Endoscopy 2019; 51(09): 825-835
DOI: 10.1055/a-0732-5356
Original article
© Georg Thieme Verlag KG Stuttgart · New York

Needle-based confocal laser endomicroscopy of pancreatic cystic lesions: a prospective multicenter validation study in patients with definite diagnosis

Bertrand Napoleon
1   Département de Gastroentérologie, Hôpital Privé Jean Mermoz, Ramsay GDS, Lyon, France
,
Maxime Palazzo
2   Département d’Endoscopie Digestive, Hôpital Beaujon, Clichy, France
,
Anne-Isabelle Lemaistre
3   Département de Biopathologie, Eurofins Biomnis, Lyon, France
,
Fabrice Caillol
4   Unité d’Échoendoscopie et d’Endoscopie d’Oncologie Digestive, Institut Paoli Calmettes, Marseille, France
,
Laurent Palazzo
5   Clinique du Trocadéro, Paris, France
,
Alain Aubert
2   Département d’Endoscopie Digestive, Hôpital Beaujon, Clichy, France
,
Louis Buscail
6   Service d’Hépatogastroenterologie, Hôpital Rangueil, Toulouse, France
,
Frédérique Maire
2   Département d’Endoscopie Digestive, Hôpital Beaujon, Clichy, France
,
Blandine Mialhe Morellon
7   Cabinet d’Anatomo-cyto-pathologie, Technipath, Limonest, France
,
Bertrand Pujol
1   Département de Gastroentérologie, Hôpital Privé Jean Mermoz, Ramsay GDS, Lyon, France
,
Marc Giovannini
4   Unité d’Échoendoscopie et d’Endoscopie d’Oncologie Digestive, Institut Paoli Calmettes, Marseille, France
› Institutsangaben
Weitere Informationen

Publikationsverlauf

submitted 08. März 2018

accepted after revision 31. Juli 2018

Publikationsdatum:
22. Oktober 2018 (online)

Abstract

Background Needle-based confocal laser endomicroscopy (nCLE) enables observation of the inner wall of pancreatic cystic lesions (PCLs) during an endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). This study prospectively evaluated the diagnostic performance of nCLE for large, single, noncommunicating PCLs using surgical histopathology or EUS-FNA cytohistopathology as a reference diagnosis.

Methods From April 2013 to March 2016, consecutive patients referred for EUS-FNA of indeterminate PCLs without evidence of malignancy or chronic pancreatitis were prospectively enrolled at five centers. EUS-FNA and nCLE were performed and cystic fluid was aspirated for cytohistopathological and carcinoembryonic antigen (CEA) analysis. The diagnostic performance of nCLE was assessed against the reference standard and compared with that of EUS and CEA. This study was registered on ClinicalTrials.gov (NCT01563133).

Results 206 patients underwent nCLE and 78 PCLs (mean size 40 mm, range 20 – 110 mm) had reference diagnoses (53 premalignant and 25 benign PCLs). Post-procedure pancreatitis occurred in 1.3 % of the patients. nCLE was conclusive in 71 of the 78 cases (91 %). The sensitivies and specifities of nCLE for the diagnosis of serous cystadenoma, mucinous PCL, and premalignant PCL were all ≥ 0.95 (with 95 % confidence interval from 0.85 to 1.0). The AUROC was significantly larger for nCLE than for CEA or EUS.

Conclusions nCLE had excellent diagnostic performance that surpassed that of CEA and EUS for the diagnosis of large, single, noncommunicating PCLs. The nCLE procedure should be considered in patients with indeterminate PCLs to ensure a more specific diagnosis.

Supplemental Fig. e3, e4, Supplemental Table e2, e5

 
  • References

  • 1 Laffan TA, Horton KM, Klein AP. Prevalence of unsuspected pancreatic cysts on MDCT. Am J Roentgenol 2008; 191: 802-807
  • 2 de Jong K, Nio CY, Hermans JJ. High prevalence of pancreatic cysts detected by screening magnetic resonance imaging examinations. Clin Gastroenterol Hepatol 2010; 8: 806-811
  • 3 Chiang AL. Clinical approach to incidental pancreatic cysts. World J Gastroenterol 2016; 22: 1236
  • 4 Tanaka M, Fernández-del CastilloC, Adsay V. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology 2012; 12: 183-197
  • 5 Brugge WR, Lewandrowski K, Lee-Lewandrowski E. Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology 2004; 126: 1330-1336
  • 6 Thosani N, Thosani S, Qiao W. Role of EUS-FNA-based cytology in the diagnosis of mucinous pancreatic cystic lesions: a systematic review and meta-analysis. Dig Dis Sci 2010; 55: 2756-2766
  • 7 Thornton GD, McPhail MJW, Nayagam S. Endoscopic ultrasound guided fine needle aspiration for the diagnosis of pancreatic cystic neoplasms: a meta-analysis. Pancreatology 2013; 13: 48-57
  • 8 van der Waaij LA, van Dullemen HM, Porte RJ. Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis. Gastrointest Endosc 2005; 62: 383-389
  • 9 Bhutani MS. Role of endoscopic ultrasonography in the diagnosis and treatment of cystic tumors of the pancreas. JOP 2004; 5: 266-272
  • 10 Belsley NA, Pitman MB, Lauwers GY. Serous cystadenoma of the pancreas: limitations and pitfalls of endoscopic ultrasound-guided fine-needle aspiration biopsy. Cancer 2008; 114: 102-110
  • 11 Park WG-U, Mascarenhas R, Palaez-Luna M. Diagnostic performance of cyst fluid carcinoembryonic antigen and amylase in histologically confirmed pancreatic cysts. Pancreas 2011; 40: 42-45
  • 12 Valsangkar NP, Morales-Oyarvide V, Thayer SP. 851 resected cystic tumors of the pancreas: a 33-year experience at the Massachusetts General Hospital. Surgery 2012; 152: S4-S12
  • 13 Gaujoux S, Brennan MF, Gonen M. Cystic lesions of the pancreas: changes in the presentation and management of 1,424 patients at a single institution over a 15-year time period. J Am Coll Surg 2011; 212: 590-600
  • 14 Fugazza A, Gaiani F, Carra MC. Confocal laser endomicroscopy in gastrointestinal and pancreatobiliary diseases: a systematic review and meta-analysis. Biomed Res Int 2016; 2016: 1-31
  • 15 Becker V, Wallace MB, Fockens P. Needle-based confocal endomicroscopy for in vivo histology of intra-abdominal organs: first results in a porcine model (with video). Gastrointest Endosc 2010; 71: 1260-1266
  • 16 Konda VJA, Aslanian HR, Wallace MB. First assessment of needle-based confocal laser endomicroscopy during EUS-FNA procedures of the pancreas (with videos). Gastrointest Endosc 2011; 74: 1049-1060
  • 17 Konda V, Meining A, Jamil L. A pilot study of in vivo identification of pancreatic cystic neoplasms with needle-based confocal laser endomicroscopy under endosonographic guidance. Endoscopy 2013; 45: 1006-1013
  • 18 Napoléon B, Lemaistre A-I, Pujol B. A novel approach to the diagnosis of pancreatic serous cystadenoma: needle-based confocal laser endomicroscopy. Endoscopy 2014; 47: 26-32
  • 19 Napoleon B, Lemaistre A-I, Pujol B. 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 2016; 30: 2603-2612
  • 20 Krishna S, Swanson B, Hart P. Validation of diagnostic characteristics of needle based confocal laser endomicroscopy in differentiation of pancreatic cystic lesions. Endosc Int Open 2016; 4: E1124-E1135
  • 21 Krishna SG, Brugge WR, Dewitt JM. Needle-based confocal laser endomicroscopy for the diagnosis of pancreatic cystic lesions: an international external interobserver and intraobserver study (with videos). Gastrointest Endosc 2017; 86: 644-654
  • 22 Nakai Y, Iwashita T, Park DH. Diagnosis of pancreatic cysts: EUS-guided, through-the-needle confocal laser-induced endomicroscopy and cystoscopy trial: DETECT study. Gastrointest Endosc 2015; 81: 1204-1214
  • 23 Karia K, Waxman I, Konda VJ. Needle-based confocal endomicroscopy for pancreatic cysts: the current agreement in interpretation. Gastrointest Endosc 2016; 83: 924-927
  • 24 Kadayifci A, Atar M, Basar O. Needle-based confocal laser endomicroscopy for evaluation of cystic neoplasms of the pancreas. Dig Dis Sci 2017; 62: 1346-1353
  • 25 Kadayifci A, Atar M, Yang M. Imaging of pancreatic cystic lesions with confocal laser endomicroscopy: an ex vivo pilot study. Surg Endosc 2017; 31: 5119-5126
  • 26 Becker V, von Delius S, Bajbouj M. Intravenous application of fluorescein for confocal laser scanning microscopy: evaluation of contrast dynamics and image quality with increasing injection-to-imaging time. Gastrointest Endosc 2008; 68: 319-323
  • 27 Soyer OM, Baran B, Ormeci AC. Role of biochemistry and cytological analysis of cyst fluid for the differential diagnosis of pancreatic cysts: a retrospective cohort study. Medicine (Baltimore) 2017; 96: e5513
  • 28 DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988; 44: 837-845
  • 29 de Jong K, Poley J-W, van Hooft J. Endoscopic ultrasound-guided fine-needle aspiration of pancreatic cystic lesions provides inadequate material for cytology and laboratory analysis: initial results from a prospective study. Endoscopy 2011; 43: 585-590
  • 30 Jais B, Rebours V, Malleo G. et al. Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas). Gut 2016; 65: 305-312
  • 31 Le PenC, Palazzo L, Napoléon B. A health economic evaluation of needle-based confocal laser endomicroscopy for the diagnosis of pancreatic cysts. Endosc Int Open 2017; 5: E987-E995
  • 32 Kung JS, Lopez OA, McCoy EE. Fluid genetic analyses predict the biological behavior of pancreatic cysts: three-year experience. JOP 2014; 15: 413-540
  • 33 Springer S, Wang Y, Dal MolinM. A combination of molecular markers and clinical features improve the classification of pancreatic cysts. Gastroenterology 2015; 149: 1501-1510
  • 34 Bick B, Enders F, Levy M. The string sign for diagnosis of mucinous pancreatic cysts. Endoscopy 2015; 47: 626-631