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In vivo characterization of pancreatic cystic lesions by needle-based confocal laser endomicroscopy (nCLE): proposition of a comprehensive nCLE classification confirmed by an external retrospective evaluation

Abstract

Background and aims

The differential diagnosis of solitary pancreatic cystic lesions is sometimes difficult. Needle-based confocal laser endomicroscopy (nCLE) performed during endoscopic ultrasound–fine-needle aspiration (EUS-FNA) enables real-time imaging of the internal structure of such cysts. Criteria have already been described for serous cystadenoma and intraductal papillary mucinous neoplasm (IPMN). The aims of the study were to determine new nCLE criteria for the diagnosis of pancreatic cystic lesions, to propose a comprehensive nCLE classification for the characterization of those lesions, and to carry out a first external retrospective validation .

Methods

Thirty-three patients with a lone pancreatic cystic lesion were included (CONTACT 1 study). EUS-FNA was combined with nCLE. Diagnosis was based on either pathology result (Group 1, n = 20) or an adjudication committee consensus (Group 2, n = 13). Six investigators, unblinded, studied cases from Group 1 and identified nCLE criteria for mucinous cystic neoplasm (MCN), pseudocyst (PC), and cystic neuroendocrine neoplasm (NEN). Four external reviewers assessed, blinded, the yield and interobserver agreement for the newly identified (MCN, PC) and previously described (IPMN, SC) criteria in a subset of 31 cases.

Results

New nCLE criteria were described for MCN (thick gray line), PC (field of bright particles), and cystic NEN (black neoplastic cells clusters with white fibrous areas). These criteria correlated with the histological features of the corresponding lesions. In the retrospective validation, a conclusive nCLE result was obtained for 74 % of the cases (87 % “true” and 13 % “false” with respect to the final diagnosis). On this limited case series, the nCLE criteria showed a trend for high diagnostic specificity (>90 % for mucinous cysts, 100 % for non-mucinous cysts).

Conclusions

Based on this newly completed atlas of interpretation criteria, nCLE could facilitate the diagnosis of pancreatic cystic lesion types.

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References

  1. 1.

    Gardner TB, Glass LM, Smith KD, Ripple GH, Barth RJ, Klibansky DA, Colacchio TA, Tsapakos MJ, Suriawinata AA, Tsongalis GJ, Pipas JM, Gordon SR (2013) Pancreatic cyst prevalence and the risk of mucin-producing adenocarcinoma in US adults. Am J Gastroenterol 108:1546–1550

  2. 2.

    Brugge WR, Lewandrowski K, Lee-Lewandrowski E, Centeno BA, Szydlo T, Regan S, del Castillo CF, Warshaw AL (2004) Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology 126:1330–1336

  3. 3.

    Khalid A, Brugge W (2007) ACG practice guidelines for the diagnosis and management of neoplastic pancreatic cysts. Am J Gastroenterol 102:2339–2349

  4. 4.

    Thosani N, Thosani S, Qiao W, Fleming JB, Bhutani MS, Guha S (2010) Role of EUS-FNA-based cytology in the diagnosis of mucinous pancreatic cystic lesions: a systematic review and meta-analysis. Dig Dis Sci 55:2756–2766

  5. 5.

    Thornton GD, McPhail MJ, Nayagam S, Hewitt MJ, Vlavianos P, Monahan KJ (2013) Endoscopic ultrasound guided fine needle aspiration for the diagnosis of pancreatic cystic neoplasms: a meta-analysis. Pancreatology 13:48–57

  6. 6.

    Bhutani MS (2004) Role of endoscopic ultrasonography in the diagnosis and treatment of cystic tumors of the pancreas. JOP 5:266–272

  7. 7.

    Belsley NA, Pitman MB, Lauwers GY, Brugge WR, Deshpande V (2008) Serous cystadenoma of the pancreas: limitations and pitfalls of endoscopic ultrasound-guided fine-needle aspiration biopsy. Cancer 114:102–110

  8. 8.

    Van der Waaij LA, van Dullemen HM, Porte RJ (2005) Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis. Gastrointest Endosc 62:383–389

  9. 9.

    Park WG, Mascarenhas R, Palaez-Luna M, Smyrk TC, O’Kane D, Clain JE, Levy MJ, Pearson RK, Petersen BT, Topazian MD, Vege SS, Chari ST (2011) Diagnostic performance of cyst fluid carcinoembryonic antigen and amylase in histologically confirmed pancreatic cysts. Pancreas 40:42–45

  10. 10.

    Huang ES, Turner BG, Fernandez-Del-Castillo C, Brugge WR, Hur C (2010) Pancreatic cystic lesions: clinical predictors of malignancy in patients undergoing surgery. Aliment Pharmacol Ther 31:285–294

  11. 11.

    Jais B, Rebours V, Malleo G, Salvia R, Fontana M, Maggino L, Bassi C, Manfredi R, Moran R, Lennon AM, Zaheer A, Wolfgang C, Hruban R, Marchegiani G, Fernández Del Castillo C, Brugge W, Ha Y, Kim MH, Oh D, Hirai I, Kimura W, Jang JY, Kim SW, Jung W, Kang H, Song SY, Kang CM, Lee WJ, Crippa S, Falconi M, Gomatos I, Neoptelomos J, Milanetto AC, Sperti C, Ricci C, Casadei R, Bissolati M, Balzano G, Frigerio I, Girelli R, Delhaye M, Bernier B, Wang H, Jang KT, Song DH, Huggett MT, Oppong KW, Pererva L, Kopchak KV, Del Chiaro M, Segersvard R, Lee LS, Conwell D, Osvaldt A, Campos V, Aguero Garcete G, Napoleon B, Matsumoto I, Shinzeki M, Bolado F, Urman Fernandez JM, Keane MG, Pereira SP, Araujo Acuna I, Vaquero EC, Angiolini MR, Zerbi A, Tang J, Leong RW, Faccinetto A, Morana G, Petrone MC, Arcidiacono PG, Moon JH, Choi HJ, Gill RS, Pavey D, Ouaïssi M, Sastre B, Spandre M, De Angelis CG, Rios-Vives MA, Concepcion-Martin M, Ikeura T, Okazaki K, Frulloni L,Messina O, Lévy P (2015) Pancreatic serous cystadenoma related mortality is nil. Results of a multinational study under the auspices of the International Association of Pancreatology and the European Pancreatic Club. Gut, doi:10.1136/gutjnl-2015-309638, 4 June 2015

  12. 12.

    Mennone A, Nathanson MH (2011) Needle-based confocal laser endomicroscopy to assess liver histology in vivo. Gastrointest Endosc 73:338–344

  13. 13.

    Becker V, Wallace MB, Fockens P, von Delius S, Woodward TA, Raimondo M, Voermans RP, Meining A (2010) Needle-based confocal endomicroscopy for in vivo histology of intra-abdominal organs: first results in a porcine model (with videos). Gastrointest Endosc 71:1260–1266

  14. 14.

    Konda VJ, Aslanian HR, Wallace MB, Siddiqui UD, Hart J, Waxman I (2011) First assessment of needle-based confocal laser endomicroscopy during EUS-FNA procedures of the pancreas (with videos). Gastrointest Endosc 74:1049–1060

  15. 15.

    Konda VJ, Meining A, Jamil LH, Giovannini M, Hwang JH, Wallace MB, Chang KJ, Siddiqui UD, Hart J, Lo SK, Saunders MD, Aslanian HR, Wroblewski K, Waxman I (2013) A pilot study of in vivo identification of pancreatic cystic neoplasms with needle-based confocal laser endomicroscopy under endosonographic guidance. Endoscopy 45:1006–1013

  16. 16.

    Napoleon B, Lemaistre AI, Pujol B, Caillol F, Lucidarme D, Bourdariat R, Morellon-Mialhe B, Fumex F, Lefort C, Lepilliez V, Palazzo L, Monges G, Filoche B, Giovannini M (2015) A novel approach to the diagnosis of pancreatic serous cystadenoma: needle-based confocal laser endomicroscopy. Endoscopy 47:26–32

  17. 17.

    Napoleon B, Lemaistre AI, Pujol B, Caillol F, Mialhe-Morellon B, Giovannini M (2014) In vivo characterization of pancreatic cystic tumors by needle-based confocal laser endomicroscopy (nCLE). Proposition of a comprehensive classification. Gastrointest Endosc 79:AB434–AB435

  18. 18.

    Spinelli KS, Fromwiller TE, Daniel RA, Kiely JM, Nakeeb A, Komorowski RA, Wilson SD, Pitt HA (2004) Cystic pancreatic neoplasms: observe or operate. Ann Surg 239:651–657

  19. 19.

    Walsh RM, Vogt DP, Henderson JM, Zuccaro G, Vargo J, Dumot J, Herts B, Biscotti CV, Brown N (2005) Natural history of indeterminate pancreatic cysts. Surgery 138:665–670

  20. 20.

    Allen PJ, Jaques DP, D’Angelica M, Bowne WB, Conlon KC, Brennan MF (2003) Cystic lesions of the pancreas: selection criteria for operative and nonoperative management in 209 patients. J Gastrointest Surg 7:970–977

  21. 21.

    Hawes RH, Clancy J, Hasan MK (2012) Endoscopic ultrasound-guided fine needle aspiration in cystic pancreatic lesions. Clin Endosc 45:128–131

  22. 22.

    Diener MK, Knaebel HP, Heukaufer C, Antes G, Büchler MW, Seiler CM (2007) A systematic review and meta-analysis of pylorus-preserving versus classical pancreaticoduodenectomy for surgical treatment of periampullary and pancreatic carcinoma. Ann Surg 245:187–200

  23. 23.

    Malleo G, Bassi C, Rossini R, Manfredi R, Butturini G, Massignani M, Paini M, Pederzoli P, Salvia R (2012) Growth pattern of serous cystic neoplasms of the pancreas: observational study with long-term magnetic resonance surveillance and recommendations for treatment. Gut 61:746–751

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Acknowledgments

We would like to thank all procedural nurses and staff for their assistance during procedures. We would like to thank Cécile Redon and Claire Burucoa from Mauna Kea Technologies for additional logistical support during the trial.

Funding

This study has been funded by Mauna Kea Technologies.

Author information

Correspondence to Bertrand Napoleon.

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Disclosures

Dr. Napoleon reports non-financial support from Mauna Kea Technologies, Grants from Mauna Kea Technologies, personal fees from Mauna Kea Technologies, during the conduct of the study; personal fees from Mauna Kea Technologies, outside the submitted work. Dr. Lemaistre reports personal fees from Mauna Kea Technologies, during the conduct of the study; personal fees from Mauna Kea Technologies, outside the submitted work. Dr. Pujol reports non-financial support from Mauna Kea Technologies, Grants from Mauna Kea Technologies, personal fees from Mauna Kea Technologies, during the conduct of the study. Dr. Caillol reports non-financial support from Mauna Kea Technologies, Grants from Mauna Kea Technologies, during the conduct of the study. Dr. Lucidarme reports non-financial support from Mauna Kea Technologies, Grants from Mauna Kea Technologies, during the conduct of the study. Drs. Bourdariat, Fumex, Lefort, Lepilliez, Monges, Morellon-Mialhe, and Poizat have nothing to disclose. Dr. Palazzo reports non-financial support from Mauna Kea Technologies, during the conduct of the study. Dr. Giovannini reports non-financial support from Mauna Kea Technologies, Grants from Mauna Kea Technologies, during the conduct of the study.

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Napoleon, B., Lemaistre, A., Pujol, B. et al. In vivo characterization of pancreatic cystic lesions by needle-based confocal laser endomicroscopy (nCLE): proposition of a comprehensive nCLE classification confirmed by an external retrospective evaluation. Surg Endosc 30, 2603–2612 (2016) doi:10.1007/s00464-015-4510-5

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Keywords

  • EUS-FNA
  • Pancreatic cysts
  • Needle-based confocal laser endomicroscopy