Advertisement

Clinical Journal of Gastroenterology

, Volume 12, Issue 2, pp 93–101 | Cite as

Current indications and yield of endoscopic ultrasound and ancillary techniques in pancreatic cystic neoplasms

  • Federico SalomEmail author
  • Frédéric Prat
Clinical Review
  • 156 Downloads

Abstract

An increase in the diagnosis of pancreatic cystic neoplasm has been described lately. Surgical treatment or surveillance is advised depending on the type of lesion diagnosed. The most accurate diagnostic approach is needed to make the best therapeutic decision. Endoscopic ultrasound is a very valuable tool in the evaluation of pancreatic cystic neoplasm. It generates high-quality images and allows the possibility of sampling the cystic fluid for cytology, microbiological and molecular evaluation. Even with this evaluation, the sensitivity of this approach is not always adequate. New technological resources have been developed to try to improve the diagnostic accuracy of pancreatic cystic neoplasms. The two most promising techniques are needle-based confocal laser endomicroscopy and contrast-enhanced harmonic endoscopic ultrasound. Needle-based confocal laser endomicroscopy allows a microscopic evaluation of mucosal glands and vascular pattern, to differentiate mucinous from non-mucinous lesions. Contrast-enhanced harmonic endoscopic ultrasound is used for the vascular evaluation of the microcirculation of the cyst wall and mural nodule, mainly to make the difference between malignant nodules and mucus plugs. A combination of these different diagnostic techniques can improve the diagnostic accuracy of pancreatic cystic neoplasms to offer the adequate therapeutic decision.

Keywords

Pancreatic cystic neoplasm Endoscopic ultrasound Fine-needle aspiration Endomicroscopy Contrast-enhanced harmonic endoscopic ultrasound 

Notes

Acknowledgements

The authors disclose no financial relationships or conflict of interest relevant to this publication.

Funding

None declared.

Compliance with ethical standards

Conflict of interest

Federico Salom and Frédéric Prat declare that they have no conflict of interest.

Human/animal rights

All procedures followed have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed consent

The study did not involve human subjects so no informed consent was obtained.

References

  1. 1.
    Laffan TA, Horton KM, Klein AP, et al. Prevalence of unsuspected pancreatic cysts on MDCT. AJR. 2008;191:802–7.CrossRefGoogle Scholar
  2. 2.
    Kimura W, Nagai H, Kuroda A, et al. Analysis of small cystic lesions of the pancreas. Int J Pancreatol. 1995;18:197–206.Google Scholar
  3. 3.
    Scheiman JM, Hwang JH, Moayyedi P. American gastroenterological association technical review on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology. 2015;148:824–48.CrossRefGoogle Scholar
  4. 4.
    Vege SS, Ziring B, Jain R, et al. American gastroenterological association institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology. 2015;148:819–22.CrossRefGoogle Scholar
  5. 5.
    Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.CrossRefGoogle Scholar
  6. 6.
    Khurana B, Mortele KJ, Glickman J, et al. Macrocystic serous adenoma of the pancreas: radiologic-pathologic correlation. AJR. 2003;181:119–23.CrossRefGoogle Scholar
  7. 7.
    Terris B, Fukishima N, Hruban RH. Serous neoplasms of the pancreas. World Health Organization classification of tumors of the digestive system. 4th ed. Lyon: IARC; 2010. pp. 296–9.Google Scholar
  8. 8.
    Yoon WJ, Lee JK, Lee KH, et al. Cystic neoplasms of the exocrine pancreas: an update of a nationwide survey in Korea. Pancreas. 2008;37:254–8.CrossRefGoogle Scholar
  9. 9.
    Sakorafas GH, Smyrniotis V, Reid-Lombardo KM, et al. Primary pancreatic cystic neoplasms revisited. Part I. Serous cystic neoplasms. Surg Oncol. 2011;20:e84 –92.CrossRefGoogle Scholar
  10. 10.
    Prasad HL, Ballai R, Upadhyay V, et al. Serous microcystic adenoma to adenocarcinoma of the pancreas—a case report. Indian J Surg Oncol. 2015;6:82–5.CrossRefGoogle Scholar
  11. 11.
    Petrone MC, Arcidiacono PG. Role of endosocopic ultrasound in the diagnosis of cystic tumours of the pancreas. Dig Liver Dis. 2008;40:847–53.CrossRefGoogle Scholar
  12. 12.
    Mohr VH, Vortmeyer AO, Zhuang Z, et al. Histopathology and molecular genetics of multiple cysts and microcystic (serous) cystadenomas of the pancreas in Von Hipple–Lindau patients. Am J Pathol. 2000;157:1615–21.CrossRefGoogle Scholar
  13. 13.
    Lonser RR, Glen GM, Walther M, et al. Von Hippel–Lindau disease. Lancet. 2003;361:2059–67.CrossRefGoogle Scholar
  14. 14.
    Zamboni G, Fukushima N, Hruban RH. Mucinous cystic neoplasms of the pancreas. World Health Organization classification of tumors of the digestive system. 4th ed. Lyon: IARC; 2010. pp. 300–3.Google Scholar
  15. 15.
    Brugge WR, Lewandrowski K, Lee-Lewandrowski E, et al. Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology. 2004;126:1330–6.CrossRefGoogle Scholar
  16. 16.
    Fasanella KE, McGrath K. Cystic lesions and intraductal neoplasms of the pancreas. Best Pract Res Clin Gastroenterol. 2009;23:35–48.CrossRefGoogle Scholar
  17. 17.
    Nilsson L, Keane M, Shamali A, et al. Nature and management of pancreatic mucinous cystic neoplasm (MCN): systematic review of the literature. Pancreatology. 2016;16:1028–36.CrossRefGoogle Scholar
  18. 18.
    Crippa S, Salvia R, Warshaw AL, et al. Mucinous cystic neoplasm of the pancreas is not an aggressive entity: lessons from 163 resected patients. Ann Surg. 2008;247:571–9.CrossRefGoogle Scholar
  19. 19.
    Hruban RH, Takaori K, Klimstra DS, et al. An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol. 2004;28:977–87.CrossRefGoogle Scholar
  20. 20.
    Fernández-del Castillo C, Adsay NV. Intraductal papillary mucinous neooplasms of the pancreas. Gastroenterology. 2010;139:708 – 13.CrossRefGoogle Scholar
  21. 21.
    Adsay NV, Fukushima N, Furukawa T. Intraductal neoplasms of the pancreas. In: World Health Organization classification of tumors of the digestive system. 4th ed. Lyon: IARC; 2010. pp. 304–13.Google Scholar
  22. 22.
    Crippa S, Fernández-Del Castillo C, Salvia R, et al. Mucin-producing neoplasms of the pancreas: an analysis of distinguishing clinical and epidemiologic characteristics. Clin Gastroenterol Hepatol. 2010;8:213–9.CrossRefGoogle Scholar
  23. 23.
    Kloppel G, Hruban RH, Klimstra D. Solid-pseudopapillary neoplasm of the pancreas. In: World Health Organization classification of tumors of the digestive system. 4th ed. Lyon: IARC; 2010. pp. 327–30.Google Scholar
  24. 24.
    Papavramidis T, Papavramidis S. Solid pseudopapillary tumors of the pancreas: review of 718 patients reported in English literature. J Am Coll Surg. 2005;200:965–72.CrossRefGoogle Scholar
  25. 25.
    Bordeianou L, Vagefi PA, Sahani DV, et al. Cystic pancreatic endocrine neoplasms: a distinct tumor type? J Am Coll Surg. 2008;206:1154–8.CrossRefGoogle Scholar
  26. 26.
    Boninsegna L, Partelli S, D’Innocenzio MM, et al. Pancreatic cystic endocrine tumors: a different morphological entity associated with a less aggressive behavior. Neuroendocrinology. 2010;92:246 – 51.CrossRefGoogle Scholar
  27. 27.
    Gaujoux S, Tang L, Klimstra D, et al. The outcome of resected cystic pancreatic endocrine neoplasms: a case-matched analysis. Surgery. 2012;151:518 – 25.CrossRefGoogle Scholar
  28. 28.
    Koh YX, Chok AY, Zheng HL, et al. A systematic review and meta-analysis of the clinicopathologic characteristics of cystic versus solid pancreatic neuroendocrine neoplasms. Surgery. 2014;156:83–96.CrossRefGoogle Scholar
  29. 29.
    Partelli S, Cirocchi R, Crippa S, et al. Systematic review of active surveillance versus surgical management of asymptomatic small non-functioning pancreatic neuroendocrine neoplasms. Br J Surg. 2017;104:34–41.CrossRefGoogle Scholar
  30. 30.
    Cloyd JM, Kopecky KE, Norton JA, et al. Neuroendocrine tumors of the pancreas: degree of cystic component predicts prognosis. Surgery. 2016;160:708–13.CrossRefGoogle Scholar
  31. 31.
    Hurtado-Pardo L, Cienfuegos A, Ruiz-Canela J. M, et al. Cystic pancreatic neuroendocrine tumors (cPNETs): a systematic review and meta-analysis of case series. Rev Esp Enferm Dig. 2017;109:778–87.CrossRefGoogle Scholar
  32. 32.
    Tseng JF, Warshaw AL, Sahani DV, et al. Serous cystadenoma of the pancreas: tumor growth rates and recommendations for treatment. Ann Surg. 2005;242:413–9.Google Scholar
  33. 33.
    Le Baleur Y, Couvelard A, Vullierme MP, et al. Mucinous cystic neoplasms of the pancreas: definition of preoperative imaging criteria for high-risk lesions. Pancreatology. 2011;11:495–9.CrossRefGoogle Scholar
  34. 34.
    Tanaka M, Chari S, Adsay V, et al. International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology. 2006;6:17–32.CrossRefGoogle Scholar
  35. 35.
    Tanaka M, Fernández-del Castillo C, Adsay V, et al. International consensus guidelines 2012 for management of IPMN and MCN of the pancreas. Pancreatology. 2012;12:183–97.CrossRefGoogle Scholar
  36. 36.
    Balci NC, Semelka RC. Radiologic features of cystic, endocrine and other pancreatic neoplasms. Euro J Radiol. 2001;38:113–9.CrossRefGoogle Scholar
  37. 37.
    Kim JH, Eun HW, Park HJ, et al. Diagnostic performance of MRI and EUS in the differentiation of benign from malignant pancreatic cyst and cyst communication with the main duct. Eur J Radiol. 2012;81:2927–35.CrossRefGoogle Scholar
  38. 38.
    Zhang XM, Mitchell DG, Dohke M, et al. Pancreatic cysts: depiction on single-shot fast spin-echo MR images. Radiology. 2002;223:547–53.CrossRefGoogle Scholar
  39. 39.
    Sainani NI, Saokar A, Deshpande V, et al. Comparative performance of MDCT and MRI with MR cholangiopancreatography in characterizing small pancreatic cysts. AJR AM J Roentgenol. 2009;193:722–31.CrossRefGoogle Scholar
  40. 40.
    Lee HJ, Kim MJ, Choi JY, et al. Relative accuracy of CT and MRI in the differentiation of benign from malignant pancreatic cystic lesions. Clin Radiol. 2011;66:315–21.CrossRefGoogle Scholar
  41. 41.
    Jang DK, Song BJ, Ryu JK, et al. Preoperative diagnosis of pancreatic cystic lesions: the accuracy of endoscopic ultrasound and cross-sectional imaging. Pancreas. 2015;44:1329–33.CrossRefGoogle Scholar
  42. 42.
    Gerke H, Jaffe TA, Mitchell RM, et al. Endoscopic ultrasound and computer tomography are inaccurate methods of classifying cystic pancreatic lesions. Dig Liver Dis. 2006;38:39–44.CrossRefGoogle Scholar
  43. 43.
    Ahmad NA, Kochman ML, Brensinger C, et al. Interobserver agreement among endosonographers for the diagnosis of neoplastic versus non-neoplastic pancreatic cystic lesions. Gastrointest Endosc. 2003;58:59–64.CrossRefGoogle Scholar
  44. 44.
    De Jong K, Verlaan T, Dijkgraaf MG, et al. Interobserver agreement for endosonography in the diagnosis of pancreatic cysts. Endoscopy. 2011;43:579–84.CrossRefGoogle Scholar
  45. 45.
    Kim YC, Choi JY, Chung YE, et al. Comparison of MRI and endoscopic ultrasound in the characterization of pancreatic cystic lesions. AJR Am J Roentgenol. 2010;195:947–52.CrossRefGoogle Scholar
  46. 46.
    Adimoolam V, Sanchez MJ, Siddiqui UD, et al. Endoscopic ultrasound identifies synchronous pancreas cystic lesions not seen on initial cross-sectional imaging. Pancreas. 2011;40:1070–2.CrossRefGoogle Scholar
  47. 47.
    Zhong N, Zhang L, Takahashi N, et al. Histologic and imaging features of mural nodules in mucinous pancreatic cysts. Clin Gastroenterol Hepatol. 2012;10:192–8.CrossRefGoogle Scholar
  48. 48.
    Kim KW, Park SH, Pyo J, et al. Imaging features to distinguish malignant and benign branch-duct type intraductal papillary mucinous neoplasms of the pancreas: a meta-analysis. Ann Surg. 2014;259:72–81.CrossRefGoogle Scholar
  49. 49.
    Anand N, Sampath K, Wu BU. Cyst features and risk of malignancy in intraductal papillary mucinous neoplasms of the pancreas: a meta-analysis. Clin Gastroenterol Hepatol. 2013;11:913–21.CrossRefGoogle Scholar
  50. 50.
    Hinoro S, Tani M, Kawai M, et al. The carcinoembryonic antigen level in pancreatic juice and mural nodule size are predictors of malignancy for branch duct type IPMN. Ann Surg. 2012;255:517–22.CrossRefGoogle Scholar
  51. 51.
    Shimizu Y, Yamaue H, Maguchi H, et al. Predictors of malignancy in intraductal papillary mucinous neoplasm of the pancreas: analysis of 310 pancreatic resection patients at multiple high-volume centers. Pancreas. 2013;42:883–8.CrossRefGoogle Scholar
  52. 52.
    Al-Haddad M, Schmidt MC, Sandrasegaran K, et al. Diagnosis and treatment of cystic pancreatic tumors. Clin Gastroenterol Hepatol. 2011;9:635–48.CrossRefGoogle Scholar
  53. 53.
    Tanno S, Nakano Y, Sugiyama Y, et al. Incidence of synchronous and metachronus pancreatic cancer in 168 patients with branch-duct intraductal papillary mucinous neoplasm. Pancreatology. 2010;10:173–8.CrossRefGoogle Scholar
  54. 54.
    Uehara H, Nakaizumi A, Ishikawa O, et al. Development of ductal carcinoma of the pancreas during follow-up of branch-duct intraductal papillary mucinous of the pancreas. Gut. 2008;57:1561–5.CrossRefGoogle Scholar
  55. 55.
    Sawai Y, Yamao K, Chiba T, et al. Development of pancreatic cancers during long-term follow-up of side-branch intraductal papillary mucinous neoplasms. Endoscopy. 2010;42:1077–84.CrossRefGoogle Scholar
  56. 56.
    Miller JR, Meyer JE, Waters JA, et al. Outcome of pancreatic remnant following segmental pancreatectomy for non-invasive intraductal papillary mucinous neoplasm. HPB (Oxford). 2011;13:759–66.CrossRefGoogle Scholar
  57. 57.
    Yoon WJ, Brugge WR. The safety of endoscopic ultrasound-guided fine-needle aspiration of pancreatic cystic lesions. Endosc ultrasound. 2015;4:289–92.CrossRefGoogle Scholar
  58. 58.
    Wang KX, Ben QW, Jin ZD, et al. Assessment of morbidity and mortality associated with EUS-guided FNA: a systematic review. Gastrointest Endosc. 2011;73:283–90.CrossRefGoogle Scholar
  59. 59.
    Early DS, Acosta RD, Chandrasekhara V, et al. Adverse events associated with EUS and EUS with FNA. Gastrointest Endosc. 2013;77:839–43.CrossRefGoogle Scholar
  60. 60.
    Khashab MA, Kim K, Lennon AM, et al. Should we do EUS/FNA on patients with pancreatic cysts? The incremental diagnostic yield of EUS over CT/MRI for prediction of cystic neoplasms. Pancreas. 2013;42:717–21.CrossRefGoogle Scholar
  61. 61.
    Thornton GD, McPhail MJ, Nayagam S, et al. Endoscopic ultrasound guided fine needle aspiration for the diagnosis of pancreatic cystic neoplasms: a meta-analysis. Pancreatology. 2013;13:48–57.CrossRefGoogle Scholar
  62. 62.
    Park W, Wu M, Bowen R, et al. Metabolomic-derived novel cyst fluid biomarkers for pancreatic cysts: glucose and kynurenine. Gastrointest Endosc. 2013;78:295–302.CrossRefGoogle Scholar
  63. 63.
    Zykos T, Pham K, Bowen R, et al. Cyst fluid glucose is rapidly feasible and accurate in diagnosing mucinous pancreatic cysts. Am J Gastroenterol. 2015;110:909–14.CrossRefGoogle Scholar
  64. 64.
    Khalid A, Zahid M, Finkelstein SD, et al. Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study. Gastrointest Endosc. 2009;69:1095–102.CrossRefGoogle Scholar
  65. 65.
    Lee LS, Doyle LA, Houghton J, et al. Differential expression of GNAS and KRAS mutations in pancreatic cysts. JOP. 2014;15:581–6.Google Scholar
  66. 66.
    Yip-Schneider M, Wu H, Dumas R, et al. Vascular endothelial growth factor, a novel and highly accurate pancreatic fluid biomarker for serous pancreatic cysts. J Am Coll Surg. 2014;218:608–17.CrossRefGoogle Scholar
  67. 67.
    Reid MD, Choi H, Balci S, et al. Serous cystic neoplasms of the pancreas: clinicopathologic and molecular characteristics. Semin Diagn Pathol. 2014;31:475–83.CrossRefGoogle Scholar
  68. 68.
    Al-Haddad M, DeWitt J, Sherman S, et al. Performance characteristics of molecular (DNA) analysis for the diagnosis of mucinous pancreatic cysts. Gastrointest Endosc. 2014;79:79–87.CrossRefGoogle Scholar
  69. 69.
    Bhutani MS, Koduru P, Joshi V, et al. EUS-guided needle-based confocal laser endomicroscopy: a novel technique with emerging applications. Gastroenterol Hepatol. 2015;11:235–40.Google Scholar
  70. 70.
    Becker V, Wallace MB, Fockens P, et al. Needle-based confocal endomicroscopy for in vivo histology of intra-abdominal organs: first results in a porcine model (with videos). Gastrointest Endosc. 2010;71:1260–6.CrossRefGoogle Scholar
  71. 71.
    Konda VJ, Aslanian HR, Wallace MB, et al. First assessment of needle-based confocal laser endomicroscopy during EUS-FNA procedures of the pancreas (with videos). Gastrointest Endosc. 2011;74:1049–60.CrossRefGoogle Scholar
  72. 72.
    Konda VJ, Meining A, Jamil LH, et al. A pilot study of in vivo identification of pancreatic cystic neoplasms with needle-based confocal laser endomicroscopy under endosonographic guidance. Endoscopy. 2013;45:1006–13.CrossRefGoogle Scholar
  73. 73.
    Nakai Y, Iwashita T, Park DH, et al. Diagnosis of pancreatic cysts: EUS-guided, through-the-needle confocal laser-induced endomicroscopy and cystoscopy trial: DETECT study. Gastrointest Endosc. 2015;81:1204–14.CrossRefGoogle Scholar
  74. 74.
    Napoléon B, Lemaistre AI, Pujol B, et al. A novel approach to the diagnosis of pancreatic serous cystadenoma: needle-based confocal laser endomicroscopy. Endoscopy. 2015;47:26–32.CrossRefGoogle Scholar
  75. 75.
    Krishna SG, Swanson B, Conwell DL, et al. In vivo and ex vivo needle-based confocal endomicroscopy of intraductal papillary mucinous neoplasm of the pancreas. Gastrointest Endosc. 2015;82:571–2.CrossRefGoogle Scholar
  76. 76.
    Song TJ, Kim JH, Lee SS, et al. The prospective randomized, controlled trial of endoscopic ultrasound-guided fine-needle aspiration using 22G and 19G aspiration needles for solid pancreatic or peripancreatic masses. Am J Gastroenterol. 2010;105:1739–45.CrossRefGoogle Scholar
  77. 77.
    Napoleon B, Alvarez-Sanchez MV, Gincoul R, et al. Contrast-enhanced harmonic endoscopic ultrasound in solid lesions of the pancreas: results of a pilot study. Endoscopy. 2010;42:564–70.CrossRefGoogle Scholar
  78. 78.
    Kitano M, Sakamoto H, Matsui U, et al. A novel perfusion imaging technique of the pancreas: contrast-enhanced harmonic EUS (with video). Gastrointest Endosc. 2008;67:141–50.CrossRefGoogle Scholar
  79. 79.
    De Jong N, Frinking PJ, Bouakaz A, et al. Detection procedures of ultrasound contrast agents. Ultrasonics. 2000;38:87–92.CrossRefGoogle Scholar
  80. 80.
    Kamata K, Kitano M, Omoto S, et al. Contrast-enhanced harmonic endoscopic ultrasonography for differential diagnosis of pancreatic cysts. Endoscopy. 2016;48:35–41.CrossRefGoogle Scholar
  81. 81.
    Fusaroli P, Spada A, Mancino MG, et al. Contrast harmonic echo–endoscopic ultrasound improves accuracy in diagnosis of solid pancreatic masses. Clin Gastroenterol Hepatol. 2010;8:629–34.CrossRefGoogle Scholar
  82. 82.
    Fusaroli P, Kypraios D, Mancino MG, et al. Interobserver agreement in contrast harmonic endoscopic ultrasound. J Gastroenterol Hepatol. 2012;27:1063–9.CrossRefGoogle Scholar
  83. 83.
    Saftoiu A, Dietrich CF, Vilmann P. Contrast-enhanced harmonic endoscopic ultrasound. Endoscopy. 2012;44:612–7.CrossRefGoogle Scholar
  84. 84.
    Yamamoto N, Kato H, Tomoda T, et al. Contrast-enhanced harmonic endoscopic ultrasonography with time-intensity curve analysis for intraductal papillary mucinous neoplasms of the pancreas. Endoscopy. 2016;48:26–34.Google Scholar
  85. 85.
    Ohno E, Hirooka Y, Itoh A, et al. Intraductal papillary mucinous neoplasms of the pancreas: differentiation of malignant and benign tumors by endoscopic ultrasound findings of mural nodules. Ann Surg. 2009;249:628–34.CrossRefGoogle Scholar

Copyright information

© Japanese Society of Gastroenterology 2018

Authors and Affiliations

  1. 1.Departamento de GastroenterologíaHospital MéxicoSan JoséCosta Rica
  2. 2.Service de Gastroenterologie, d’endoscopie et de Cancerologie DigestiveAPHP-Hopital CochinParisFrance

Personalised recommendations