that specifically investigates the best methodology for RNA extraction from EUS-TA. A higher amount of good quality RNA is obtainable with conservation in Trizol with a clear superiority of neither FNA nor FNB needles. RNA samples from EUS-TA are suitable for transcriptome analysis including the investigation of molecular subtype and splice variants expression.
Collapse
Affiliation(s)
- Livia Archibugi
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (L.A.); (S.G.G.T.); (M.C.P.); (G.R.); (G.C.)
- Department of Pathology, San Raffaele Scientific Institute IRCCS-Vita Salute San Raffaele University, 20132 Milan, Italy; (M.R.); (M.F.); (C.D.)
| | - Veronica Ruta
- Department of Neuroscience, Section of Human Anatomy, Catholic University of the Sacred Heart, 00168 Rome, Italy; (V.R.); (V.P.); (C.S.)
- Fondazione Policlinico Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Valentina Panzeri
- Department of Neuroscience, Section of Human Anatomy, Catholic University of the Sacred Heart, 00168 Rome, Italy; (V.R.); (V.P.); (C.S.)
- Fondazione Policlinico Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Miriam Redegalli
- Department of Pathology, San Raffaele Scientific Institute IRCCS-Vita Salute San Raffaele University, 20132 Milan, Italy; (M.R.); (M.F.); (C.D.)
- Pathology Department, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
| | - Sabrina Gloria Giulia Testoni
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (L.A.); (S.G.G.T.); (M.C.P.); (G.R.); (G.C.)
- Department of Pathology, San Raffaele Scientific Institute IRCCS-Vita Salute San Raffaele University, 20132 Milan, Italy; (M.R.); (M.F.); (C.D.)
| | - Maria Chiara Petrone
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (L.A.); (S.G.G.T.); (M.C.P.); (G.R.); (G.C.)
- Department of Pathology, San Raffaele Scientific Institute IRCCS-Vita Salute San Raffaele University, 20132 Milan, Italy; (M.R.); (M.F.); (C.D.)
| | - Gemma Rossi
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (L.A.); (S.G.G.T.); (M.C.P.); (G.R.); (G.C.)
| | - Massimo Falconi
- Department of Pathology, San Raffaele Scientific Institute IRCCS-Vita Salute San Raffaele University, 20132 Milan, Italy; (M.R.); (M.F.); (C.D.)
- Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, 20132 Milan, Italy
| | - Michele Reni
- Department of Medical Oncology, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, 20132 Milan, Italy;
| | - Claudio Doglioni
- Department of Pathology, San Raffaele Scientific Institute IRCCS-Vita Salute San Raffaele University, 20132 Milan, Italy; (M.R.); (M.F.); (C.D.)
- Pathology Department, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
| | - Claudio Sette
- Department of Neuroscience, Section of Human Anatomy, Catholic University of the Sacred Heart, 00168 Rome, Italy; (V.R.); (V.P.); (C.S.)
| | - Paolo Giorgio Arcidiacono
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (L.A.); (S.G.G.T.); (M.C.P.); (G.R.); (G.C.)
- Department of Pathology, San Raffaele Scientific Institute IRCCS-Vita Salute San Raffaele University, 20132 Milan, Italy; (M.R.); (M.F.); (C.D.)
| | - Gabriele Capurso
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (L.A.); (S.G.G.T.); (M.C.P.); (G.R.); (G.C.)
- Department of Pathology, San Raffaele Scientific Institute IRCCS-Vita Salute San Raffaele University, 20132 Milan, Italy; (M.R.); (M.F.); (C.D.)
| |
Collapse
|
|
39
|
Song TJ. A New Era of Endoscopic Ultrasound-Guided Tissue Acquisition for Next-Generation Sequencing for Pancreatic Cancer. Gut Liver 2020; 14:279-280. [PMID: 32400145 PMCID: PMC7234890 DOI: 10.5009/gnl20130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Tae Jun Song
- Division of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| |
Collapse
|
|
40
|
Park JK, Lee KH. Present and Future of Endoscopic Ultrasound-Guided Tissue Acquisition in Solid Pancreatic Tumors. Clin Endosc 2019; 52:541-548. [PMID: 31812159 PMCID: PMC6900303 DOI: 10.5946/ce.2019.127] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Accepted: 11/03/2019] [Indexed: 12/16/2022] Open
Abstract
Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is a well-established method for pathological diagnosis of solid pancreatic neoplasm. It can be performed either as EUS-guided fine-needle aspiration (EUS-FNA) or EUS-guided fine-needle biopsy (EUSFNB). The incidence of adverse events related to EUS-TA is less than 1%. The factors that affect the diagnostic accuracy and specimen adequacy include the techniques used, type and size of the needle, competency of endosonographers, presence of cytopathologists/ cytotechnologists, and rapid on-site examination. EUS-TA may contribute to precision medicine through obtaining tissue samples for next-generation sequencing. The current status, several clinical issues for diagnostic yield and adverse events, and future perspectives of EUS-FNA/FNB for diagnosing pancreatic neoplasm have been discussed in this review article.
Collapse
Affiliation(s)
- Jae Keun Park
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soon Chun Hyang University School of Medicine, Bucheon, Korea
| | - Kwang Hyuck Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| |
Collapse
|