CC BY-NC-ND 4.0 · Endosc Int Open 2022; 10(01): E82-E87
DOI: 10.1055/a-1713-3404
Original article

Establishment of organoids using residual samples from saline flushes during endoscopic ultrasound-guided fine-needle aspiration in patients with pancreatic cancer

Kenji Ikezawa
1   Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
,
Tomoya Ekawa
2   Department of Cancer Drug Discovery and Development, Research Center, Osaka International Cancer Institute, Osaka, Japan
,
Shinichiro Hasegawa
3   Department of Surgery, Osaka International Cancer Institute, Osaka, Japan
,
Yugo Kai
1   Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
,
Ryoji Takada
1   Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
,
Takuo Yamai
1   Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
,
Nobuyasu Fukutake
1   Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
,
Hisataka Ogawa
4   Nitto Joint Research Department for Nucleic Acid Medicine, Research Center, Osaka International Cancer Institute, Osaka, Japan
,
Takashi Akazawa
2   Department of Cancer Drug Discovery and Development, Research Center, Osaka International Cancer Institute, Osaka, Japan
,
Yu Mizote
2   Department of Cancer Drug Discovery and Development, Research Center, Osaka International Cancer Institute, Osaka, Japan
,
Kumiko Tatsumi
2   Department of Cancer Drug Discovery and Development, Research Center, Osaka International Cancer Institute, Osaka, Japan
,
Shigenori Nagata
5   Department of Diagnostic Pathology and Cytology, Osaka International Cancer Institute, Osaka, Japan
,
Kei Asukai
3   Department of Surgery, Osaka International Cancer Institute, Osaka, Japan
,
Hidenori Takahashi
3   Department of Surgery, Osaka International Cancer Institute, Osaka, Japan
,
Kazuyoshi Ohkawa
1   Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
,
Hideaki Tahara
2   Department of Cancer Drug Discovery and Development, Research Center, Osaka International Cancer Institute, Osaka, Japan
6   Project Division of Cancer Biomolecular Therapy, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
› Author Affiliations

Abstract

Background and study aims In patients with pancreatic cancer (PC), patient-derived organoid cultures can be useful tools for personalized drug selection and preclinical evaluation of novel therapies. To establish a less invasive method of creating organoids from a patient’s tumor, we examined whether PC organoids can be established using residual samples from saline flushes (RSSFs) during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA).

Methods Five patients with PC who underwent EUS-FNA were enrolled in a prospective study conducted at our institution. RSSFs obtained during EUS-FNA procedures were collected. An organoid culture was considered as established when ≥ 5 passages were successful. Organoid-derived xenografts were created using established organoids.

Results EUS-FNA was performed using a 22- or 25-gauge lancet needle without complications. Patient-derived organoids were successfully established in four patients (80.0 %) with the complete medium and medium for the selection of KRAS mutants. Organoid-derived xenografts were successfully created and histologically similar to EUS-FNA samples.

Conclusions Patient-derived PC organoids were successfully established using EUS-FNA RSSFs, which are produced as a byproduct of standard manipulations, but are usually not used for diagnosis. This method can be applied to all patients with PC, without additional invasive procedures, and can contribute to the development of personalized medicine and molecular research.



Publication History

Received: 15 June 2021

Accepted after revision: 07 October 2021

Article published online:
11 January 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020; 70: 7-30
  • 2 Fukuda J, Ikezawa K, Nakao M. et al. Predictive factors for pancreatic cancer and its early detection using special pancreatic ultrasonography in high-risk individuals. Cancers (Basel) 2021; 13: 1-15
  • 3 Yoshioka T, Shigekawa M, Ikezawa K. et al. Risk factors for pancreatic cancer and the necessity of long-term surveillance in patients with pancreatic cystic lesions. Pancreas 2020; 49: 552-560
  • 4 Franck C, Müller C, Rosania R. et al. Advanced pancreatic ductal adenocarcinoma: Moving forward. Cancers (Basel) 2020; 12: 1955
  • 5 Ikezawa K, Kiyota R, Takada R. et al. Efficacy and safety of modified fluorouracil/leucovorin plus irinotecan and oxaliplatin (mFOLFIRINOX) compared with S-1 as second-line chemotherapy in metastatic pancreatic cancer. JGH Open 2021; 5: 679-685
  • 6 Takahashi H, Ohigashi H, Gotoh K. et al. Preoperative gemcitabine-based chemoradiation therapy for resectable and borderline resectable pancreatic cancer. Ann Surg 2013; 258: 1040-1050
  • 7 Takahashi H, Yamada D, Asukai K. et al. Clinical implications of the serum CA19-9 level in “biological borderline resectability” and “biological downstaging” in the setting of preoperative chemoradiation therapy for pancreatic cancer. Pancreatology 2020; 20: 919-928
  • 8 Takahashi H, Akita H, Tomokuni A. et al. Preoperative gemcitabine-based chemoradiation therapy for borderline resectable pancreatic cancer: impact of venous and arterial involvement status on surgical outcome and pattern of recurrence. Ann Surg 2016; 264: 1091-1097
  • 9 Unno M, Motoi F, Matsuyama Y. et al. Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP-05). J Clin Oncol 2019; 37: 189-189
  • 10 Frappart PO, Hofmann TG. Pancreatic ductal adenocarcinoma (Pdac) organoids: The shining light at the end of the tunnel for drug response prediction and personalized medicine. Cancers (Basel) 2020; 12: 1-18
  • 11 Huang L, Holtzinger A, Jagan I. et al. Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell- and patient-derived tumor organoids. Nat Med 2015; 21: 1364-1371
  • 12 Boj SF, Hwang CIl, Baker LA. et al. Organoid models of human and mouse ductal pancreatic cancer. Cell 2015; 160: 324-338
  • 13 Driehuis E, Van Hoeck A, Moore K. et al. Pancreatic cancer organoids recapitulate disease and allow personalized drug screening. Proc Natl Acad Sci U S A 2019; 116: 26580-26590
  • 14 Tiriac H, Belleau P, Engle DD. et al. Organoid profiling identifies common responders to chemotherapy in pancreatic cancer. Cancer Discov 2018; 8: 1112-1129
  • 15 Tiriac H, Bucobo JC, Tzimas D. et al. Successful creation of pancreatic cancer organoids by means of EUS-guided fine-needle biopsy sampling for personalized cancer treatment. Gastrointest Endosc 2018; 87: 1474-1480
  • 16 Ikezawa K, Shigekawa M, Yamai T. et al. Endoscopic biliary stenting as the risk factor for cholangitis after endoscopic ultrasound in patients with biliary strictures. J Gastroenterol Hepatol 2021; 36: 1263-1266
  • 17 Ikezawa K, Shigekawa M, Sengoku K. et al. Left atrial appendage thrombus detected by transesophageal examination with linear endoscopic ultrasound. Clin Case Rep 2019; 7: 1327-1330
  • 18 Iwashita T, Uemura S, Mita N. et al. Utility of endoscopic ultrasound and endoscopic ultrasound-guided fine-needle aspiration for the diagnosis and management of pancreatic cystic lesions: Differences between the guidelines. Dig Endosc 2020; 32: 251-262
  • 19 Mangiavillano B, Sosa-Valencia L, Deprez P. et al. Tissue acquisition and pancreatic masses: Which needle and which acquisition technique should be used?. Endosc Int Open 2020; 8: E1315-E1320
  • 20 Yamabe A, Irisawa A, Bhutani MS. et al. Efforts to improve the diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration for pancreatic tumors. Endosc Ultrasound 2016; 5: 225-232
  • 21 Matsumoto K, Kato H, Nouso K. et al. Evaluation of local recurrence of pancreatic cancer by KRAS mutation analysis using washes from endoscopic ultrasound-guided fine-needle aspiration. Dig Dis Sci 2020; 65: 2907-2913
  • 22 Kai Y, Ikezawa K, Takada R. et al. Success rate of microsatellite instability examination and complete response with pembrolizumab in biliary tract cancer. JGH Open 2021; 5: 712-716
  • 23 Yane K, Kuwatani M, Yoshida M. et al. Non-negligible rate of needle tract seeding after endoscopic ultrasound-guided fine-needle aspiration for patients undergoing distal pancreatectomy for pancreatic cancer. Dig Endosc 2020; 32: 801-811
  • 24 Kanno A, Yasuda I, Irisawa A. et al. Adverse events of endoscopic ultrasound-guided fine-needle aspiration for histologic diagnosis in Japanese tertiary centers: Multicenter retrospective study. Dig Endosc 2020; DOI: 10.1111/den.13912.
  • 25 Brierley J, Gospodarowicz M, Wittekind C. TNM classification of malignant tumours. 8th ed. Hoboken (New Jersey), US: Wiley-Blackwell; 2017
  • 26 Seino T, Kawasaki S, Shimokawa M. et al. Human pancreatic tumor organoids reveal loss of stem cell niche factor dependence during disease progression. Cell Stem Cell 2018; 22: 454-467.e6
  • 27 Yin L, Pu N, Thompson E. et al. Improved assessment of response status in patients with pancreatic cancer treated with neoadjuvant therapy using somatic mutations and liquid biopsy analysis. Clin Cancer Res 2021; 27: 740-748
  • 28 Miyasaka Y, Ohtsuka T, Kimura R. et al. Neoadjuvant chemotherapy with gemcitabine plus nab-paclitaxel for borderline resectable pancreatic cancer potentially improves survival and facilitates surgery. Ann Surg Oncol 2019; 26: 1528-1534
  • 29 Yoo C, Hwang I, Song TJ. et al. FOLFIRINOX in borderline resectable and locally advanced unresectable pancreatic adenocarcinoma. Ther Adv Med Oncol 2020; DOI: 10.1177/1758835920953294.
  • 30 Pishvaian MJ, Blais EM, Brody JR. et al. Overall survival in patients with pancreatic cancer receiving matched therapies following molecular profiling: a retrospective analysis of the Know Your Tumor registry trial. Lancet Oncol 2020; 21: 508-518
  • 31 Takada R, Ikezawa K, Kiyota R. et al. Microsatellite instability status of pancreatic cancer and experience with pembrolizumab treatment. Suizo 2021; 36: 120-127
  • 32 Marabelle A, Le DT, Ascierto PA. et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/ mismatch repair–deficient cancer: Results from the phase II KEYNOTE-158 study. J Clin Oncol 2020; 38: 1-10
  • 33 Park W, Chen J, Chou JF. et al. Genomic methods identify homologous recombination deficiency in pancreas adenocarcinoma and optimize treatment selection. Clin Cancer Res 2020; 26: 3239-3247
  • 34 Imaoka H, Sasaki M, Hashimoto Y. et al. Impact of endoscopic ultrasound-guided tissue acquisition on decision-making in precision medicine for pancreatic cancer: beyond diagnosis. Diagnostics 2021; 11: 1195